IBCL-085: Assessment of Fixed-Duration Therapies for Treatment-Naïve Waldenström Macroglobulinemia

Context Waldenstrom macroglobulinemia (WM) is a rare lymphoma for which scant comparative data exist to guide frontline therapy. Objective To compare the efficacy of the most frequently used rituximab-based fixed-duration anti-WM regimens in routine practice [rituximab, bendamustine (R-Benda); dexamethasone, rituximab, cyclophosphamide (DRC); and bortezomib, dexamethasone, rituximab (BDR)] to inform clinicians about the benefits/limitations of choosing one regimen over the other. Design A retrospective cohort study. Participants Patients with active WM seen at Mayo Clinic Rochester, Arizona, and Florida campuses between 10/01/2000 and 10/31/2019 who received R-Benda, DRC, or BDR as primary therapy were included. Outcomes Measures Overall response rate (ORR), event-free survival (EFS), progression-free survival (PFS), overall survival (OS), time-to-next therapy (TTNT) and treatment related adverse-effects (AEs) based on the three treatment regimens. The MYD88L265P mutation status was assessed using allele-specific polymerase-chain-reaction (sensitivity 1%). Response rates were assessed by Consensus Criteria. Time-to-event analyses were performed from the frontline therapy, using Kaplan-Meier method. CTCAE v4.03 was used to grade toxicities. Results The study included 220 patients with active WM who were treated with R-Benda (n=83), DRC (n=92) or BDR (n=45). The median follow-up was 4.5 (95% CI: 4-5) years. The R-Benda cohort demonstrated superior ORR (98%), in comparison to DRC (78%) or BDR (84%) cohorts, p=0.003. Similarly, longer PFS was evident with R-Benda use [median 5.2 versus 4.3 (DRC) and 1.8 years (BDR), p=0.0003]. The TTNT favored R-Benda [median, not-reached, versus 4.4 (DRC) and 2.6 years (BDR), p=0.0002]. 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 MYD88 signature within each cohort. Toxicity profiles across the three groups were comparable, barring a higher incidence of neutropenia and neuropathy in patients who received R-Benda and BDR regimens, respectively. Conclusions The ORR, PFS and TTNT with R-Benda are superior compared to DRC or BDR in treatment-naive patients with active WM. The patient outcomes with any one of these three regimens are unaffected by the MYD88L265P mutation status.