Assessment of fixed-duration therapies for treatment-naïve Waldenström macroglobulinemia.

Comparative data guiding initial therapy for Waldenström macroglobulinemia (WM), an infrequently encountered non-Hodgkin lymphoma, are sparse. We evaluated three commonly used rituximab-based frontline regimens: rituximab-bendamustine (R-Benda); dexamethasone, rituximab, cyclophosphamide (DRC); and bortezomib, dexamethasone, rituximab (BDR) in 220 treatment-naïve patients with WM, seen at Mayo Clinic between November 1, 2000 and October 31, 2019. The median follow-up was 4.5 (95%CI: 4-5) years. The R-Benda cohort (n = 83) demonstrated superior overall response rate (ORR: 98%), in comparison to DRC (n = 92, ORR: 78%) or BDR (n = 45, ORR: 84%) cohorts, p = 0.003. Similarly, longer progression-free survival (PFS) was evident with R-Benda use [median 5.2 vs. 4.3 (DRC) and 1.8 years (BDR), p < 0.001]. The time-to-next therapy (TTNT) favored R-Benda [median, not-reached, 4.4 (DRC) and 2.6 years (BDR), p < 0.001). These endpoints were comparable between the DRC and BDR cohorts. Overall survival (OS) was similar across the three cohorts, p = 0.77. In a subset analysis of 142 patients genotyped for MYD88L265P mutation, the ORR, PFS and TTNT were unaffected by the patients' MYD88 signature within each cohort. In conclusion, ORR, PFS and TTNT with R-Benda are superior compared to DRC or BDR in treatment-naïve patients with active WM. The patient outcomes with any one of these three regimens are unaffected by the MYD88L265P mutation status.

IgM multiple myeloma: disease definition, prognosis, and differentiation from Waldenstrom's macroglobulinemia.

IgM multiple myeloma (MM) and Waldenstrom's macroglobulinemia (WM) are two distinct hematologic entities with the common finding of an IgM monoclonal gammopathy. Distinguishing these two diagnoses is critical as the approach to therapy is different. A priori, we defined IgM MM as a symptomatic clonal plasma cell proliferative disorder characterized by an IgM monoclonal protein (regardless of size), 10% or more plasma cells on bone marrow biopsy, plus the presence of lytic bone lesions and/or translocation t(11;14). Twenty-one patients met this definition of IgM MM. All 21 patients had lytic bone lesions. Of the 16 evaluated with FISH, 6 (38%) demonstrated t(11;14). Median overall survival was 30 months, which is similar to non-IgM myeloma patients treated during this period and shorter than what would be expected for WM. In this, the largest series of patients with IgM MM, we describe the clinical features and prognosis of patient with IgM MM using a strict definition for the disease. The subset of patients without lytic lesions or t(11;14) but with immunophenotypic features suggestive of MM need further study.