Materiały źródłowe

• #1 Waldenstrom Macroglobulinemia: Treatment Options | Lymphoma Research Foundation

  https://www.lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/wm/wmtreatment/

  Although Waldenstrom macroglobulinemia (WM) is an incurable disease, it is treatable, and many patients have a long-term response to treatment. […] For patients who have symptoms, the type and severity of the symptoms (such as age, overall health, and degree of thickness of the blood) help determine the type of treatment selected. […] Once treatment is deemed necessary, the choice of treatment is based on individual patient needs, as well as considerations for short-term and long-term side effects. […] Some patients undergo a procedure called plasmapheresis to temporarily reverse or prevent the symptoms associated with the thickening of the blood. […] In 2015, ibrutinib (Imbruvica) was the first therapy approved by the U.S. Food and Drug Administration (FDA) specifically for patients with Waldenstrm macroglobulinemia.

• #1 Waldenstrom macroglobulinemia | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/waldenstrom-macroglobulinemia

  Treatment options for Waldenstrom macroglobulinemia may include: […] Watchful waiting. If IgM proteins are in the blood, but there are no symptoms, treatment might not be needed right away. Instead, you might have blood tests every few months to monitor your condition. Doctors sometimes call this watchful waiting. There might be no need for treatment for years. […] Plasma exchange. Plasma exchange, also known as plasmapheresis, removes IgM proteins from the blood. It replaces them with healthy blood plasma. Plasma exchange can relieve symptoms caused by having too many IgM proteins in the blood. […] Chemotherapy. Chemotherapy uses strong medicines to kill cancer cells throughout the body. Chemotherapy used alone or with other medicines might be the first treatment for people who have symptoms of Waldenstrom macroglobulinemia. Also, high-dose chemotherapy can stop bone marrow from making cells and may be used to prepare for a bone marrow transplant.

• #1 Waldenstrom Macroglobulinemia Treatment & Management: Approach Considerations, Emergent Treatment, Pharmacologic Therapy

  https://emedicine.medscape.com/article/207097-treatment

  Patients who meet the diagnostic criteria for Waldenstrm macroglobulinemia (WM) on the basis of serum IgM monoclonal protein, bone marrow lymphoplasmacytic infiltration, or both but who do not have evidence of end-organ damage are considered to have indolent disease or smoldering Waldenstrm macroglobulinemia. No treatment is indicated for asymptomatic disease. […] Clinical indications for initiation of therapy include the following: Recurrent fever, night sweats, weight loss, fatigue; Hyperviscosity; Lymphadenopathy, symptomatic or bulky (5 cm in maximum diameter); Symptomatic hepatomegaly and/or splenomegaly; Symptomatic organomegaly and/or organ or tissue infiltration; Peripheral neuropathy from WM. […] For patients with clinical or laboratory indications for treatment, the major classes of effective agents include the following: Monoclonal antibodies (eg, rituximab); Alkylating agents; Purine nucleoside analogs; Proteasome inhibitors; Immunomodulatory drugs; Mechanistic (mammalian) target of rapamycin (mTOR) inhibitors; Brutons tyrosine kinase (BTK) inhibitors.

• #1 Waldenström macroglobulinemia treatment algorithm 2018 | Blood Cancer Journal

  https://www.nature.com/articles/s41408-018-0076-5

  Waldenstrm macroglobulinemia is often an indolent disorder, and many patients are candidates for observation with careful monitoring. […] For symptomatic patients, one must distinguish between those patients whose symptoms are related to immunologic manifestations associated with the IgM monoclonal protein and those that have symptoms related to progressive marrow and nodal infiltration with lymphoplasmacytic lymphoma. […] In Waldenstrm macroglobulinemia, the driver for therapy in the majority of patients is progressive anemia, secondary to bone marrow replacement by lymphoplasmacytic lymphoma. […] An algorithm is provided on the management of asymptomatic individuals and the sequence used for chemotherapeutic intervention of symptomatic patients. […] The therapy of choice is plasma exchange. A single plasma exchange can normalize the viscosity and allow chemotherapy to successfully reduce the tumor mass.

• #1 5 Innovative Waldenstrom’s Macroglobulinemia Treatment Options | MD Anderson Cancer Center

  https://www.mdanderson.org/cancer-types/waldenstroms-macroglobulinemia/waldenstroms-macroglobulinemia-treatment.html

  Immunotherapy: On the cutting edge of new treatments, immunotherapies to treat Waldenstrm’s may include: Monoclonal antibodies, including Rituxan (rituximab), Biological therapies that develop antibodies that destroy tumor cells, Proteasome inhibitors, such as Velcade (bortezomib), Immune modulators, such as thalidomide and lenalidomide, that modify the environment of the tumor cell and allow it to die, Targeted therapies that attack cancer cells by using small molecules to block pathways cells use to survive and multiply. […] Stem cell transplantation: If Waldenstrm’s macroglobulinemia does not respond to chemotherapy or if it returns, a stem cell transplant may be recommended. MD Anderson’s stem cell transplantation program is among the most active and advanced in the nation. […] Plasma exchange: If you develop symptoms because your blood is too thick, plasma can be removed and replaced with normal plasma from a healthy donor. This quickly relieves the symptoms until chemotherapy or immunotherapy can destroy the Waldenstrm’s cells that are causing the buildup of abnormal protein. […] Watchful waiting: Your doctor carefully monitors the disease and your symptoms, suggesting treatment if needed.

• #1 Waldenstrom Macroglobulinemia Treatment & Management: Approach Considerations, Emergent Treatment, Pharmacologic Therapy

  https://emedicine.medscape.com/article/207097-treatment

  In addition, clinical trials are currently exploring the following for treatment of WM: Proteasome inhibitors – Ixazomib, dexamethasone, and rituximab; BTK inhibitors – Tirabrutinib; second generation, non-covalent BTK inhibitors (eg, vecabrutinib, LOXO-305) are being investigated for use in WM refractory to ibrutinib; The anti-CD38 monoclonal antibody daratumumab. […] The treatment of choice for symptoms related to hyperviscosity is urgent plasmapheresis. […] Chemotherapy should be considered soon after stabilization to reduce the production of the paraprotein by the malignant lymphocytes. […] Front-line therapy for Waldenstrm macroglobulinemia (WM) consists of monoclonal antibody, alkylating agents, nucleoside analogues, and combination therapy. […] Rituximab, an anti-CD20 monoclonal antibody, produces response rates of 20-50% irrespective of prior exposure to chemotherapy.

• #1 When to Treat People with Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/treating/people-with-wm.html

  The drugs used to treat WM can be given in a variety of combinations and schedules depending on the situation. […] In general, rituximab is not usually given when the IgM level is very high because it can make the IgM level temporarily go up even higher. Plasmapheresis may be used first to lower the IgM level before starting rituximab. Another option is to give rituximab along with ibrutinib because the combination can rapidly reduce the level of IgM. […] If a stem cell transplant might be used later on, many experts recommend not giving certain chemo drugs (chlorambucil, bendamustine, cladribine, or fludarabine) because they might affect the blood stem cells in the bone marrow. […] Here are some of the drugs and combinations that might be used as the first treatment for WM. […] During treatment, youll have regular visits with your doctor, who will ask you about your symptoms, do physical exams, and test your blood to see how well the treatment is working.

• #1 Waldenstrom macroglobulinemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/non-hodgkin-lymphoma/treatment/treatment-by-type/waldenstrom-macroglobulinemia

  A single targeted therapy drug or a combination of drugs may be used. Targeted therapy may be used alone or with chemotherapy. […] Targeted therapy drugs used to treat Waldenstrom macroglobulinemia include: rituximab (Rituxan and biosimilars), ibrutinib (Imbruvica), acalabrutinib (Calquence), zanubrutinib (Brukinsa), bortezomib (Velcade), lenalidomide (Revlimid). […] Chemotherapy uses drugs to destroy cancer cells. The drugs that may be used for Waldenstrom macroglobulinemia include: bendamustine (Treanda, Benvyon, Esamuze), fludarabine (Fludara), cyclophosphamide (Procytox), chlorambucil (Leukeran), cladribine. […] Targeted therapy drugs or immunotherapy drugs may be used along with chemotherapy drugs. Corticosteroids, such as dexamethasone or prednisone, may also be given. […] A stem cell transplant replaces stem cells. If you are healthy enough, you may be offered a stem cell transplant for Waldenstrom macroglobulinemia that comes back (relapses) after treatment or doesn’t respond to other treatments (called refractory disease). […] Talk to your doctor about clinical trials open to people with NHL in Canada. Clinical trials look at new ways to prevent, find and treat cancer.

• #1 Efficacy and safety of front-line treatment regimens for Waldenstrom macroglobulinaemia: a systematic review and meta-analysis | Blood Cancer Journal

  https://www.nature.com/articles/s41408-023-00916-5

  Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. […] In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. […] Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted. […] Major classes of agents commonly used for the treatment of WM include monoclonal antibodies, alkylating agents, proteasome inhibitors, and Bruton Tyrosine Kinase inhibitors (BTKi). […] The BTKi ibrutinib was shown to be an effective therapy for newly diagnosed WM and is approved by the Food and Drug Administration for this indication.

• #1 Waldenstrom Macroglobulinemia: Tailoring Therapy for the Individual

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9362871/

  The combination of rituximab cyclophosphamide and dexamethasone was introduced in 2007 and produced an overall response rate of 83%; PR in 74%. […] Bortezomib, rituximab, and dexamethasone was found to be highly effective in the treatment of macroglobulinemia. […] Carfilzomib is active in the treatment of macroglobulinemia without producing neuropathy. […] Ixazomib as a non-neurotoxic orally administered proteasome inhibitor offers obvious advantages in an elderly population. […] In a phase II trial, bendamustine with and without rituximab resulted in an overall response rate of 83.3% and a PFS of 13.2 months in relapsed refractory disease. […] Acalabrutinib is approved for the treatment of chronic lymphatic leukemia and mantle cell lymphoma. […] The abrupt withdrawal of ibrutinib because of toxicity or surgery can result in a rapid rise in the IgM level, flare, associated with an exacerbation in symptoms of macroglobulinemia. […] Although there is no single best initial therapy for patients with macroglobulinemia, ibrutinib is essential for those patients who have central nervous system involvement, the so-called Bing-Neel syndrome. […] The decision process for relapsed refractory disease is more complex.

• #1 Treatment paradigm in Waldenström macroglobulinemia: frontline therapy and beyond

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9058343/

  Another common chemoimmunotherapy regimen utilized in the treatment of WM is dexamethasonerituximabcyclophosphamide (DRC). A phase 2 study of 72 patients with previously untreated WM was treated with DRC regimen that consisted of six 21-day courses of dexamethasone intravenous (IV) 20mg and rituximab IV 375mg/m2 on day 1 and oral cyclophosphamide 100mg/m2 twice daily (days 15). […] Various PIs, including bortezomib, ixazomib, and carfilzomib have been evaluated in WM and have demonstrated good clinical efficacy. […] Ibrutinib was the first BTK inhibitor that received approval from the Food and Drug Administration (FDA) in 2015 for treatment of patients with WM based on a study demonstrating excellent efficacy in patients with relapsed/refractory WM. […] Acalabrutinib, another BTK inhibitor, has also demonstrated efficacy in RRWM.

• #1 A Canadian Perspective on the Treatment of Waldenström Macroglobulinemia

  https://www.mdpi.com/1718-7729/29/10/560

  Chemotherapy combined with the anti-CD20 monoclonal antibody rituximab is widely used to treat WM. The only CIT to be evaluated in a phase 3 randomized controlled trial for the first-line treatment of WM is bendamustine-rituximab (BR). […] Other cyclophosphamide-based therapies including cyclophosphamide and rituximab combined with prednisone (R-CP), vincristine and prednisone (R-CVP), or vincristine, doxorubicin, and prednisone (R-CHOP) have demonstrated efficacy in WM, with ORRs of approximately 90–95% being achieved in clinical studies. […] Rituximab monotherapy has also been studied in WM, with clinical trials reporting ORRs at or below 50% and median PFS under 24 months. […] The benefit of rituximab maintenance following response to BR is unclear given that the StiL NHL7-2008 trial did not demonstrate a survival benefit for maintenance rituximab compared with observation in patients with WM.

• #1 Waldenstrom macroglobulinemia | UM Health-Sparrow

  https://www.uofmhealthsparrow.org/departments-conditions/conditions/waldenstrom-macroglobulinemia

  Targeted therapy. Targeted therapy uses medicines that attack specific chemicals in the cancer cells. By blocking these chemicals, targeted treatments can cause cancer cells to die. Targeted therapy medicines might be used with other treatments, such as chemotherapy or immunotherapy. […] Immunotherapy. Immunotherapy is a treatment with medicine that helps your body’s immune system to kill cancer cells. Your immune system fights off diseases by attacking germs and other cells that shouldn’t be in your body. Cancer cells survive by hiding from the immune system. Immunotherapy helps the immune system cells find and kill the cancer cells. […] Bone marrow transplant. In select instances, a bone marrow transplant, also known as a stem cell transplant, may be a treatment for Waldenstrom macroglobulinemia. During this procedure, high doses of chemotherapy wipe out the bone marrow. Healthy blood stem cells go into the body to rebuild healthy bone marrow. […] Supportive care. Supportive care, which is also called palliative care, focuses on relieving pain and other symptoms of serious illness. This extra layer of care can support you as you undergo other treatments, such as chemotherapy.

• #1 Waldenstrom Macroglobulinemia Treatment & Management: Approach Considerations, Emergent Treatment, Pharmacologic Therapy

  https://emedicine.medscape.com/article/207097-treatment

  In 2015, ibrutinib (Imbruvica) became the first drug approved by the US Food and Drug Administration (FDA) for treatment of WM. […] In 2018, the FDA approved an expanded indication for ibrutinib in WM beyond its use as a monotherapy to include combination use with rituximab. […] Zanubrutinib (Brukinsa) became the second BTK inhibitor approved for Waldenstrm macroglobulinemia. […] The purine nucleoside analogues fludarabine and cladribine have demonstrated activity against Waldenstrm macroglobulinemia. […] Combination chemotherapy approaches have been explored, with response rates of more than 75%. […] Salvage therapy for patients with resistant disease or relapse includes the reuse or alternative use of front-line agent, combination therapy, thalidomide (with or without steroids), bortezomib, everolimus, alemtuzumab, and stem cell transplantation. […] High-dose chemotherapy with autologous peripheral blood cell transplantation is reserved for selected younger patients with primary refractory or relapsed disease.

• #1 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  Acalabrutinib is a potent targeted BTK antagonist that, in contrast to ibrutinib, has little effect on estimated glomerular filtration rate, Tec, and Src family kinases, or interleukin 2–inducible T-cell kinase signalling. Acalabrutinib has been investigated in a multicentre, single-arm study of treatment-naïve and relapsed-refractory patients. With a median follow-up of 27.4 months, 13 of 14 treatment-naïve patients and 86 of 92 relapsed or refractory patients achieved an overall response. Grade 3–4 atrial fibrillation occurred in one (1%) patient and grade 3–4 bleeding occurred in three (3%) patients. The most common serious adverse events were lower respiratory tract infection (n=7;7%), pneumonia (n=7;7%). Acalabrutinib does not currently have marketing approval for treatment of WM in Europe or the UK.

• #1 Waldenstrom Macroglobulinemia: Treatment Options | Lymphoma Research Foundation

  https://www.lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/wm/wmtreatment/

  There are many other drugs that can be used to manage this disease, alone and/or in various combinations, including the following: Bendamustine (Treanda), Cladribine (Leustatin), Bortezomib (Velcade), Carfilzomib (Kyprolis), Chlroambucil (Leukeran), CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), CVP (cyclophosphamide, vincristine, prednisone), Cyclophosophamide (Cytoxin), Fludarabine (Fludara), Ibrutinib (Imbruvica) + Rituximab (Rituxan), Ixazomib (Ninlaro), Rituximab (Rituxan) Other agents used alone or in combination for primary treatment are cyclophosphamide (Cytoxan), carfilzomib (Kyprolis), and thalidomide (Thalomid), Zanubrutinib (Brukinsa). […] Several promising new drugs and drug combinations are being studied in clinical trials for the treatment of patients with Waldenstrm macroglobulinemia (some for relapsed/refractory disease), including: 19(T2)28z1XX (Chimeric antigen receptor [CAR] T cell therapy targeting CD19), Acalabrutinib (Calquence), Daratumumab (Darazalex), Tirabrutinib (Velexbru), Ulocuplumab, Venetoclax (Brukinsa). […] Chimeric antigen receptor-modified T-cell therapy targeting CD19 is another promising therapy for patients with Waldenstrm macroglobulinemia.

• #1 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  BTK-Is should be continued until there is disease progression or unacceptable toxicity. Mechanisms of resistance are best characterised in patients receiving ibrutinib for treatment of chronic lymphocytic leukaemia and involve cysteine-to-serine mutation in BTK and mutations in PLCγ2, which lies downstream of BTK. Patients should be monitored for IgM flare and plans should be put in place for subsequent treatment following BTK discontinuation. Covalent BTK-antagonists should be avoided following the development of resistance to ibrutinib or zanubrutinib, owing to the risk of mutations on the BTK and PLGC2 that predict for cross resistance. However, non-covalent BTK antagonists may be effective. […] The BCL-2 antagonist venetoclax effectively induces apoptosis of LPL cells in vitro and has been shown to be effective in the treatment of patients with relapsed/refractory WM. In a phase 2 study of 32 patients (all MYD88 L2625P, 16 post BTK-inhibitor), the overall, major, and VGP response rates were 84%, 81%, and 19%, respectively. The major response rate was lower in those with refractory versus relapsed disease (50% vs. 95%; P=0.007). The median progression-free survival was 30 months. CXCR4 mutations did not affect treatment response or progression-free survival. Alternative BCL-2 antagonists are being investigated in mature B-cell lymphomas, including WM.

• #1 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  Pirtobrutinib is a non-covalent BTK-I, which inhibits both wildtype and C481-mutant BTK. It leads to continuous BTK inhibition throughout the dosing interval and has been demonstrated to overcome BTK-resistance. The BRUIN phase 1/2 study across patients with B-cell malignancies reported striking activity in a cohort of heavily pre-treated patients with WM. Of the 78 WM patients, (median prior therapies = 3, of which 61 (78%) had received ≥1 prior BTKi (≥2 BTKi in 13/61 patients, 21%). The major response rate for the 72 response-evaluable patients was 68% (95% CI, 56-79), including 17 VGPRs (24%) and 32 PRs (44%). In the safety cohort of all pirtobrutinib-treated patients with B-cell malignancies (n=725), the most frequent grade ≥3 treatment emergent adverse event was neutropenia (20%, n=143). Low rates of grade ≥3 adverse events of hypertension (3%, n=20), haemorrhage (2%, n=16), and atrial fibrillation/flutter (1%, n=7) were observed. Overall, 15 (2%) patients discontinued treatment owing to a treatment-related adverse events. Pirtobrutinib is not currently licensed for the treatment of WM in Europe or the UK.

• #1 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  CAR-T cell therapy (MB-106) has been granted orphan drug status by the US Food and Drug Administration and is showing promising results in early phase trials. In a single-centre study for patients with RR indolent B-cell lymphoma, six patients with WM received the third-generation, fully human CD20 targeting CAR-T product (MB-106) and four patients underwent response assessment. This was a heavily pre-treated cohort (median 6.5 prior lines, all 4 patients were BTK-I refractory). Toxicity was manageable; no patients experienced grade 3 cytokine release syndrome and there was no immune effector cell-associated neurotoxicity. All patients responded to treatment: 2 achieved CR, 1 PR and 1 MR. Durability of response is awaited. […] Autologous stem cell transplantation is an option in selected chemo-sensitive patients at second line. In patients for whom this may be an option, drugs that impair stem cell mobilisation (fludarabine and chlorambucil) should be avoided. Allogeneic transplantation is an appropriate option in highly selected patients who are refractory to chemo-immunotherapy and BTK-Is.

• #1 Treatment Regimens and Considerations – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/treatment-regimens-and-considerations-1/

  There are many different treatment options available to people with Waldenstrom macroglobulinemia (WM). If you’re having WM-related symptoms that require treatment, your hematologist/oncologist will recommend a treatment plan tailored to your specific medical situation. […] There are a number of recommended therapy regimens that are appropriate choices for treating WM. Your hematologist/oncologist will take several factors into account when deciding what regimen is best for you, including: Your age, Your general health and quality of life, The type and extent of your symptoms, Blood, bone marrow, and other test results, The need for rapid disease control, Any previous treatments you’ve had to manage your WM, Your eligibility and possible need for a stem cell transplant now or in the future.

• #1 Waldenstrom Macroglobulinemia Treatment & Management: Approach Considerations, Emergent Treatment, Pharmacologic Therapy

  https://emedicine.medscape.com/article/207097-treatment

  Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) guidelines recommend a single cycle of rituximab (with no maintenance therapy) for patients with any of the following: Hemoglobin 11 g/dL or symptomatic; Platelet count 120 x 109/L; IgM-related neuropathy; WM-associated hemolytic anemia; Symptomatic cryoglobulinemia. […] For patients with bulky disease, profound cytopenia (hemoglobin 10 g/dL, platelets 100 x 109/L), constitutional symptoms, or hyperviscosity symptoms, mSMART guidelines recommend four to six cycles of bendamustine plus rituximab, preceded by plasmapheresis in patients with symptomatic hyperviscosity. […] For relapsed disease, patients who tolerated initial treatment well and achieved a durable response (3 years or longer) with it can be retreated with the original regimen.

• #1 Waldenstrom Macroglobulinemia Treatment & Management: Approach Considerations, Emergent Treatment, Pharmacologic Therapy

  https://emedicine.medscape.com/article/207097-treatment

  The US Food and Drug Administration (FDA) has approved an expanded indication for ibrutinib in WM beyond its use as a monotherapy to include combination use with rituximab. […] Autologous stem cell transplantation should be considered at the first or second relapse in select patients with chemosensitive disease, especially if the first remission duration is short ( 2 years). […] Treatment recommendations from the 10th International Workshop on Waldenstrm Macroglobulinemia are as follows: Alkylating drugs (bendamustine, cyclophosphamide) and proteasome inhibitors (bortezomib, carfilzomib, ixazomib), both in combination with rituximab, as well as BTK inhibitors (ibrutinib, zanubrutinib), alone or in combination with rituximab, are preferred first-line therapy options for symptomatic patients.

• #1 Treatment Regimens and Considerations – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/treatment-regimens-and-considerations-1/

  The choice of treatment after relapse depends on several things, including: The initial treatment used, Your tolerance of the initial treatment, The duration of response, meaning how soon did the cancer return after treatment?, Your eligibility for a stem cell transplant. […] Fortunately, there are many treatment choices for people who relapse and the options are continually increasing. You might also consider participating in a clinical trial. When weighing treatment options following relapse, it’s perfectly appropriate to get a second opinion from a WM expert.

• #1 Treatment landscape for R/R Waldenstrom’s macroglobulinemia

  https://lymphomahub.com/medical-information/treatment-landscape-for-rr-wm

  Acalabrutinib has been proven as an effective BTKi in R/R WM. […] BCL2 inhibitors, such as venetoclax, are emerging options for R/R WM. […] Given the impact of CXCR4 mutational status on clinical outcomes for BTKis in WM, phase I and II trials are currently investigating CXCR4-targeted agents. […] It is recommended that treatment should be initiated in symptomatic cases of WM. […] For patients with early relapse (612 months) after first-line rituximab-chemotherapy, BTKis are the preferred regimen and bortezomib is an alternative option. […] Although there are many treatment options available for R/R WM, including immunochemotherapies, BTKis, and PIs there is no consensus treatment approach given the paucity of randomized clinical trials.

• #1 Understanding the Treatment of Waldenström’s Macroglobulinemia – The ASCO Post

  https://ascopost.com/issues/september-25-2023/understanding-the-treatment-of-waldenstroem-s-macroglobulinemia/

  Dr. Nooka concluded by summarizing his preferred options for treatment in various settings: Newly Diagnosed Disease: Bendamustine/rituximab, ibrutinib/rituximab, or zanubrutinib; First Relapse: For relapse on a covalent BTK inhibitor (ibrutinib, zanubrutinib, acalabrutinib, orelabrutinib, tirabrutinib) bendamustine/rituximab; for relapse off therapy, after bendamustine/rituximab or other chemoimmunotherapy, or in a covalent BTK inhibitor naive patient bendamustine/rituximab, ibrutinib/rituximab, zanubrutinib; Salvage Therapy: Venetoclax, pirtobrutinib, proteasome inhibitor combinations, autologous stem cell transplantation in select patients, or repeat previously used fixed-duration therapy.

• #1 Lymphoplasmacytic lymphoma and Waldenström’s macroglobulinaemia | Lymphoma Action

  https://lymphoma-action.org.uk/types-lymphoma-non-hodgkin-lymphoma/lymphoplasmacytic-lymphoma-and-waldenstroms-macroglobulinaemia

  Treatment is given in cycles over a period of a few months. In each cycle, you receive treatment some weeks but not others. The rest periods between treatments allow your body to recover before the next treatment. […] As well as treatment for the lymphoma itself, you might need treatment for symptoms of WM or side effects of treatments. This is sometimes called supportive care because these treatments don’t treat the lymphoma but support your body through your lymphoma treatment. […] If your blood becomes too thick because of high levels of IgM, you might need to have it thinned by a procedure called plasmapheresis (plasma exchange). You might have plasmapheresis to keep your symptoms under control, to reduce your IgM levels before starting treatment for WM, or before having a blood transfusion.

• #1 Treating Waldenstrom Macroglobulinemia | American Cancer Society

  https://www.cancer.org/cancer/types/waldenstrom-macroglobulinemia/treating.html

  If treatment is needed for Waldenstrom macroglobulinemia (WM), several types can be used: […] The 2 main ways to treat WM are chemotherapy and different types of biological therapy (immunotherapy). One or both of these types of treatments might be used. […] In recent years, much progress has been made in treating people with WM. A number of newer drugs have been found to work against WM, but few studies have compared them to see which ones are best. Because of this, there is no single standard treatment for all patients. […] It’s important to discuss all treatment options, including their goals and possible side effects, with your doctors to help make the decision that best fits your needs. […] Clinical trials are carefully controlled research studies that are done to get a closer look at promising new treatments or procedures. Clinical trials are one way to get state-of-the-art cancer treatment.

• #1 Efficacy and safety of front-line treatment regimens for Waldenstrom macroglobulinaemia: a systematic review and meta-analysis | Blood Cancer Journal

  https://www.nature.com/articles/s41408-023-00916-5

  In this systematic review, evidence from comparative and non-comparative studies suggests that among the options recommended by the IWWM, bendamustine-based regimens may result in improved response rates and PFS compared to BTKi- and bortezomib-based regimens. […] The advanced age of the typical WM patient, as well as the chronic, incurable nature of the disease, means that quality of life (QOL) and treatment-related toxicities are very important considerations when making treatment decisions. […] The future of WM treatment is however likely to involve a genomically stratified treatment approach. Collaborative, international clinical trials comparing BR against other front-line treatment options in patients stratified by MYD88 and CXCR4 mutational status are called for to definitively identify the optimal first-line treatment for WM.

• #1 How We Treat Waldenström’s Macroglobulinemia | Dana-Farber Cancer Institute

  https://www.dana-farber.org/cancer-care/types/waldenstroms-macroglobulinemia/treatment

  Our scientists are working to understand the genetic basis and pathogenesis of WM and are developing therapies. […] These scientific advances inform clinical trials that lead to the development and adoption of many treatments for WM, including the approval of BTK-inhibitors for WM. […] Some of the new agents being tested in our Center’s clinical trials include covalent (ibrutinib, zanubrutinib, acalabrutinib) and non-covalent (pirtobrutinib) BTK-inhibitors, BTK-degraders, BCL-2 inhibitors (venetoclax), CXCR4 inhibitors (ulocuplumab, mavorixafor) and immune-based therapies that include antibodies conjugated to payloads that kill tumor cells, and bi-specific antibodies that stimulate immune T-cells to kill WM cells. Combination studies using these agents are also being investigated.

• #2 Waldenstrom macroglobulinemia | Canadian Cancer Society

  https://cancer.ca/en/cancer-information/cancer-types/non-hodgkin-lymphoma/treatment/treatment-by-type/waldenstrom-macroglobulinemia

  Waldenstrom macroglobulinemia is an indolent (slow-growing) type of B-cell non-Hodgkin lymphoma (NHL). […] You may be offered the following treatments for Waldenstrom macroglobulinemia. Your healthcare team will suggest treatments based on your needs and work with you to develop a treatment plan. […] If Waldenstrom macroglobulinemia is developing slowly and not causing symptoms, you may be offered watchful waiting. The healthcare team will use tests to closely monitor the lymphoma. When symptoms appear or there are signs that the disease is progressing more quickly, they will offer other treatments. […] Targeted therapy uses drugs to target specific molecules (such as proteins) on cancer cells or inside them. These molecules help send signals that tell cells to grow or divide. By targeting these molecules, the drugs stop the growth and spread of cancer cells while limiting harm to normal cells. Targeted therapy may also be called molecular targeted therapy.

• #2 Waldenström Macroglobulinemia: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17951-waldenstrom-macroglobulinemia

  Waldenstrm macroglobulinemia (WM) is a rare, slow-growing cancer that affects your blood cells. […] Healthcare providers can’t cure this condition, but they do have treatments that can manage symptoms. […] Theres no cure for Waldenstrm macroglobulinemia. But there are treatments that ease and sometimes eliminate symptoms. […] As there isn’t a cure for this condition, the best treatment is one that relieves symptoms with the least amount of side effects. Your healthcare provider will work with you to customize treatment. Options for WM include: […] Plasmapheresis (plasma exchange). Providers use a machine to filter abnormal IgM from your plasma, the liquid part of your blood. They return the plasma to your bloodstream. Providers use this treatment to ease symptoms caused by thickening blood.

• #2 When is Treatment Needed for WM? – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/when-is-treatment-needed-for-wm/

  Active treatment should only begin when a person becomes symptomatic and the disease is causing problems. Treatment should not be started based on blood tests alone. […] Experts consider the following signs and symptoms of WM appropriate reasons for treatment: Anemia (low red blood cell account and low hemoglobin) due to infiltration of the bone marrow with WM cells. […] The following complications may also be an indication for therapy: Hyperviscosity syndrome (excessive thickness of the blood due to high IgM levels).

• #2 Waldenstrom Macroglobulinemia Treatment & Management: Approach Considerations, Emergent Treatment, Pharmacologic Therapy

  https://emedicine.medscape.com/article/207097-treatment

  In addition, clinical trials are currently exploring the following for treatment of WM: Proteasome inhibitors – Ixazomib, dexamethasone, and rituximab; BTK inhibitors – Tirabrutinib; second generation, non-covalent BTK inhibitors (eg, vecabrutinib, LOXO-305) are being investigated for use in WM refractory to ibrutinib; The anti-CD38 monoclonal antibody daratumumab. […] The treatment of choice for symptoms related to hyperviscosity is urgent plasmapheresis. […] Chemotherapy should be considered soon after stabilization to reduce the production of the paraprotein by the malignant lymphocytes. […] Front-line therapy for Waldenstrm macroglobulinemia (WM) consists of monoclonal antibody, alkylating agents, nucleoside analogues, and combination therapy. […] Rituximab, an anti-CD20 monoclonal antibody, produces response rates of 20-50% irrespective of prior exposure to chemotherapy.

• #2 Waldenström Macroglobulinemia: Symptoms, Causes & Treatment

  https://my.clevelandclinic.org/health/diseases/17951-waldenstrom-macroglobulinemia

  Immunotherapy. This treatment uses your body’s immune system to destroy or slow the growth of WM cells. Providers commonly prescribe rituximab (Rituxan) alone or with chemotherapy. […] Chemotherapy. Your providers may prescribe cancer-killing medications alone or in combination with immunotherapy. […] Corticosteroids. You may take a steroid, like dexamethasone, along with immunotherapy and chemo. This treatment fights cancer and reduces the side effects of treatment. […] Targeted therapy. This treatment blocks proteins that cancer cells use to make more copies. Ibrutinib (Imbruvica) and zanubrutinib (Brukinsa) are both targeted therapies approved by the U.S. Food and Drug Administration (FDA) to treat WM. […] Stem cell transplant. Providers replace bone marrow affected by abnormal cells with healthy bone marrow. This is uncommon and used only in select people.

• #2 Waldenstrom Macroglobulinemia Treatment & Management: Approach Considerations, Emergent Treatment, Pharmacologic Therapy

  https://emedicine.medscape.com/article/207097-treatment

  The US Food and Drug Administration (FDA) has approved an expanded indication for ibrutinib in WM beyond its use as a monotherapy to include combination use with rituximab. […] Autologous stem cell transplantation should be considered at the first or second relapse in select patients with chemosensitive disease, especially if the first remission duration is short ( 2 years). […] Treatment recommendations from the 10th International Workshop on Waldenstrm Macroglobulinemia are as follows: Alkylating drugs (bendamustine, cyclophosphamide) and proteasome inhibitors (bortezomib, carfilzomib, ixazomib), both in combination with rituximab, as well as BTK inhibitors (ibrutinib, zanubrutinib), alone or in combination with rituximab, are preferred first-line therapy options for symptomatic patients.

• #2 Waldenström Macroglobulinemia – Hematology & Oncology

  https://www.hematologyandoncology.net/archives/january-2015/waldenstrom-macroglobulinemia/

  Drug combinations such as thalidomide/rituximab, bortezomib (Velcade, Millennium Pharmaceuticals)/rituximab, carfilzomib/rituximab, and bendamustine (Treanda, Teva)/rituximab have shown excellent results. […] One risk of treating patients with rituximab-based regimens is the IgM flare, also called the rituximab flare. […] IgM flare is seen in more than half of the patients treated with rituximab alone, and in up to 30% of patients treated with rituximab-based combination regimens. […] The mTOR inhibitor everolimus has metabolic side effects, resulting in elevations of triglycerides and blood sugar. […] Autologous stem cell transplantation is a viable option in patients at the time of relapse if they retain chemotherapy sensitivity. […] The use of allogeneic stem cell transplantation should be limited to clinical trial settings.

• #2 Waldenstrom Macroglobulinemia: Treatment Options | Lymphoma Research Foundation

  https://www.lymphoma.org/understanding-lymphoma/aboutlymphoma/nhl/wm/wmtreatment/

  There are many other drugs that can be used to manage this disease, alone and/or in various combinations, including the following: Bendamustine (Treanda), Cladribine (Leustatin), Bortezomib (Velcade), Carfilzomib (Kyprolis), Chlroambucil (Leukeran), CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), CVP (cyclophosphamide, vincristine, prednisone), Cyclophosophamide (Cytoxin), Fludarabine (Fludara), Ibrutinib (Imbruvica) + Rituximab (Rituxan), Ixazomib (Ninlaro), Rituximab (Rituxan) Other agents used alone or in combination for primary treatment are cyclophosphamide (Cytoxan), carfilzomib (Kyprolis), and thalidomide (Thalomid), Zanubrutinib (Brukinsa). […] Several promising new drugs and drug combinations are being studied in clinical trials for the treatment of patients with Waldenstrm macroglobulinemia (some for relapsed/refractory disease), including: 19(T2)28z1XX (Chimeric antigen receptor [CAR] T cell therapy targeting CD19), Acalabrutinib (Calquence), Daratumumab (Darazalex), Tirabrutinib (Velexbru), Ulocuplumab, Venetoclax (Brukinsa). […] Chimeric antigen receptor-modified T-cell therapy targeting CD19 is another promising therapy for patients with Waldenstrm macroglobulinemia.

• #2 Treatment paradigm in Waldenström macroglobulinemia: frontline therapy and beyond

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9058343/

  The current commonly used frontline systemic therapy categories can be categorized as chemoimmunotherapy, PI-based therapy, and BTK inhibitor-based therapy. Rituximab is an anti-CD20 monoclonal antibody that demonstrates response rates of 3040% as a single-agent therapy in patients with WM. Treatment with single-agent rituximab has largely been superseded by chemoimmunotherapy regimens that have demonstrated superior responses and outcomes. Chemoimmunotherapy regimens include anti-CD20 monoclonal antibody rituximab as the backbone along with an alkylating agent like bendamustine or cyclophosphamide. […] Bendamustine in combination with rituximab (BR) represents a commonly employed frontline chemoimmunotherapy for WM. […] The BR regimen consists of bendamustine 90mg/m2 days 1 and 2, and rituximab 375mg/m2 on day 1 of each cycle, administered every 28days for total of six cycles.

• #2 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  Autologous stem cell transplantation remains a second-line option for selected patients, achieving at least a partial response. […] Patients considered to be unfit to receive chemo-immunotherapy may be treated with oral chlorambucil or rituximab monotherapy (four to eight doses per month). However, caution must be applied with rituximab (monotherapy or in combination with chemotherapy) owing to the risk of IgM flare, which in 40–50% of cases will induce rapid increases in serum IgM, ranging from 25% to 300%, and could worsen hyperviscosity symptoms. The risk of IgM flare may be mitigated by offering pre-emptive plasmapheresis. The reduced toxicity of monotherapy is also offset by a median time to response of 4 months and a shorter progression-free survival (PFS) of 23.1 months. […] Dexamethasone in combination with rituximab and cyclophosphamide (DRC) (six 28-day cycles) has an objective response rate of 83% and median PFS of 35 months. The combination is safe and generally very well tolerated, with the main toxicities being cytopenias (9% grade 3 neutropenia). Owing to the risk of hyper-IgM syndrome, rituximab is deferred or plasma exchange utilised upfront to ensure that the IgM paraprotein measures <40g/L before rituximab dosing.

• #2 New Advances in Waldenström Macroglobulinemia

  https://www.onclive.com/view/new-advances-in-waldenstr-m-macroglobulinemia

  Over the past decade, Bruton tyrosine kinase (BTK) inhibitors have become a standard treatment option. […] The advantages of BTK inhibitors include the ease of oral administration and the absence of risk of myeloid neoplasms. […] Beyond chemoimmunotherapy and BTK inhibitors, BCL2 antagonists such as venetoclax and noncovalent BTK inhibitors such as pirtobrutinib are safe and effective options. […] Clinical trial participation is essential to develop safer and more effective agents to treat WM. […] In the frontline setting, a series of randomized European trials are comparing chemoimmunotherapy regimens, such as cyclophosphamide, dexamethasone, and rituximab vs ibrutinib plus rituximab in the phase 2/3 RAINBOW trial or vs venetoclax plus rituximab in the phase 2 VIWA-1 study. […] In the relapsed setting, the phase 2 CLOVER-WaM study evaluating the radioconjugate iopofosine I-131 has completed accrual of patients, and results are expected soon. […] Given WM’s rarity, clinical trials are essential to advance the field, and multi-institutional collaboration is crucial.

• #2 Waldenstrom Macroglobulinemia Treatment & Management: Approach Considerations, Emergent Treatment, Pharmacologic Therapy

  https://emedicine.medscape.com/article/207097-treatment

  In 2015, ibrutinib (Imbruvica) became the first drug approved by the US Food and Drug Administration (FDA) for treatment of WM. […] In 2018, the FDA approved an expanded indication for ibrutinib in WM beyond its use as a monotherapy to include combination use with rituximab. […] Zanubrutinib (Brukinsa) became the second BTK inhibitor approved for Waldenstrm macroglobulinemia. […] The purine nucleoside analogues fludarabine and cladribine have demonstrated activity against Waldenstrm macroglobulinemia. […] Combination chemotherapy approaches have been explored, with response rates of more than 75%. […] Salvage therapy for patients with resistant disease or relapse includes the reuse or alternative use of front-line agent, combination therapy, thalidomide (with or without steroids), bortezomib, everolimus, alemtuzumab, and stem cell transplantation. […] High-dose chemotherapy with autologous peripheral blood cell transplantation is reserved for selected younger patients with primary refractory or relapsed disease.

• #2 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  The second generation BTK-Is, including zanubrutinib and acalabrutinib, have shown excellent activity in the relapsed WM setting and, in November 2021, zanubrutinib became the first of these agents to be approved by the European Medicines Agency for the treatment of WM. Following promising early-phase safety and efficacy data, a multi-centre phase 3 study, which randomised patients between ibrutinib and zanubrutinib, revealed zanubrutinib afforded similar responses to ibrutinib with less off-target toxicity. Although VGPR and CR rates improved with zanubrutinib (28% and 19%, respectively), this did not reach statistical significance (P=0.09). Across the molecular subgroups, median time to major response for both arms was 2.8 months; however, the median times to major response in patients with CXCR4WHIM mutations were 3.1 months in the zanubrutinib arm versus 6.6 months in the ibrutinib arm. Notably, atrial fibrillation was recorded in 15% of patients taking ibrutinib and in 2% of patients taking zanubrutinib, while hypertension was reported in 16% of patients taking ibrutinib and 11% patients of patients taking zanubrutinib. Grade 3 neutropenia was more common with zanubrutinib (20% versus 8%), but this did not translate to an increased number of grade >3 infections. Zanubrutinib may therefore be a preferred option in patients with a significant cardiac history.

• #2 Waldenstrom Macroglobulinemia: Tailoring Therapy for the Individual

  https://pmc.ncbi.nlm.nih.gov/articles/PMC9362871/

  The combination of rituximab cyclophosphamide and dexamethasone was introduced in 2007 and produced an overall response rate of 83%; PR in 74%. […] Bortezomib, rituximab, and dexamethasone was found to be highly effective in the treatment of macroglobulinemia. […] Carfilzomib is active in the treatment of macroglobulinemia without producing neuropathy. […] Ixazomib as a non-neurotoxic orally administered proteasome inhibitor offers obvious advantages in an elderly population. […] In a phase II trial, bendamustine with and without rituximab resulted in an overall response rate of 83.3% and a PFS of 13.2 months in relapsed refractory disease. […] Acalabrutinib is approved for the treatment of chronic lymphatic leukemia and mantle cell lymphoma. […] The abrupt withdrawal of ibrutinib because of toxicity or surgery can result in a rapid rise in the IgM level, flare, associated with an exacerbation in symptoms of macroglobulinemia. […] Although there is no single best initial therapy for patients with macroglobulinemia, ibrutinib is essential for those patients who have central nervous system involvement, the so-called Bing-Neel syndrome. […] The decision process for relapsed refractory disease is more complex.

• #2 Understanding the Treatment of Waldenström’s Macroglobulinemia – The ASCO Post

  https://ascopost.com/issues/september-25-2023/understanding-the-treatment-of-waldenstroem-s-macroglobulinemia/

  Ibrutinib proved to be a game changer in Waldenstrms macroglobulinemia, having yielded an overall response rate of 90% and a major response rate of 73% in the pivotal trial. […] The iNNOVATE trial suggested that the addition of rituximab could boost the effect of ibrutinib. […] The BTK inhibitor zanubrutinib has advanced the indefinite-duration approach. […] Use of the newer highly selective BTK inhibitor pirtobrutinib could change the conventional practice of not prescribing another BTK inhibitor after patients experience disease progression on a first one. […] The BCL2 inhibitor venetoclax may represent an additional option in this setting. […] Autologous stem cell transplantation remains an option for good-performance patients, especially those with limited treatment exposure who remain chemosensitive.

• #2 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  CAR-T cell therapy (MB-106) has been granted orphan drug status by the US Food and Drug Administration and is showing promising results in early phase trials. In a single-centre study for patients with RR indolent B-cell lymphoma, six patients with WM received the third-generation, fully human CD20 targeting CAR-T product (MB-106) and four patients underwent response assessment. This was a heavily pre-treated cohort (median 6.5 prior lines, all 4 patients were BTK-I refractory). Toxicity was manageable; no patients experienced grade 3 cytokine release syndrome and there was no immune effector cell-associated neurotoxicity. All patients responded to treatment: 2 achieved CR, 1 PR and 1 MR. Durability of response is awaited. […] Autologous stem cell transplantation is an option in selected chemo-sensitive patients at second line. In patients for whom this may be an option, drugs that impair stem cell mobilisation (fludarabine and chlorambucil) should be avoided. Allogeneic transplantation is an appropriate option in highly selected patients who are refractory to chemo-immunotherapy and BTK-Is.

• #2 Treatment Regimens and Considerations – International Waldenstrom’s Macroglobulinemia Foundation

  https://iwmf.com/treatment-regimens-and-considerations-1/

  The medications used to treat Waldenstrom macroglobulinemia can be given is a variety of combination and schedules. Most of the recommended regimens include rituximab (Rituxan®) and one or more chemotherapy drugs. […] There are four first-line therapy regimens currently preferred by both the WM experts of the National Comprehensive Cancer Network (NCCN) – an alliance of 30 leading cancer centers in the U.S. – and the international consensus panel of WM experts who participated at the tenth International Workshop for Waldenstrom Macroglobulinemia (IWWM-10). […] While the four therapy regimens listed above are preferred, there are many other regimens that are recommended for treatment as well. The choice of therapy should be guided by your clinical profile; any genetic mutations identified (for example, mutations in the MYD88 or CXCR4 genes); and drug availability.

• #2 Treatment for Waldenström macroglobulinaemia (WM) | Blood Cancer UK

  https://bloodcancer.org.uk/understanding-blood-cancer/lymphoma/waldenstrom-macroglobulinaemia/wm-treatment/

  The type of treatment youll need will depend on how far the Waldenstrm macroglobulinaemia (WM) has developed. […] If you dont have many symptoms when youre diagnosed, and the WM isnt affecting your general health or wellbeing, you may not need treatment straight away. Instead, youll be put on active monitoring also known as watch and wait and have regular check-ups every three to six months. […] If theres a large amount of IgM in your blood and it becomes too thick, plasma exchange treatment (also called plasmapheresis) can be used to help thin your blood to help it flow better through your blood vessels. […] Different types of drug work in different ways to control the LPL (cancer) cells. […] You will usually have a combination of two or three drugs to treat WM. […] Chemotherapy drugs are anti-cancer drugs which kill cancer cells or stop them growing.

• #2 Waldenström macroglobulinemia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/897

  Waldenstrm macroglobulinemia (WM) is a rare indolent B-cell lymphoma that most commonly occurs in older white men. […] WM is incurable but median overall survival is long (approximately 8 years based on US data, though this will have improved significantly with the use of Bruton tyrosine kinase inhibitors and other novel agents). […] Goals of treatment are to reduce symptoms, improve quality of life, and prolong survival. Treatment options include observation (for asymptomatic patients), plasmapheresis, chemotherapy, and targeted therapies. […] There is no standard of care, mainly due to a lack of randomized trials in WM. Participation in clinical trials is recommended where possible. […] Treatment recommendations from the Eighth International Workshop on Waldenstrm’s Macroglobulinemia.

• #3 Treatment for Waldenström Macroglobulinemia | Fred Hutchinson Cancer Center

  https://www.fredhutch.org/en/diseases/waldenstrom-macroglobulinemia/treatment.html

  Treatment for Waldenstrm macroglobulinemia (WM) differs from treatment for other types of lymphoma and must be tailored to each individual. Its important to be treated at a specialized center with expertise in WM. […] WM is treatable and may be controlled for a long time with expert care. […] Few studies have compared the medicines used for WM, so theres no single standard treatment. Your Fred Hutch physician will explain your options and recommend an individualized treatment plan based on the specifics of your disease as well as your overall health, personal preferences and other factors. […] If you have a high level of IgM in your blood that has made your blood thicker than normal and is causing symptoms (hyperviscosity syndrome), you may need plasma exchange (plasmapheresis). It can reduce the thickness of your blood and help relieve your symptoms.

• #3 Waldenstrom Macroglobulinemia Treatment & Management: Approach Considerations, Emergent Treatment, Pharmacologic Therapy

  https://emedicine.medscape.com/article/207097-treatment

  The US Food and Drug Administration (FDA) has approved an expanded indication for ibrutinib in WM beyond its use as a monotherapy to include combination use with rituximab. […] Autologous stem cell transplantation should be considered at the first or second relapse in select patients with chemosensitive disease, especially if the first remission duration is short ( 2 years). […] Treatment recommendations from the 10th International Workshop on Waldenstrm Macroglobulinemia are as follows: Alkylating drugs (bendamustine, cyclophosphamide) and proteasome inhibitors (bortezomib, carfilzomib, ixazomib), both in combination with rituximab, as well as BTK inhibitors (ibrutinib, zanubrutinib), alone or in combination with rituximab, are preferred first-line therapy options for symptomatic patients.

• #3 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  Bendamustine with rituximab (BR) is favoured in those needing rapid disease control (e.g. in patients needing rapid reduction in IgM paraprotein, management of cryoglobulinaemia or for management of bulky disease). In a frontline study that randomised patients with indolent non-hodgkin’s lymphoma between BR and RCHOP (rituximab, cyclophosphamide, vincristine and prednisolone), BR was superior in patients with WM, with a median PFS of 69.5 months. However, BR comes with an increased toxicity profile of grade 3 neutropenia and grade 3 infection. This led to frequent dose reductions in the trial. In a retrospective comparison of BR with DRC in both upfront and relapsed setting, BR showed a trend towards superior PFS (2-year PFS 88% vs. 61% (P=0.07) in the upfront BR and DRC groups, while 2-year PFS was 66% vs. 53%, (P=0.08) in the relapsed refractory setting. Patients should also be made aware of a small risk of alkylator-associated myeloid malignancy.

• #3 Current Therapeutic Options in Waldenstrom Macroglobulinemia

  https://touchoncology.com/haematological-malignancies/journal-articles/current-therapeutic-options-in-waldenstrom-macroglobulinemia/

  The discovery of the MYD88 mutation in WM has been a seminal event in shaping the treatment landscape for patients with WM. Ibrutinib is a first-in-class oral irreversible inhibitor of BTK which functions as a B-cell receptor signaling kinase, resulting in downstream activation of NFB, which in turn promotes cell proliferation and survival. […] Ibrutinib was first studied in a relapsed/refractory WM population and demonstrated substantial activity in MYD88MUT patients that resulted in its approval by the US Food and Drug Administration for WM. […] The substantial responses seen with ibrutinib therapy do come at the cost of unique toxicities and indefinite therapy. […] Proteasome inhibitor-based therapy represents another important treatment option for WM. Most notably, bortezomib-dexamethasone-rituximab (BDR) has been used in the frontline setting.

• #3 New treatment for Waldenstrom’s macroglobulinaemia in England – Cancer Research UK – Cancer Newsfacebook icontwitter iconlinkedin iconfacebook icontwitter iconinstagram iconlinkedin iconyoutube iconfundraising regulator icon

  https://news.cancerresearchuk.org/2022/10/01/new-treatment-for-rare-lymphoma-waldenstroms-macroglobulinaemia-in-england/

  The National Institute for Health and Care Excellence (NICE) has recommended zanubrutinib (Brukinsa) as an option for treating some people with Waldenstrom’s macroglobulinaemia (WM), a rare type of non-Hodgkin lymphoma (NHL) that develops in white blood cells. […] Zanubrutinib is now the first WM drug NICE has recommended for routine NHS use in England. It is likely that the decision will also apply to Wales and Northern Ireland. […] After comparing zanubrutinib to the main treatments currently used by NHS England, the NICE committee concluded that it was clinically effective and may help people with WM live longer and have a better quality of life. […] In making its decision, the committee called the routine use of zanubrutinib a “step-change” in managing WM. […] Current treatment options include chemotherapy and immunotherapy, but these can severely impact people’s quality of life. Patients told NICE they would therefore value more treatment options.

• #3 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  Rituximab maintenance therapy (monthly administration until toxicity or progressive disease) has been studied in patients following BR induction and has not been demonstrated to afford any progression-free or survival advantage. However, consolidative rituximab leads to deepening of response in one third of WM patients after completing rituximab-containing regimens and may be offered to those who have not achieved a very good partial response (VGPR) and to those whose chemoimmunotherapy was truncated. […] Bortezomib (weekly) in combination with rituximab and dexamethasone has been shown to be effective in both upfront and relapsed/refractory settings. In the upfront setting, 85% of patients responded (3% complete response (CR), 65% PR, 17% minor response). After a minimum follow-up of 32 months, median progression-free survival was 42 months. Peripheral neuropathy occurred in 46% of patients (grade 3 in 7% of patients); only 8% of patients discontinued bortezomib owing to neuropathy. Bortezomib should therefore be avoided in patients with WM-associated neuropathy.

• #4 Management of Waldenstrom’s macroglobulinaemia – The Pharmaceutical Journal

  https://pharmaceutical-journal.com/article/ld/management-of-waldenstroms-macroglobulinaemia

  BTK-Is have shown excellent responses in treatment-naïve and relapsed disease and are currently available as a treatment option at first relapse of WM in the UK. In a Phase II clinical trial, Ibrutinib was the first-in-class BTK antagonist showing excellent efficacy at a continuous dose of 420mg once daily. In the landmark phase 2 study in patients with previously treated WM, the objective response rate (ORR) was 90.5%, and the major response rate was 73.0%. Responses were greatest in those with MYD88L265P, CXCR4WT disease (100% ORR and 91.2% major response rate). Patients with MYD88L265P + CXCR4WHIM mutations had a slightly reduced response rate of 85.7%, and patients with MYD88WT had the lowest response rates at 71.4 %. The responses were rapid (median time to response = four weeks) and durable, with estimated two-year progression-free and overall survival rates among all patients of 69.1% and 95.2%, respectively. The main toxicities were haematological (grade >3 neutropenia 14%; grade >3 thrombocytopenia 13%). However, in a retrospective review of 112 ibrutinib-treated patients with WM (treatment durations = 43 months), 11% experienced atrial fibrillation.

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