Materiały źródłowe

• #1 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Selection of Therapy for Chronic Lymphocytic Leukemia Treatment must be individualized based on the clinical behavior of the disease. Because this disease is generally not curable, occurs in an older population, and often progresses slowly, it is most often treated in a conservative fashion. […] Treatment of patients with CLL ranges from observation with treatment of infectious, hemorrhagic, or immunological complications to a variety of therapeutic options administered as single agents or combination therapy. In asymptomatic patients, treatment may be deferred until the disease progresses and symptoms occur. […] For patients with progressing CLL, treatment will not be curative in most cases. Selected patients treated with allogeneic stem cell transplant have achieved prolonged disease-free survival (DFS), sometimes exceeding 20 years.

• #1 Chronic Lymphocytic Leukemia (CLL) Treatment Protocols: Treatment Protocols

  https://emedicine.medscape.com/article/2005390-overview

  Treatment protocols for chronic lymphocytic leukemia (CLL) are provided below, including the following: […] Patients with low-risk (formerly Rai stage 0; Binet stage A) CLL, who have no evidence of disease progression or disease-related symptoms should be monitored without therapy. Similarly, most patients with intermediate-risk (formerly Rai stages I and II; Binet stage B) can be monitored without therapy until they have evidence of active disease. Most patients with high-risk (formerly Rai stages III and IV); Binet stage C) CLL benefit from treatment. […] Acalabrutinib with or without obinutuzumab: Acalabrutinib 100 mg PO q12hr, Days 1-28 until disease progression or unacceptable toxicity. […] Venetoclax plus obinutuzumab dosages varies by cycle. […] The combination of chlorambucil with obinutuzumab is approved for previously untreated CLL, but progression-free survival is inferior to that seen with acalabrutinib with or without obinutuzumab.

• #1 Chronic lymphocytic leukemia treatment – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/leukaemia/chronic-lymphocytic-leukaemia/treatment/

  Many people with CLL, particularly in the early stages of disease, have no symptoms and don’t require any treatment. Instead the doctor may recommend an ‘actively monitor’ strategy (sometimes called ‘watch and wait’) involving regular check-ups and blood counts to carefully monitor your health. This strategy may also be appropriate in more advanced stages of CLL if your blood counts remain stable. Treatment usually starts only once the disease begins to progress, or causes troublesome symptoms. Many people with CLL have the disease for years without it causing any problems and some people diagnosed with CLL will never require any treatment. There is a general agreement that most people with advanced stage CLL (Rai III and IV, Binet B and C) will need to be treated. Treatment may involve the use of: chemotherapy, monoclonal antibody therapy, stem cell transplantation, experimental treatments available through clinical trials.

• #1 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  The following clinical factors may be helpful in predicting progression of disease: IGH pathogenic variant, chromosomal abnormalities found by FISH or cytogenetic analysis, beta-2-microglobulin, lymphocyte doubling time. […] The International Workshop on Chronic Lymphocytic Leukemia defines symptomatic or progressive CLL as having the following signs and symptoms: evidence of progressive marrow failure, massive splenomegaly, massive lymph nodes, progressive lymphocytosis, autoimmune complications, symptomatic or functional extranodal involvement. […] The following regimens are considered first-line treatment approaches for patients with CLL who are experiencing symptomatic progression: Bruton tyrosine kinase (BTK) inhibitors (acalabrutinib, zanubrutinib, or ibrutinib), Venetoclax with initial use of obinutuzumab or rituximab, Bendamustine and rituximab (BR), Fludarabine, cyclophosphamide, and rituximab (FCR), BTK inhibitor plus venetoclax.

• #1 Chronic Lymphocytic Leukemia (CLL) Treatment & Management: Approach Considerations, Biologic Regimens and Chemotherapy, Transplantation

  https://emedicine.medscape.com/article/199313-treatment

  Patients with chronic lymphocytic leukemia (CLL) with a low Binet or Rai stage who are asymptomatic should not be offered treatment. Patients with stable low-stage CLL require only periodic follow-up. In multiple studies and a meta-analysis, early initiation of chemotherapy in such cases has failed to show benefit; indeed, it may increase mortality. […] Guidelines from the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) provide clinical and laboratory criteria for initiation of primary, second-line, and subsequent-line treatment. […] Treatment is indicated for patients whose CLL progresses or who present with symptomatic disease. The iwCLL guidelines define symptomatic or active disease, which comprise the criteria for starting treatment, by the following: weight loss of at least 10% over 6 months, extreme fatigue, fever of at least 38.0C for 2 or more weeks with no evidence of infection, night sweats for at least 1 month with no evidence of infection, progressive marrow failure, autoimmune anemia or thrombocytopenia not responding to glucocorticoids, progressive or symptomatic splenomegaly, or massive splenomegaly, symptomatic or massive lymphadenopathy, progressive lymphocytosis, and symptomatic extranodal involvement, including in the spine.

• #1 Chronic Lymphocytic Leukemia Treatment (PDQ®) – PDQ Cancer Information Summaries – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK66035/

  Treatment of patients with CLL ranges from observation with treatment of infectious, hemorrhagic, or immunological complications to a variety of therapeutic options administered as single agents or combination therapy. In asymptomatic patients, treatment may be deferred until the disease progresses and symptoms occur. […] A meta-analysis of randomized trials showed no survival benefit for immediate versus delayed therapy for patients with early-stage disease. […] For patients with progressing CLL, treatment will not be curative in most cases. Selected patients treated with allogeneic stem cell transplant have achieved prolonged disease-free survival (DFS), sometimes exceeding 20 years. […] The following clinical factors may be helpful in predicting progression of disease: IGH pathogenic variant, chromosomal abnormalities found by FISH or cytogenetic analysis, beta-2-microglobulin, lymphocyte doubling time.

• #1 First-line therapy for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/treatment/first-line-therapy

  The most common treatments used as first-line therapy for chronic lymphocytic leukemia (CLL) are targeted therapy and chemoimmunotherapy. […] Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them to stop the growth and spread of cancer. Chemoimmunotherapy combines chemotherapy with monoclonal antibodies, which are a type of targeted therapy. Chemotherapy uses drugs to destroy cancer cells. […] First-line therapy if you have CLL that has a 17p chromosome deletion (the short arm „p” of chromosome 17 is missing) or a TP53 gene mutation (the TP53 gene has mutated, or changed) is usually targeted therapy. […] First-line therapy if you have CLL that doesn’t have a 17p chromosome deletion or a mutation to the TP53 gene is targeted therapy or chemoimmunotherapy.

• #1 Current and future treatment strategies in chronic lymphocytic leukemia | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-021-01054-w

  Treatment decisions for patients with chronic lymphocytic leukemia (CLL) are dependent on symptoms and classification into high-, medium-, or low-risk categories. […] Promising results from multiple clinical trials show emerging therapies targeting Burton tyrosine kinase, B-cell leukemia/lymphoma 2, and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta result in better outcomes and prolonged progression-free survival for patients both with and without certain high-risk aberrations. […] Favorable outcomes using these novel oral targeted therapies, either alone or in combination with other treatments such as anti-CD20 antibodies, has led to their use almost entirely supplanting chemoimmunotherapy in the treatment of CLL. […] Novel, oral, targeted therapies have almost entirely supplanted chemoimmunotherapy in the treatment of CLL.

• #1 Chronic Lymphocytic Leukemia (CLL) Treatment & Management: Approach Considerations, Biologic Regimens and Chemotherapy, Transplantation

  https://emedicine.medscape.com/article/199313-treatment

  The current focus in CLL is on targeted therapies in various combinations, which are discussed below. These have already been proven superior to chemoimmunotherapy. […] Bruton tyrosine kinase (BTK) leads to downstream activation of B-cell survival pathways, including nuclear factor-kB (NF-kB), which helps prevent apoptosis and promotes survival of B-cells. BTK inhibitors block this pathway and therefore promote destruction of the leukemic cells. […] Ibrutinib was approved for CLL in patients who had received at least one previous therapy. […] In 2016, the FDA further expanded the indication for ibrutinib to include treatment-naive patients. […] The CLL12 trial, published in 2022, showed that ibrutinib prolonged survival in Binet stage A patients who had not received prior treatment for CLL.

• #1 CLL and SLL Treatment | IMBRUVICA® (ibrutinib)

  https://www.imbruvica.com/cll

  IMBRUVICA has helped many adults with CLL/SLL live longer* […] In one clinical trial of 269 people aged 65 and older with CLL or SLL who had not been treated before, people who took IMBRUVICA had a 56% lower risk of death compared to those taking a chemotherapy (chlorambucil). With a median follow-up of approximately 28 months, 8% of IMBRUVICA patients died compared to 16% taking a chemotherapy. […] IMBRUVICA works differently from chemotherapy. This once-daily, oral medication blocks a protein in B cells called Bruton’s tyrosine kinase, or BTK. […] IMBRUVICA is a prescription medicine used to treat adults with: Chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) […] IMBRUVICA may cause serious side effects, including: Bleeding problems (hemorrhage) are common during treatment with IMBRUVICA and can also be serious and may lead to death. […] IMBRUVICA is a prescription medicine used to treat: Adults with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).

• #1 Chronic Lymphocytic Leukemia (CLL) Treatment Protocols: Treatment Protocols

  https://emedicine.medscape.com/article/2005390-overview

  In January 2023, FDA granted accelerated approval for zanubrutinib to treat patients with CLL or SLL. […] Fludarabine-based therapy: FCR (fludarabine, cyclophosphamide, and rituximab) remains a recommended first-line treatment for fit young patients (60 years) with IGVH hypermutation without the del (17p)/TP53 mutation, as long-term remissions have been reported in this setting. […] For CLL/SLL without del(17p)/TP53 mutation, options include the following: Acalabrutinib 100 mg PO q12hr, Days 1-28 until disease progression or unacceptable toxicity. […] The BR (bendamustine and rituximab) regimen is used as second- or third-line therapy in patients 65 y and patients 65 y with significant comorbidities. […] Alemtuzumab (Campath) has been approved for use in CLL and has shown superior response rates compared with chlorambucil.

• #1 Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Review – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36943212/

  Chronic lymphocytic leukemia (CLL), defined by a minimum of 5 109/L monoclonal B cells in the blood, affects more than 200 000 people and is associated with approximately 4410 deaths in the US annually. […] Patients with symptomatic disease who have bulky or progressive lymphadenopathy or hepatosplenomegaly and those with a low neutrophil count, anemia, or thrombocytopenia and/or symptoms of fever, drenching night sweats, and weight loss (B symptoms) should be offered treatment. For these patients, first-line treatment consists of a regimen containing either a covalent Bruton tyrosine kinase (BTK) inhibitor (acalabrutinib, zanubrutinib, or ibrutinib) or a B-cell leukemia/lymphoma 2 (BCL2) inhibitor (venetoclax). […] The covalent BTK inhibitors are typically used indefinitely. […] Venetoclax is prescribed in combination with obinutuzumab, a monoclonal anti-CD20 antibody, in first-line treatment for 1 year (overall survival, 82% at 5-year follow-up).

• #1 Chronic lymphocytic leukemia treatment algorithm 2022 | Blood Cancer Journal

  https://www.nature.com/articles/s41408-022-00756-9

  The CLL14 trial compared fixed duration venetoclax-obinutuzumab (venetoclax administered for 12 cycles; each cycle=28 days) to chlorambucil-obinutuzumab in 432 previously untreated CLL patients (median age=72 years, median cumulative illness rating scale [CIRS] score=8, del17p in 8%). After a median follow-up of 52 months, the estimated 4-year PFS was longer with venetoclax-obinutuzumab compared to chlorambucil-obinutuzumab (74% vs. 35%, P0.0001), although no difference in OS was noted. […] Venetoclax-based treatment represents the standard of care for patients progressing after BTKi.

• #1 Chronic Lymphocytic Leukemia – Treatment Options – Messino Cancer Centers

  https://messinocancercenters.com/resource/chronic-lymphocytic-leukemia/chronic-lymphocytic-leukemia-treatment-options/

  Chemotherapy is the use of drugs to destroy cancer cells, usually by ending the cancer cells ability to grow and divide. Common drugs for CLL include Bendamustine, Fludarabine, Pentostatin, Cladribine, Chlorambucil, and Cyclophosphamide. The side effects of chemotherapy depend on the individual and the dose used, but they can include fatigue, risk of infection, nausea and vomiting, hair loss, loss of appetite, and diarrhea. […] Targeted therapy is a treatment that targets the leukemias specific genes, proteins, or the tissue environment that contributes to its growth and survival. This type of treatment blocks the growth and spread of leukemia cells while limiting damage to healthy cells. Monoclonal antibodies for CLL include Rituximab, Ofatumumab, Obinutuzumab, and Venetoclax. Kinase inhibitors for CLL are fairly new and may only be available for patients with CLL that has returned or worsened or in clinical trials.

• #1 How RITUXAN® (rituximab) Works | Chronic Lymphocytic Leukemia (CLL)

  https://www.rituxan.com/cll/results/goals-of-treatment.html

  When you don’t have symptoms and your CLL does not seem to be getting worse, close monitoring is usually preferred over treatment. This is often referred to as watch and wait. When symptoms appear or worsen, treatment aims to stop the CLL from progressing. […] Though there is no cure for CLL, some goals of treatment are to: Relieve symptoms, Keep the disease from advancing, Get the disease into remission. […] If your doctor says you need treatment, there are many options to help manage your condition. Your CLL can be treated in a number of ways, including antibody therapy and/or chemotherapy. Often, doctors will combine the 2 types of treatment. […] RITUXAN is a prescription medicine used to treat adults with Chronic Lymphocytic Leukemia (CLL): with the chemotherapy medicines fludarabine and cyclophosphamide.

• #1 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Ofatumumab is a humanized anti-CD20 monoclonal antibody. […] Relatively low doses of radiation therapy can be administered for lymphadenopathy that causes problems due to size or encroachment on adjacent organs. […] Alemtuzumab is no longer available commercially in the United States for neoplastic indications but can be obtained from the pharmaceutical company on a compassionate-use basis.

• #1 Chronic Lymphocytic Leukemia (CLL) Treatment & Management: Approach Considerations, Biologic Regimens and Chemotherapy, Transplantation

  https://emedicine.medscape.com/article/199313-treatment

  Unfortunately, hypertension has proved to be an extremely common adverse event in patients taking ibrutinib. […] Resistance to ibrutinib has been reported, and the mechanisms of resistance are only partially understood. […] Acalabrutinib is an irreversible BTK inhibitor and is more selective than ibrutinib. […] Venetoclax is a BH3 mimetic that is a selective inhibitor of the B-cell lymphoma 2 (Bcl-2) regulator protein, an antiapoptotic protein. […] The following monoclonal antibodies are approved for use in CLL: Obinutuzumab, Ofatumumab, Alemtuzumab. […] Alemtuzumab has been shown to be effective in treating CLL with high-risk genetic markers, including the p53 mutations. […] The combination of obinutuzumab with chlorambucil was found to be superior to rituximab/chlorambucil in a study of treatment-naive CLL patients.

• #1 Chronic lymphocytic leukemia treatment algorithm 2022 | Blood Cancer Journal

  https://www.nature.com/articles/s41408-022-00756-9

  Management is guided by risk-stratification, while including supportive care is necessary for all patients with a CLL diagnosis. […] Patients in the high- and very high-risk CLL-IPI group (~30% of all newly diagnosed patients, the median time to first therapy 2.1 years and 0.7 years, respectively) should be monitored for disease progression every 36 months. Patients with high- and very high-risk CLL may be offered treatment in early intervention clinical trials. […] Given the consistent observations of improved progression-free survival (PFS) and OS with the use of novel agents compared to CIT, we no longer recommend the routine use of FCR (fludarabine, cyclophosphamide, rituximab), BR (bendamustine, rituximab), or chlorambucil in the frontline management of CLL. […] Venetoclax- and BTKi-based treatments are both excellent options for patients without a TP53 aberration and we favor either over CIT in this setting as well, regardless of IGHV mutation status.

• #1 Current and future treatment strategies in chronic lymphocytic leukemia | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-021-01054-w

  In addition to monotherapy with these oral targeted agents, combinations with other types of therapies are also common. […] Less-favorable CLL prognostic markers such as del(17p) or TP53 dysfunction do not lead to long-term remissions with standard chemoimmunotherapy and patients with these disease features are best treated with novel agents. […] BTK inhibitors have become a recommended first-line treatment option in patients with CLL, whether or not they have TP53 dysfunction, and whether or not their disease has relapsed or become refractory on other treatments. […] Patients who were considered high-risk because of del(17p), del(11q), unmutated IGHV, or TP53 dysfunction when chemotherapy was the only available first-line therapy, have much-improved outcomes with BTK-inhibitor therapy.

• #1 CLL / SLL Treatment and Research – CLL Society

  https://cllsociety.org/treatment-and-research/

  New improved medications and drug combinations are constantly improving outcomes. […] Research drives success. […] CLL / SLL is not a solved problem and never will be without new treatments and more research. […] Ambassador Program for CLL Patients. […] For individuals living with CLL / SLL and considering various treatment options, CLL Society’s Ambassador Program can connect you with a fellow CLL patient who has received the treatment. Connect with an Ambassador. […] Frontline combination acalabrutinib, venetoclax, and obinutuzumab produces high rates of undetectable measurable residual disease (uMRD) in patients with CLL, including those with high-risk features. […] Combination therapies are increasingly being studied in the hopes of getting patients with chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) into deeper remissions and allowing for time-limited therapy.

• #1 Chronic Lymphocytic Leukemia (CLL) Treatment Protocols: Treatment Protocols

  https://emedicine.medscape.com/article/2005390-overview

  Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase that is indicated for CLL in patients who are treatment-naive or have been previously treated. […] The PI3K inhibitors idelalisib and duvelisib are approved for treatment of relapsed CLL, but have high rates of adverse effects (ie, infections and autoimmune complications). […] Lenalidomide, with or without rituximab, is recommended for refractory or relapsed CLL. […] Treatment options include any of the following: Ibrutinib 420 mg once daily until disease progression; BR regimen; Chlorambucil with or without prednisone; Reduced-dose FCR; Alemtuzumab. […] Treatment recommendations for patients with del (17p) include Acalabrutinib with or without obinutuzumab, Venetoclax with obinutuzumab, and Zanubrutinib. […] The presence of any of the following indications in patients with localized SLL or advanced disease with del (17p) should lead to treatment with chemotherapy or chemoimmunotherapy.

• #1 First-line therapy for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/treatment/first-line-therapy

  If the IGHV gene is unmutated (the IGHV gene has not changed) and you are younger than 65 years old and in good overall health, you will be offered targeted therapy for first-line therapy. […] If the IGHV gene is mutated and you are younger than 65 years old and in good overall health, the most common first-line therapy is FCR, which is a type of chemoimmunotherapy. […] If the IGHV gene is mutated and you are older than 65 or your overall health is poor, the first-line therapy is either targeted therapy or chemoimmunotherapy.

• #1 Typical Treatment of CLL | American Cancer Society

  https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/treating/treatment-by-risk-group.html

  There are many options for first-line treatment of CLL, including targeted drugs, chemotherapy, immunotherapy, and different combinations of these. […] Some of the more common options include: A BTK inhibitor such as ibrutinib (Imbruvica), zanubrutinib (Brukinsa), or acalabrutinib (Calquence), either alone or with an anti-CD20 immunotherapy such as obinutuzumab (Gazyva) or rituximab (Rituxan, other brand names). […] For people whose CLL cells do not have a deletion in chromosome 17 or a TP53 gene mutation, another option might be chemoimmunotherapy, such as: Fludarabine, cyclophosphamide, and rituximab (FCR). […] It’s not common, but some people who have very high-risk CLL may be referred for a stem cell transplant (SCT) early in treatment. […] If the first treatment for CLL is no longer working, or if the leukemia comes back, another type of treatment often helps.

• #1 Treatments for chronic lymphocytic leukemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/chronic-lymphocytic-leukemia-cll/treatment

  First-line therapies used to treat chronic lymphocytic leukemia (CLL) are targeted therapy and chemoimmunotherapy. […] Treatments for relapsed or refractory chronic lymphocytic leukemia (CLL) include targeted therapy, chemoimmunotherapy and a stem cell transplant. […] Targeted therapy uses drugs to target specific molecules on cancer cells. Chronic lymphocytic leukemia (CLL) is usually treated with targeted therapy. […] Chemoimmunotherapy combines chemotherapy and targeted therapy drugs. Chronic lymphocytic leukemia (CLL) is sometimes treated with chemoimmunotherapy. […] A stem cell transplant replaces stem cells. Chronic lymphocytic leukemia (CLL) is sometimes treated with a stem cell transplant.

• #1 What are the Treatments for CLL? – HealthTree for Chronic Lymphocytic Leukemia

  https://healthtree.org/cll/community/what-are-the-treatments-for-cll

  If you have previously taken and become intolerant to venetoclax and a BTK inhibitor, there are other treatment options. […] Pirtobrutinib (Jaypirca, Eli Lilly): A non-covalent BTK inhibitor that binds to the CLL cells in a different way than covalent BTK inhibitors, allowing the medicine to inhibit CLL progression despite prior resistance to covalent BTK inhibitors. […] Liso-cel (Breyanzi, BMS): A CAR T-cell therapy that works by re-engineering your T-cells to more effectively kill CLL cells. […] Allogeneic stem cell transplant: You receive an infusion of donor stem cells (cells capable of forming all other types of blood cells).

• #1 Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Review – PubMed

  https://pubmed.ncbi.nlm.nih.gov/36943212/

  In patients with multiple relapses, chimeric antigen receptor T-cell (CAR-T) therapy with lisocabtagene maraleucel was associated with a 45% complete response rate. The only potential cure for CLL is allogeneic hematopoietic cell transplant, which remains an option after use of targeted agents. […] Highly effective novel targeted agents include BTK inhibitors such as acalabrutinib, zanubrutinib, ibrutinib, and pirtobrutinib or BCL2 inhibitors such as venetoclax.

• #1 Chronic Lymphocytic Leukemia (CLL) – Hematology and Oncology – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/hematology-and-oncology/leukemias/chronic-lymphocytic-leukemia-cll

  Given the advent of targeted therapy for use in upfront treatment of CLL, several studies have examined a „time limited” approach to treatment. […] Relapsed or refractory CLL should be confirmed histologically before restarting treatment. […] In patients who received upfront chemoimmunotherapy, treatment with a Btk inhibitor can improve response rate and progression-free survival in relapsed or refractory CLL. […] Monotherapy with an anti-CD20 monoclonal antibody (rituximab, ofatumumab, obinutuzumab) may transiently palliate symptoms. […] Allogeneic stem cell transplantation should be considered for patients who are fit and whose leukemia is refractory to novel combinations of targeted therapies with immunotherapies and emerging cellular therapies. […] Palliative irradiation may be given to areas of lymphadenopathy or for liver and spleen involvement that does not respond to chemotherapy.

• #1 Chronic Lymphocytic Leukemia | Conditions | UCSF Health

  https://www.ucsfhealth.org/conditions/chronic-lymphocytic-leukemia

  The remission rate and length of remission are increased by adding a monoclonal antibody, Rituximab also used to treat lymphoma to fludarabine. […] Allogeneic stem cell transplantation, also called bone and marrow transplantation (BMT), can be used to potentially cure CLL. However, this therapy is only used to treat the occasional young patient with aggressive CLL, since most patients with CLL live so long that the risk of transplant can seldom be justified. […] UCSF is dedicated to improving outcomes for CLL patients through the use of investigational therapies and clinical research trials. Clinical trials currently available to UCSF patients include Flavopiridol for CLL cases that don’t respond to standard treatment.

• #1 Chronic Lymphocytic Leukemia – Treatment Options – Messino Cancer Centers

  https://messinocancercenters.com/resource/chronic-lymphocytic-leukemia/chronic-lymphocytic-leukemia-treatment-options/

  A bone marrow transplant is a medical procedure in which bone marrow that contains leukemia is replaced by highly specialized cells, called hematopoietic stem cells, that develop into healthy bone marrow. There are 2 types of stem cell transplantation depending on the source of the replacement blood stem cells: allogeneic (ALLO) and autologous (AUTO). ALLO is the type of transplant used for treating CLL and is typically considered for younger patients either when the standard treatments have not worked well or the patient has a high risk of the CLL returning more quickly. […] Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time. Radiation therapy is not often used to treat CLL because the disease is located throughout the body. However, radiation therapy can be very helpful to shrink an enlarged spleen or swollen lymph nodes and relieve certain symptoms.

• #1 Treatment for chronic lymphocytic leukaemia (CLL) | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/chronic-lymphocytic-leukaemia-cll/treatment

  You may not need treatment straight away if you have early stage CLL and you don’t have symptoms. […] The main treatment for CLL is targeted cancer drugs. […] The main treatments for chronic lymphocytic leukaemia are targeted cancer drugs. You might have a combination of a targeted cancer drug with other anti cancer treatments. […] You might not need treatment straight away, or never need it. Doctors monitor you with regular check ups and tests. They call this 'watch and wait’, 'active monitoring’, or 'active surveillance’. […] When CLL comes back it is called a relapse. You might need more treatment. […] Treatment for CLL can be as tablets or as an injection into a vein as a drip (intravenously). […] Supportive treatments can help to either prevent or control these problems. […] A stem cell transplant isn’t a common treatment for CLL. You usually have stem cells from another person (a donor). […] Rarely, your doctor might suggest an operation to remove your spleen if you have chronic lymphocytic leukaemia. […] How often you have check ups will depend on whether you are having treatment or not and how you are feeling.

• #1 Chronic Lymphocytic Leukemia (CLL): Treatment Choices | Saint Luke’s Health System

  https://www.saintlukeskc.org/health-library/chronic-lymphocytic-leukemia-cll-treatment-choices

  There are many treatment choices for chronic lymphocytic leukemia (CLL). Which one may work best for you? It depends on a number of factors. These include the stage of your CLL and your test results. Other factors include if the CLL is causing symptoms, as well as your age, overall health, and what side effects you’ll find acceptable. […] Different types of treatment have different goals. Here are some of the common types of treatment and their goals for people with CLL. […] The goal of chemotherapy (chemo) for CLL is to kill cancer cells and keep them from growing and dividing. […] Targeted therapy is often the first treatment for CLL. […] Sometimes stem cell transplant is needed to treat CLL that doesn’t respond to regular treatment or comes back after treatment. […] This treatment uses strong X-rays to kill cancer cells or prevent their growth. It’s not often used to treat CLL, but may be helpful in certain cases. […] A splenectomy is a surgery to remove your spleen. In rare cases, this may be done to treat CLL. It doesn’t cure the leukemia, but it can improve symptoms. […] Researchers are always finding new ways to treat CLL. These new methods are tested in clinical trials.

• #1 First treatment for chronic lymphocytic leukaemia (CLL) | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/chronic-lymphocytic-leukaemia-cll/treatment/first-treatment

  Your doctor considers several factors when deciding about treatment, including: […] Some people aren’t well enough to have the standard treatment. There are other treatment options available. Most treatments have side effects and some drugs might be more suitable for you than others. Your doctor will decide which drug is best for you, to lower the risk of treatment complications. […] If your CLL doesn’t have a change (mutation) in the TP53 gene […] You usually have treatment with targeted cancer drugs such as: […] You can read more about these different treatments and their side effects on our drug pages. […] You might have other treatments to treat symptoms of CLL, or to prevent problems caused by the leukaemia. […] Other treatments you might have for CLL include: […] You don’t often have radiotherapy for CLL. But your doctor might suggest it if your spleen is very swollen (enlarged) or causing you symptoms.

• #1 Chronic Lymphocytic Leukemia (CLL) Treatment Protocols: Treatment Protocols

  https://emedicine.medscape.com/article/2005390-overview

  Consider ID prophylaxis with trimethoprim/sulfamethoxazole and acyclovir/valacyclovir for patients receiving idelalisib, fludarabine, or alemtuzumab. […] Immune thrombocytopenia and autoimmune hemolytic anemia can occur with CLL and should be treated with immunosuppression. […] Complete response is defined as follows: All lymph nodes smaller than 1 cm; Normal liver and spleen; No constitutional symptoms; Leukocyte counts 1500/mm3; Normal circulating B lymphocytes; Platelet counts 100,000/mm3; Hemoglobin level 11 g/dL; Normocellular bone marrow with 30% lymphocytes and no B-lymphoid nodules. […] Partial response is defined as follows: Decrease in lymph nodes by 50% or more; Liver and spleen sizes decreased by 50% or more; Any constitutional symptoms; Leukocyte counts 1500/mm3 or 50% improvement; Circulating B lymphocytes decreased by 50% or more; Platelet counts 100,000/mm3 or 50% increase from baseline; Hemoglobin level 2 g/dL from baseline; Hypocellular bone marrow or 30% lymphocytes or B-lymphoid nodules.

• #1 Chronic lymphocytic leukemia treatment – Leukaemia Foundation

  https://www.leukaemia.org.au/blood-cancer/types-of-blood-cancer/leukaemia/chronic-lymphocytic-leukaemia/treatment/

  A range of supportive therapies are available to treat symptoms of CLL. These include antibiotics to prevent and treat infections, and blood and platelet transfusions to restore levels of red cells and platelets. Steroids (corticosteroids) are commonly used in combination with the chemotherapy regimens prescribed to treat CLL. For a very small number of people with CLL (mainly younger people with aggressive disease) a stem cell transplant may be used. This treatment, while offering the prospect of a cure, carries serious risks and is usually only offered if your doctor feels it will be of most benefit to you.

• #1 Chronic lymphocytic leukemia – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/chronic-lymphocytic-leukemia/symptoms-causes/syc-20352428

  Chronic lymphocytic leukemia most commonly affects older adults. There are treatments to help control the disease. […] Explore Mayo Clinic studies testing new treatments, interventions and tests as a means to prevent, detect, treat or manage this condition. […] Your doctor might recommend regular immunoglobulin infusions. […] A small number of people with chronic lymphocytic leukemia may develop a more aggressive form of cancer called diffuse large B-cell lymphoma. Doctors sometimes refer to this as Richter’s syndrome. […] People with chronic lymphocytic leukemia have an increased risk of other types of cancer, including skin cancer and cancers of the lung and the digestive tract.

• #1 Content – Health Encyclopedia – University of Rochester Medical Center

  https://www.urmc.rochester.edu/encyclopedia/content.aspx?contenttypeid=34&contentid=BCLLT11

  You may also get an infection more easily. […] Other side effects include: Nausea, Swelling, Feeling very tired (fatigue), Headache, Constipation or diarrhea, Low blood cell counts, which can increase the risk of not only infection but also bleeding and bruising. […] These medicines can also cause tumor lysis syndrome.

• #1 Chronic Lymphocytic Leukemia Treatment – NCI

  https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq

  Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. […] Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. […] Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. […] New types of treatment are being tested in clinical trials. […] Treatment for chronic lymphocytic leukemia may cause side effects. […] Patients may want to think about taking part in a clinical trial. […] Patients can enter clinical trials before, during, or after starting their cancer treatment. […] Follow-up care may be needed.

• #1 How We Treat Chronic Lymphocytic Leukemia | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/chronic-lymphocytic-leukemia/treatment

  Patients have the opportunity to participate in clinical trials for new therapies for all phases of CLL, including advanced CLL. […] The goal of these trials is to extend the duration of patients’ responses to treatment, and to improve outcomes. […] Many new therapies are improving treatment outcomes for patients with CLL, and researchers at our Center for Chronic Lymphocytic Leukemia are driving much of the progress being made. […] Current trials are combining agents to define new CLL regimens for future patients. […] If you need to be hospitalized during your care, or if you undergo stem cell transplantation, you will be admitted to Brigham and Women’s Hospital (BWH) or the Dana-Farber Inpatient Hospital located within BWH. […] We believe there is value in patients with suspected or diagnosed CLL receiving a second opinion.

• #1 Help with Side Effects of Chronic Lymphocytic Leukemia (CLL) Treatment

  https://www.healthline.com/health/cancer/8-ways-to-manage-side-effects-of-cll-treatment

  Chemotherapy and immunotherapies for CLL can cause side effects. Treatments can damage the lining of your mouth, throat, stomach, and intestines. They may also damage your immune system and increase the risk of infection. […] Treatments for CLL can effectively destroy cancer cells, but they can also damage healthy cells. Chemotherapy drugs most often lead to side effects, but targeted therapies and immunotherapies can cause side effects as well. […] These treatments may include chemotherapy, radiation therapy, or other targeted procedures and immunotherapies. Bone marrow transplants, blood transfusions, and spleen removal surgery may also be options. […] All these treatments bring their own sets of risks and side effects. […] Side effects can happen with any of the treatments for CLL, but everyone’s experience will be different.

• #1 Chronic Lymphocytic Leukemia Treatment (PDQ®) – PDQ Cancer Information Summaries – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK66035/

  In summary, these trials establish the use of venetoclax with obinutuzumab or rituximab, or the use of ibrutinib, acalabrutinib, or zanubrutinib as first-line therapy in patients with previously untreated CLL. A lower rate of atrial fibrillation occurs with acalabrutinib or zanubrutinib than with ibrutinib. […] Unlike ibrutinib or acalabrutinib, which are given continuously until relapse, venetoclax may be stopped after 12 months, with durable maintenance of remission.

• #1 Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

  https://www.mdpi.com/1999-4923/16/1/55

  Venetoclax: It is a BCL-2 inhibitor (BCL-2i) that binds directly to the BH3 binding site. […] New targeted therapies have led to a decline in the utilization of allogeneic hematopoietic stem cell transplantation (alloHCT) in CLL patients. […] When choosing a patient for alloHCT, factors such as the patient’s functional status, age, comorbidities, donor availability, status of del17p and TP53mut, prior treatment history and response duration, the level of response to the current therapy, and the availability of alternative treatment options should also be considered. […] Another therapy that is under study for refractory patients is CAR-T. […] Aberrations in TP53 have been acknowledged to impart an unfavorable prognosis concerning response rate, PFS, and OS, especially with CIT but also with novel agents.

• #1 Current and future treatment strategies in chronic lymphocytic leukemia | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-021-01054-w

  Given the current treatment landscape, venetoclax plus obinutuzumab has emerged as another important first-line treatment option, as well as the most obvious first-line treatment, for patients with TP53 dysfunction and unmutated IGHV who are not suitable candidates for BTK-inhibitor monotherapy. […] There are currently 2 PI3K inhibitors approved for the treatment of CLL. […] Given the toxicity issues, treatment with idelalisib has been limited in comparison to BTK inhibitor treatment. […] New therapies and treatment strategies should not only aim to improve tolerability and to overcome the development of resistance, but also to extend remission with duration-limited approaches, regardless of risk factors. […] Next-generation BTK, BCL-2, and PI3K inhibitors that may address shortcomings related to tolerability and resistance are in development. […] Research into the development of novel therapies or drug combinations with the goal of offering a finite treatment option is needed.

• #1 Chronic lymphocytic leukemia treatment algorithm 2022 | Blood Cancer Journal

  https://www.nature.com/articles/s41408-022-00756-9

  The treatment landscape for patients with chronic lymphocytic leukemia (CLL) has changed considerably with the introduction of very effective oral targeted therapies (such as Bruton tyrosine kinase inhibitors and venetoclax) and next-generation anti-CD20 monoclonal antibodies (such as obinutuzumab). These agents lead to improved outcomes in patients with CLL, even among those with high-risk features, such as del17p13 or TP53 mutation and unmutated immunoglobulin heavy chain (IGHV) genes. […] Selecting the right treatment for the right patient requires consideration of disease characteristics and prior treatment sequence, as well as patient preferences and comorbidities. […] The CLL-International Prognostic Index (CLL-IPI) remains the best-validated tool in predicting the time to first therapy among previously untreated patients, which guides selection for early intervention efforts.

• #1 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  In the relapsed setting, venetoclax showed similar efficacy and safety even after previous therapy with ibrutinib or idelalisib. […] The same regimens considered for first-line therapy for patients with CLL can be readministered in a sequential fashion. […] Autologous T cells can be modified by viral vectors to incorporate antigen receptor specificity for the B-cell antigen CD19 and then infused into previously treated patients. […] Lenalidomide is an oral immunomodulatory agent with response rates of more than 50%, with or without rituximab, for patients with previously treated and untreated disease. […] In a prospective randomized trial, 241 previously untreated patients younger than 66 years with advanced-stage disease received induction therapy with a CHOP-based regimen followed by fludarabine.

• #1 Chronic Lymphocytic Leukemia Treatment – NCI

  https://www.cancer.gov/types/leukemia/patient/cll-treatment-pdq

  Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). […] Treatment options depend on: […] The treatment of asymptomatic chronic lymphocytic leukemia (CLL) may include watchful waiting. […] The treatment of symptomatic or progressive chronic lymphocytic leukemia (CLL) may include the following: […] The treatment of recurrent or refractory chronic lymphocytic leukemia (CLL) may include therapies and clinical trials. […] There are different types of treatment for patients with chronic lymphocytic leukemia (CLL). […] The following types of treatment are used: […] Watchful waiting is closely monitoring a patient’s condition without giving any treatment until signs or symptoms appear or change. […] Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells.

• #2 CLL Treatment Guidelines for Healthcare Professionals

  https://www.lymphoma.ca/resources/healthcare-professionals/treatment-guidelines/chronic-lymphocytic-leukemia-treatment/

  Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in North America. In 2018, Lymphoma Canada led a project, which resulted in the development of the first unified national guideline for the front-line treatment of CLL. […] In 2022, Lymphoma Canada and a group Canadian clinical experts updated these guidelines, which include new and innovative therapeutic options for CLL patients in the frontline setting. Recommendations were provided based on review of available evidence for the first-line treatment of CLL. […] Following the recent publication of Canadian evidence-based guidelines for frontline treatment of chronic lymphocytic leukemia (CLL), the same group of clinicians developed guidelines for CLL in the relapsed/refractory (R/R) setting. The treatment of R/R CLL has changed significantly in the past few years, with many novel therapeutics available to hematologists across the country. These guidelines aim to standardize the management of CLL in the relapsed/refractory setting, using the best evidence currently available.

• #2 Chronic Lymphocytic Leukemia Treatment (PDQ®) – PDQ Cancer Information Summaries – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK66035/

  This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of chronic lymphocytic leukemia. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions. […] Treatment of patients with chronic lymphocytic leukemia (CLL) must be individualized based on the clinical behavior of the disease. Because this disease is generally not curable, occurs in an older population, and often progresses slowly, it is most often treated in a conservative fashion. […] In older trials with data collected from the 1970s through the 1990s, the median survival for all patients ranged from 8 to 12 years. However, with the introduction of the B-cell receptor inhibitors and targeting of BCL2, the median survival for all patients has not been reached with over 10 years of follow-up.

• #2 Typical Treatment of CLL | American Cancer Society

  https://www.cancer.org/cancer/types/chronic-lymphocytic-leukemia/treating/treatment-by-risk-group.html

  Treatment options for chronic lymphocytic leukemia (CLL) can vary based on factors such as whether the leukemia is causing symptoms or other problems, whether the leukemia cells have certain gene or chromosome changes, and a person’s age and overall health. […] Doctors often advise waiting to treat chronic lymphocytic leukemia (CLL) until the leukemia progresses or causes bothersome symptoms. […] This might be called the watch-and-wait approach, watchful waiting, active surveillance, or observation. This is a standard approach for most people with early-stage CLL who dont have symptoms. […] If you need treatment for your CLL, several factors are important. […] Your cancer care team will consider your age and overall health. They will also consider certain changes in your leukemia cells and how those changes could help predict your outlook (prognosis). This includes whether the leukemia cells have a deletion in chromosome 17, a TP53 gene mutation, or an unmutated version of the IGHV gene.

• #2 Chronic Lymphocytic Leukemia Treatment (PDQ®) – PDQ Cancer Information Summaries – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK66035/

  The International Workshop on Chronic Lymphocytic Leukemia defines symptomatic or progressive CLL as having the following signs and symptoms: evidence of progressive marrow failure, massive progressive or symptomatic splenomegaly, massive lymph nodes, progressive lymphocytosis, autoimmune complications, and symptomatic or functional extranodal involvement. […] Despite many therapeutic options, asymptomatic or minimally affected patients with CLL are often offered observation outside the context of a clinical trial. Therapy often begins when patients develop profound cytopenias, or when symptoms, such as enlarging bulky lymphadenopathy or debilitating symptoms, substantially impact their quality of life. […] The U.S. Food and Drug Administration approved the biological agents ibrutinib, acalabrutinib, and venetoclax for first-line use in newly diagnosed patients with CLL who require therapy.

• #2 Chronic lymphocytic leukemia treatment algorithm 2022 | Blood Cancer Journal

  https://www.nature.com/articles/s41408-022-00756-9

  The treatment landscape for patients with chronic lymphocytic leukemia (CLL) has changed considerably with the introduction of very effective oral targeted therapies (such as Bruton tyrosine kinase inhibitors and venetoclax) and next-generation anti-CD20 monoclonal antibodies (such as obinutuzumab). These agents lead to improved outcomes in patients with CLL, even among those with high-risk features, such as del17p13 or TP53 mutation and unmutated immunoglobulin heavy chain (IGHV) genes. […] Selecting the right treatment for the right patient requires consideration of disease characteristics and prior treatment sequence, as well as patient preferences and comorbidities. […] The CLL-International Prognostic Index (CLL-IPI) remains the best-validated tool in predicting the time to first therapy among previously untreated patients, which guides selection for early intervention efforts.

• #2 Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

  https://www.mdpi.com/1999-4923/16/1/55

  Targeted therapies and alternative approaches are often considered for patients with TP53mut due to chemotherapy resistance, while patients with mutated immunoglobulins may have a more favorable response to less aggressive treatment strategies. […] The individualized approach to treatment based on these molecular characteristics helps optimize outcomes for patients with CLL. […] CIT remains a viable choice for fit patients with low- and intermediate-risk CLL. […] The combination of FCR stands out as a well-established standard of care for patients eligible for treatment without the presence of del(17p) and/or TP53mut. […] However, it should be noted that CIT has a limited, if any, role in treating CLL because this class of drugs is inferior to BTKi and venetoclax-based regimens in different clinical settings.

• #2 Current and future treatment strategies in chronic lymphocytic leukemia | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-021-01054-w

  In addition to monotherapy with these oral targeted agents, combinations with other types of therapies are also common. […] Less-favorable CLL prognostic markers such as del(17p) or TP53 dysfunction do not lead to long-term remissions with standard chemoimmunotherapy and patients with these disease features are best treated with novel agents. […] BTK inhibitors have become a recommended first-line treatment option in patients with CLL, whether or not they have TP53 dysfunction, and whether or not their disease has relapsed or become refractory on other treatments. […] Patients who were considered high-risk because of del(17p), del(11q), unmutated IGHV, or TP53 dysfunction when chemotherapy was the only available first-line therapy, have much-improved outcomes with BTK-inhibitor therapy.

• #2 Chronic Lymphocytic Leukemia (CLL) Treatment Protocols: Treatment Protocols

  https://emedicine.medscape.com/article/2005390-overview

  Ibrutinib is an oral inhibitor of Bruton’s tyrosine kinase that is indicated for CLL in patients who are treatment-naive or have been previously treated. […] The PI3K inhibitors idelalisib and duvelisib are approved for treatment of relapsed CLL, but have high rates of adverse effects (ie, infections and autoimmune complications). […] Lenalidomide, with or without rituximab, is recommended for refractory or relapsed CLL. […] Treatment options include any of the following: Ibrutinib 420 mg once daily until disease progression; BR regimen; Chlorambucil with or without prednisone; Reduced-dose FCR; Alemtuzumab. […] Treatment recommendations for patients with del (17p) include Acalabrutinib with or without obinutuzumab, Venetoclax with obinutuzumab, and Zanubrutinib. […] The presence of any of the following indications in patients with localized SLL or advanced disease with del (17p) should lead to treatment with chemotherapy or chemoimmunotherapy.

• #2 Current and future treatment strategies in chronic lymphocytic leukemia | Journal of Hematology & Oncology | Full Text

  https://jhoonline.biomedcentral.com/articles/10.1186/s13045-021-01054-w

  Ibrutinib was the first BTK inhibitor investigated for the treatment of patients with CLL. […] The efficacy of ibrutinib compared with chemoimmunotherapy has been established in randomized controlled trials in various settings. […] While ibrutinib is generally well-tolerated, treatment discontinuations or interruptions due to toxicity may limit the efficacy of ibrutinib in patients receiving continuous oral therapy. […] Acalabrutinib is a second-generation BTK inhibitor with reduced off-target activity and improved in vitro selectivity compared with ibrutinib. […] Venetoclax was the first, and remains the only, approved BCL-2 inhibitor for the treatment of patients with relapsed high-risk CLL. […] Approval was based on the results of the pivotal phase 2 study, which was conducted in patients with del(17p) CLL.

• #2 Chronic Lymphocytic Leukemia Treatment (PDQ®) – PDQ Cancer Information Summaries – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK66035/

  In summary, these trials establish the use of venetoclax with obinutuzumab or rituximab, or the use of ibrutinib, acalabrutinib, or zanubrutinib as first-line therapy in patients with previously untreated CLL. A lower rate of atrial fibrillation occurs with acalabrutinib or zanubrutinib than with ibrutinib. […] Unlike ibrutinib or acalabrutinib, which are given continuously until relapse, venetoclax may be stopped after 12 months, with durable maintenance of remission.

• #2 Chronic Lymphocytic Leukemia: Causes, Symptoms, Treatment

  https://www.webmd.com/cancer/lymphoma/chronic-lymphocytic-leukemia-rare

  These are drugs that kill or control cancer cells. Doctors often combine two or more drugs that work in different ways. You may get chemo by pill, shot, or IV. The drugs travel through your blood to reach and affect cells that are dividing too quickly all over your body. This includes certain healthy cells as well as cancer cells. […] These drugs help your body’s immune system find and destroy cancer cells. A type of immunotherapy called monoclonal antibodies is often used to treat CLL. They attach to certain proteins found on cancer cells and stimulate the immune system to destroy these cells. You get them through an IV or as a shot. Your doctor may give you this treatment on its own, but most people get it along with chemo. […] These drugs block certain proteins in and on cancer cells that help them survive and spread. They target proteins found in your CLL cells and spare healthy cells. These drugs are taken as pills.

• #2 Chronic Lymphocytic Leukemia (CLL) Treatment & Management: Approach Considerations, Biologic Regimens and Chemotherapy, Transplantation

  https://emedicine.medscape.com/article/199313-treatment

  A variety of treatment regimens are used in CLL. Although combination chemotherapy regimens including the nucleoside analogue fludarabine were once the most commonly used first-line therapies, non-chemotherapy regimens are currently preferred in the majority of cases. Recommended biologic agents for first-line therapy include the Bruton tyrosine kinase (BTK) inhibitors, a B-cell lymphoma inhibitor (venetoclax), and monoclonal antibodies. Allogeneic stem cell transplantation is the only known curative therapy. […] Treatment selection takes into account the molecular and genetic characteristics of the disease and may comprise monotherapy or combination therapy. Different regimens are recommended for those with a del(17p) or tp53 mutation versus those without those mutations. […] Fludarabine, cyclophosphamide, and rituximab (FCR) remains a recommended first-line treatment only for fit young patients with IGVH hypermutation, as long-term remissions have been reported in this setting.

• #2 What are the Treatments for CLL? – HealthTree for Chronic Lymphocytic Leukemia

  https://healthtree.org/cll/community/what-are-the-treatments-for-cll

  Chronic lymphocytic leukemia (CLL) is no longer treated with chemotherapy. As of the mid-2000s, modern targeted therapies have become the new standard for managing the disease. […] CLL treatment starts when the disease starts causing problems, not only at the time of diagnosis. […] If you find that its nearing the time to start treatment, the list below outlines the top-recommended options by CLL specialists. […] Venetoclax (Venclexta, AbbVie): A BCL-2 inhibitor taken as a daily pill over the course of 1 year and then stopped for first-time therapy. […] Venetoclax is FDA-approved with obinutuzumab as a first-time CLL treatment. […] BTK inhibitors started with ibrutinib (Imbruvica, Janssen Biotech) and have improved to newer versions called acalabrutinib (Calquence, AstraZeneca) and zanubrutinib (Brukinsa, BeiGene).

• #2 Chronic Lymphocytic Leukemia Treatment (PDQ®) – PDQ Cancer Information Summaries – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK66035/

  In patients with poor prognostic factors (especially those with del(17p) or TP53 pathogenic variants), ibrutinib, acalabrutinib, or venetoclax should be considered. […] The following regimens are considered first-line treatment approaches for patients with CLL who are experiencing symptomatic progression: Bruton tyrosine kinase (BTK) inhibitors (acalabrutinib, zanubrutinib, or ibrutinib), Venetoclax with initial use of obinutuzumab or rituximab, Bendamustine and rituximab (BR), Fludarabine, cyclophosphamide, and rituximab (FCR), BTK inhibitor (ibrutinib or acalabrutinib) plus venetoclax, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) (only if Richter syndrome with histological progression is suspected clinically). […] Several large prospective clinical trials have compared these approaches. A chemotherapy-free approach for first-line therapy is usually preferred for most patients, but it is mandatory for patients with del(17p) or TP53-altered disease.

• #2 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  In the relapsed setting, venetoclax showed similar efficacy and safety even after previous therapy with ibrutinib or idelalisib. […] The same regimens considered for first-line therapy for patients with CLL can be readministered in a sequential fashion. […] Autologous T cells can be modified by viral vectors to incorporate antigen receptor specificity for the B-cell antigen CD19 and then infused into previously treated patients. […] Lenalidomide is an oral immunomodulatory agent with response rates of more than 50%, with or without rituximab, for patients with previously treated and untreated disease. […] In a prospective randomized trial, 241 previously untreated patients younger than 66 years with advanced-stage disease received induction therapy with a CHOP-based regimen followed by fludarabine.

• #2 Chronic Lymphocytic Leukemia Treatment (PDQ®) – PDQ Cancer Information Summaries – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK66035/

  Treatment of patients with CLL ranges from observation with treatment of infectious, hemorrhagic, or immunological complications to a variety of therapeutic options administered as single agents or combination therapy. In asymptomatic patients, treatment may be deferred until the disease progresses and symptoms occur. […] A meta-analysis of randomized trials showed no survival benefit for immediate versus delayed therapy for patients with early-stage disease. […] For patients with progressing CLL, treatment will not be curative in most cases. Selected patients treated with allogeneic stem cell transplant have achieved prolonged disease-free survival (DFS), sometimes exceeding 20 years. […] The following clinical factors may be helpful in predicting progression of disease: IGH pathogenic variant, chromosomal abnormalities found by FISH or cytogenetic analysis, beta-2-microglobulin, lymphocyte doubling time.

• #2 Chronic Lymphocytic Leukemia (CLL) Treatment & Management: Approach Considerations, Biologic Regimens and Chemotherapy, Transplantation

  https://emedicine.medscape.com/article/199313-treatment

  Allogeneic stem cell transplantation is the only known curative therapy for CLL. […] Autoimmune manifestations in CLL are myriad, as follows: Positive direct antiglobulin test (DAT; Coombs test) without autoimmune hemolytic anemia (AIHA), AIHA, Immune thrombocytopenia (ITP), Pure red cell aplasia, Autoimmune neutropenia, Cold agglutinin disease, Paraneoplastic pemphigus, Neuropathies, Evans syndrome. […] Refractory splenomegaly and pancytopenia are not uncommon in patients with advanced CLL. Occasionally, these patients require splenectomy.

• #2 Chronic Lymphocytic Leukemia Treatment (PDQ®) – NCI

  https://www.cancer.gov/types/leukemia/hp/cll-treatment-pdq

  Ofatumumab is a humanized anti-CD20 monoclonal antibody. […] Relatively low doses of radiation therapy can be administered for lymphadenopathy that causes problems due to size or encroachment on adjacent organs. […] Alemtuzumab is no longer available commercially in the United States for neoplastic indications but can be obtained from the pharmaceutical company on a compassionate-use basis.

• #2 Treatment for chronic lymphocytic leukaemia (CLL) | Cancer Research UK

  https://www.cancerresearchuk.org/about-cancer/chronic-lymphocytic-leukaemia-cll/treatment

  You may not need treatment straight away if you have early stage CLL and you don’t have symptoms. […] The main treatment for CLL is targeted cancer drugs. […] The main treatments for chronic lymphocytic leukaemia are targeted cancer drugs. You might have a combination of a targeted cancer drug with other anti cancer treatments. […] You might not need treatment straight away, or never need it. Doctors monitor you with regular check ups and tests. They call this 'watch and wait’, 'active monitoring’, or 'active surveillance’. […] When CLL comes back it is called a relapse. You might need more treatment. […] Treatment for CLL can be as tablets or as an injection into a vein as a drip (intravenously). […] Supportive treatments can help to either prevent or control these problems. […] A stem cell transplant isn’t a common treatment for CLL. You usually have stem cells from another person (a donor). […] Rarely, your doctor might suggest an operation to remove your spleen if you have chronic lymphocytic leukaemia. […] How often you have check ups will depend on whether you are having treatment or not and how you are feeling.

• #2 Key Advances in Targeted Therapy for Chronic Lymphocytic Leukemia: Q+A with Nicole Lamanna, MD | Herbert Irving Comprehensive Cancer Center (HICCC) – New York

  https://www.cancer.columbia.edu/news/key-advances-targeted-therapy-chronic-lymphocytic-leukemia-q-nicole-lamanna-md

  Another key clinical trial, the Phase 1/2 BRUIN study is exploring the safety and efficacy of a noncovalent BTK inhibitor called pirtobrutinib, which has demonstrated activity in patients who have previously relapsed after either covalent BTK inhibitors or venetoclax-based therapy. […] There are several other time-limited approaches being evaluated currently, such as all-oral combinations of drugs such as BTK inhibitors and venetoclax. […] There are also new therapies being evaluated for patients with multiply relapsed, refractory disease that look promising for example, noncovalent BTK inhibitors, ROR1 inhibitors, bispecific monoclonal antibodies, and BTK degraders.

• #2 Chronic Lymphocytic Leukemia (CLL) Treatment Protocols: Treatment Protocols

  https://emedicine.medscape.com/article/2005390-overview

  Progressive disease is defined as follows: Increase in lymph nodes by 50% or more; Increase in liver and spleen sizes by 50% or more; Any constitutional symptoms; Any leukocyte count; Circulating B lymphocytes increased by 50% or more; Platelet counts decreased by 50% or more from baseline; Hemoglobin level decreased by more than 2 g/dL from baseline; Bone marrow lymphocytes increased 30% above normal. […] Stable disease is defined as follows: Lymph nodes change from -49% to +49%; Liver and spleen sizes change from -49% to +49%; Any constitutional symptoms; Any leukocyte count; Circulating B lymphocyte counts change from -49% to +49%; Platelet counts change from -49% to +49%; Hemoglobin level increased to 11.0 g/dL or 50% from baseline, or decreased 2 g/dL; No change in bone marrow infiltrate.

• #2 Chronic Lymphocytic Leukemia Treatment

  https://mydoctor.kaiserpermanente.org/mas/structured-content/Treatment_Chronic_Lymphocytic_Leukemia_Treatments_-_Oncology.xml?co=/regions/mas

  Rituximab (Rituxan) is an antibody that attacks leukemia cells. It’s often prescribed on its own or is combined with a traditional chemotherapy drug. […] Idelalisib may have a few of the listed side effects while taking this drug. Inactive infections (like hepatitis) might become active again. […] Venetoclax may be taken alone or with immunotherapy. Side effects might occur, such as reduced healthy blood counts. More serious side effects include pneumonia, infections, and kidney damage (tumor lysis syndrome). […] Chemotherapy is commonly used to kill CLL cells. Chemotherapy drugs can be delivered through a vein or in pill form. […] Chemotherapy drugs enter the bloodstream to attack leukemia cells throughout the body (systemic chemotherapy). […] Chemotherapy may be given along with other treatment (such as an immunotherapy).

• #2 Treatment of Chronic Lymphocytic Leukemia in the Personalized Medicine Era

  https://www.mdpi.com/1999-4923/16/1/55

  Patients ought to be categorized based on the mutational status of the IGHV gene locus, distinguishing between mutated and unmutated variants. […] The understanding of novel agent therapy is advancing with the progression of clinical trial data. […] The emergence of resistance to treatment is related to the progression of subclones with clear proliferative advantages. […] Selecting therapy is a challenging task that requires evaluating the patient regarding all aspects that could interfere, such as other diseases and patient preferences. […] The goal in CLL, as in any cancer, remains to prolong the quality of life and overall survival while offering the least possible toxicity. […] Thanks to new therapeutic targets, the current panorama is moving towards more sustainable, personalized treatments with less risk of toxicity for patients, trying to adapt the therapy to the profile of the patient to whom it is directed.

• #2 Chronic Lymphocytic Leukemia (CLL) > Fact Sheets > Yale Medicine

  https://www.yalemedicine.org/conditions/chronic-lymphocytic-leukemia-cll

  While present-day CLL therapies are already excellent, CLL treatments are improving at such a rapid pace that we have come to expect better-tolerated and more effective therapies every year. Through clinical trials at Yale, many of our CLL patients have access to these next-generation and innovative treatment options.

• #2 CLL / SLL Treatment and Research – CLL Society

  https://cllsociety.org/treatment-and-research/

  CLL / SLL Treatment and Research […] Advancements are happening everyday […] Treatment and research are intimately linked. The best treatments today may be upstaged by new therapies discovered in research in the future. Take your time to learn about treatment options currently available and new ones that are on the way. […] CLL patients are living longer than ever. […] The life expectancy of patients diagnosed with CLL / SLL has improved every decade, largely because of improved care made possible by new treatments and research. […] CLL treatments are better than ever. […] In almost every setting and in almost every subgroup studied, the newer targeted therapies approved since 2015 have proven superior to older protocols using chemotherapy. […] Better single agents and drug combinations show promise.

• #2 What are the Treatments for CLL? – HealthTree for Chronic Lymphocytic Leukemia

  https://healthtree.org/cll/community/what-are-the-treatments-for-cll

  If you have previously taken and become intolerant to venetoclax and a BTK inhibitor, there are other treatment options. […] Pirtobrutinib (Jaypirca, Eli Lilly): A non-covalent BTK inhibitor that binds to the CLL cells in a different way than covalent BTK inhibitors, allowing the medicine to inhibit CLL progression despite prior resistance to covalent BTK inhibitors. […] Liso-cel (Breyanzi, BMS): A CAR T-cell therapy that works by re-engineering your T-cells to more effectively kill CLL cells. […] Allogeneic stem cell transplant: You receive an infusion of donor stem cells (cells capable of forming all other types of blood cells).

• #2 Is Chronic Lymphocytic Leukemia (CLL) Curable?

  https://www.healthline.com/health/cll/cll-cure-are-we-close

  Targeted drugs like idelalisib (Zydelig), ibrutinib (Imbruvica), and venetoclax (Venclexta) go after substances that help cancer cells grow and survive. Even if these drugs cant cure the disease, they may help people live much longer in remission. […] Allogeneic stem cell transplantation is currently the only treatment that offers the possibility of a cure for CLL. […] As of now, no treatment can cure CLL. The closest thing we have to a cure is a stem cell transplant, which carries significant risk and only helps some people survive longer. […] Emerging treatments could change the future for people with CLL. Immunotherapies and other new drugs are already extending survival. In the near future, new combinations of drugs and other types of therapies may help people live longer.

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