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 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 11/01/2000 and 10/31/2019. The median follow-up was 4.5 (95%CI: 4-5) years. The R-Benda (n=83) cohort 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 versus 4.3 (DRC) and 1.8 years (BDR), p=0.0003].The time-to-next therapy (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. 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. This article is protected by copyright. All rights reserved.

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Authors: Jithma P Abeykoon, Saurabh Zanwar, Stephen M Ansell, Eli Muchtar, Rong He, Patricia T Greipp, Rebecca L King, Sikander Ailawadhi, Jonas Paludo, Jeremy T Larsen, Thomas M Habermann, David Inwards, Ronald S Go, Gita Thanarajasingam, Francis Buadi, Angela Dispenzieri, Carrie A Thompson, Thomas E Witzig, Martha Lacy, Wilson Gonsalves, Grzegorz S Nowakowski, David Dingli, S Vincent Rajkumar, Robert A Kyle, Taimur Sher, Vivek Roy, Allison Rosenthal, Asher A Chanan-Khan, Craig Reeder, Morie A Gertz, Shaji Kumar, Prashant Kapoor