Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia

Castillo, Jorge J.; Advani, Ranjana H.; Branagan, Andrew R.; Buske, Christian; Dimopoulos, Meletios A.; D’Sa, Shirley; Kersten, Marie José; Leblond, Véronique; Minnema, Monique C.; Owen, Roger G.; Palomba, M. Lia; Talaulikar, Dipti; Tedeschi, Alessandra; Trotman, Judith; Varettoni, Marzia; Vos, Josephine M.I.; Treon, Steven P.

doi:10.1016/s2352-3026(20)30224-6

Cited by 115 publications

(118 citation statements)

References 69 publications

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“…41 Taken together, these data support the recent consensus guidelines that recommend continuing ibrutinib until the subsequent therapy, plus consideration of bridging, in ibrutinib-resistant WM patients. 42 Clinical trials should also consider allowing shorter wash-out periods or overlap of ibrutinib for WM patients in this clinical scenario.…”

Section: Discussionmentioning

confidence: 99%

Natural history of Waldenström macroglobulinemia following acquired resistance to ibrutinib monotherapy

et al. 2021

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Ibrutinib is highly active and produces long-term responses in patients with Waldenström macroglobulinemia (WM), but acquired resistance can occur with prolonged treatment. We therefore evaluated the natural history and treatment outcomes in 51 WM patients with acquired resistance to ibrutinib monotherapy. The median time between ibrutinib initiation and discontinuation was 2 years (range, 0.4-6.5). Following discontinuation of ibrutinib, a rapid increase in serum IgM level was observed in 60% (29/48) of evaluable patients, of whom 10 acutely developed symptomatic hyperviscosity. Forty-eight patients (94%) received salvage therapy after ibrutinib. The median time to salvage therapy after ibrutinib cessation was 18 days (95% CI 13-27). The overall and major response rates to salvage therapy were 56% and 44%, respectively, and the median duration of response was 48 months (95% CI 34-not reached). Quadruple-class (rituximab, alkylator, proteasome inhibitor, ibrutinib) exposed disease (OR 0.20, 95% CI 0.05-0.73) and salvage therapy 07 days after discontinuing ibrutinib (OR 4.12, 95% CI 1.07-18.9) were identified as independent predictors of a response to salvage therapy. The 5-year overall survival (OS) following discontinuation of ibrutinib was 44% (95% CI 26-75%). Response to salvage therapy was associated with better OS after ibrutinib (HR 0.08, 95% CI 0.02-0.38). TP53 mutations were associated with shorter OS, while acquired BTKC481S mutations had no impact. Our findings reveal that continuation of ibrutinib until subsequent treatment is associated with improved disease control and clinical outcomes.

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Section: Discussionmentioning

confidence: 99%

Natural history of Waldenström macroglobulinemia following acquired resistance to ibrutinib monotherapy

et al. 2021

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“…For the refractory and relapse cases, splenectomy, vinca alkaloids, azathioprine, and highdose intravenous gamma-globulin therapy may not work. According to the National Comprehensive Cancer Network (NCCN) guideline, the preferred regimens for WM include bendamustine/rituximab (BR), bortezomib/dexamethasone/rituximab (BRD), ibrutinib ± rituximab (I ± R), and rituximab/cyclophosphamide/dexamethasone (BCD), which can achieve > 80% e cacy 7 .…”

Section: Discussionmentioning

confidence: 99%

First Report of Eltrombopag Induced Severe Autoimmune Hemolytic Anemia in the Management of Waldenström Macroglobulinemia-associated Autoimmune Thrombocytopenia

Shen

Ye³

et al. 2021

Preprint

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Background: Autoimmune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA) can be observed in Waldenström Macroglobulinemia (WM). The cause of AIHA should be carefully distinguished during the disease management. Case Presentation: A 63-year-old female WM patient complicated with thrombocytopenia, who was admitted to our department with a complaint of abdominal pain. After first half of bortezomib/dexamethasone/rituximab (BRD) chemotherapy, her platelet level recovered, but subsequently decreased to extremely low level (around 1-2×109/L), and the patient suffered from platelet transfusion refractoriness. During the management of refractory thrombocytopenia, the patient developed severe hemolytic anemia, and further tests confirmed warm AIHA. FcγRIIα polymorphism test showed that the patient had FcγRIIα-131RH, which implied that the AIHA may not be WM-related. Given the effects of ibrutinib in controlling WM, ibrutinib single treatment was started, which quickly corrected the thrombocytopenia within five days, but not hemolysis. With a relatively safe platelet level, eltrombopag was stopped, and the hemolysis alleviated within three days after eltrombopag withdrawal. Conclusion: This is the first report on eltrombopag-induced AIHA, and we should always keep in mind of the drug induced hemolysis even in disorders with autoimmune background.

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“…The National Comprehensive Cancer Network has recently published its consensus recommendations on diagnosis and therapy of WM 150 . Recent consensus reviews on WM are available 96,151‐155 …”

Section: Managementmentioning

confidence: 99%

Waldenström macroglobulinemia: 2021 update on diagnosis, risk stratification, and management

Gertz

2021

American J Hematol

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Disease Overview: Waldenström macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with immunoglobulin M (IgM) monoclonal protein. Clinical features include anemia, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and rarely hyperviscosity. Diagnosis: Presence of IgM monoclonal protein associated with ≥10% clonal lymphoplasmacytic cells in bone marrow confirms the diagnosis. The L265P mutation in MYD88 is detectable in more than 90% of patients and is found in the majority of IgM MGUS patients. Risk Stratification: Age, hemoglobin level, platelet count, β 2 microglobulin, LDH and monoclonal IgM concentrations are characteristics that are predictive of outcomes. Risk-Adapted Therapy: Not all patients who fulfill WM criteria require therapy; these patients can be observed until symptoms develop. Rituximab-monotherapy is inferior to regimens that combine it with bendamustine, an alkylating agent, a proteosome inhibitor, or ibrutinib. Purine nucleoside analogues are active but usage is declining in favor of less toxic alternatives. The preferred Mayo Clinic induction is rituximab and bendamustine. Management of Refractory Disease: Bortezomib, fludarabine, thalidomide, everolimus, Bruton Tyrosine Kinase inhibitors, carfilzomib, lenalidomide, and bendamustine have all been shown to have activity in relapsed WM. Given WM's natural history, reduction of therapy toxicity is an important part of treatment selection. PATIENT A 55-year-old male was found to have an IgM monoclonal gammopathy in January 2001. He was observed until November 2006 when his IgM level climbed to 9135 mg/dL. He was treated with rituximab, bortezomib and dexamethasone for 4 months. Treatment was interrupted due to neuropathy, but the IgM level fell to 1150 mg/dL. He was observed until April 2011. At the time of progression his IgM was 11 500 mg/dL and he was treated with single agent rituximab. At that time he was found to have acquired von Willebrand disease. Rituximab failed to produce a minor response so he was placed on a trial of bendamustine, lenalidomide and rituximab. His response lasted less than 1 year. In 2014 he was placed on an experimental trial of oprozomib. This resulted in a response of 5 years duration. At relapse in August of 2019 he was placed on a trial of ixazomib and ibrutinib. Ixazomib was poorly tolerated due to diarrhea and he continued on ibrutinib alone. He has now been on ibrutinib 15 months and has achieved a very good partial response.

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Consensus treatment recommendations from the tenth International Workshop for Waldenström Macroglobulinaemia

Cited by 115 publications

References 69 publications

Natural history of Waldenström macroglobulinemia following acquired resistance to ibrutinib monotherapy

Natural history of Waldenström macroglobulinemia following acquired resistance to ibrutinib monotherapy

First Report of Eltrombopag Induced Severe Autoimmune Hemolytic Anemia in the Management of Waldenström Macroglobulinemia-associated Autoimmune Thrombocytopenia

Waldenström macroglobulinemia: 2021 update on diagnosis, risk stratification, and management

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