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Clonal hematopoiesis is associated with increased risk of progression of asymptomatic Waldenstrom macroglobulinemia.

ABSTRACT: Clonal hematopoiesis (CH) is associated with adverse outcomes in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma undergoing autologous stem cell transplantation. Still, its implications for patients with indolent NHL have not been well studied. We report the prevalence of CH in patients with Waldenström macroglobulinemia (WM) and its association with clinical outcomes. To unambiguously differentiate CH mutations from those in the WM clone, CH was defined by the presence of somatic mutations in DNMT3A, TET2, or ASXL1 (DTA) and was detected in 14% of 587 patients with IgM monoclonal gammopathy of undetermined significance (MGUS), smoldering WM (SWM) or WM. The presence and size of DTA clones were associated with older age. Patients with CH had an increased risk of progression from MGUS or SWM to WM, but not worse overall survival in this cohort. These findings further illuminate the clinical effects of CH in patients with indolent NHL such as WM.

SUBMITTER: Tahri S

PROVIDER: S-EPMC9006277 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Clonal hematopoiesis is associated with increased risk of progression of asymptomatic Waldenström macroglobulinemia.

Tahri Sabrin S Mouhieddine Tarek H TH Redd Robert R Lampe Luisa L Nilsson Katarina I KI El-Khoury Habib H Su Nang Kham NK Nassar Amin H AH Adib Elio E Bindra Govind G Abou Alaiwi Sarah S Trippa Lorenzo L Steensma David P DP Castillo Jorge J JJ Treon Steven P SP Ghobrial Irene M IM Sperling Adam S AS

Blood advances 20220401 7

Clonal hematopoiesis (CH) is associated with adverse outcomes in patients with non-Hodgkin lymphoma (NHL) and multiple myeloma undergoing autologous stem cell transplantation. Still, its implications for patients with indolent NHL have not been well studied. We report the prevalence of CH in patients with Waldenström macroglobulinemia (WM) and its association with clinical outcomes. To unambiguously differentiate CH mutations from those in the WM clone, CH was defined by the presence of somatic ...[more]

PMID: 34847227

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Project description:ImportanceWaldenström macroglobulinemia (WM), an IgM-associated lymphoplasmacytic lymphoma, has witnessed several practice-altering advances in recent years. With availability of a wider array of therapies, the management strategies have become increasingly complex. Our multidisciplinary team appraised studies published or presented up to December 2015 to provide consensus recommendations for a risk-adapted approach to WM, using a grading system.ObservationsWaldenström macroglobulinemia remains a rare, incurable cancer, with a heterogeneous disease course. The major classes of effective agents in WM include monoclonal antibodies, alkylating agents, purine analogs, proteasome inhibitors, immunomodulatory drugs, and mammalian target of rapamycin inhibitors. However, the highest-quality evidence from rigorously conducted randomized clinical trials remains scant.Conclusions and relevanceRecognizing the paucity of data, we advocate participation in clinical trials, if available, at every stage of WM. Specific indications exist for initiation of therapy. Outside clinical trials, based on the synthesis of available evidence, we recommend bendamustine-rituximab as primary therapy for bulky disease, profound hematologic compromise, or constitutional symptoms attributable to WM. Dexamethasone-rituximab-cyclophosphamide is an alternative, particularly for nonbulky WM. Routine rituximab maintenance should be avoided. Plasma exchange should be promptly initiated before cytoreduction for hyperviscosity-related symptoms. Stem cell harvest for future use may be considered in first remission for patients 70 years or younger who are potential candidates for autologous stem cell transplantation. At relapse, retreatment with the original therapy is reasonable in patients with prior durable responses (time to next therapy ≥3 years) and good tolerability to previous regimen. Ibrutinib is efficacious in patients with relapsed or refractory disease harboring MYD88 L265P mutation. In the absence of neuropathy, a bortezomib-rituximab-based option is reasonable for relapsed or refractory disease. In select patients with chemosensitive disease, autologous stem cell transplantation should be considered at first or second relapse. Everolimus and purine analogs are suitable options for refractory or multiply relapsed WM. Our recommendations are periodically updated as new, clinically relevant information emerges.

Dataset Information

Clonal hematopoiesis is associated with increased risk of progression of asymptomatic Waldenstrom macroglobulinemia.

Publications

Clonal hematopoiesis is associated with increased risk of progression of asymptomatic Waldenström macroglobulinemia.

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