Carrie Thompson, Hong Fang, Morie A. Gertz, Ellen McPhail, Angela Dispenzieri, Jonas Paludo, Rebecca L. King, Nelson Leung, Rong He, Robert A. Kyle, Stephen M. Ansell, Martha Q. Lacy, Yi Lin, Wilson I. Gonsalves, Prashant Kapoor, Anne J. Novak, Thomas Habermann, Ronald S. Go, Betsy R. LaPlant, Craig B. Reeder, Taxiarchis Kourelis, Jithma P. Abeykoon, David Dingli, Alese E. Halvorson, Francis K. Buadi, Suzanne Hayman, Thomas E. Witzig, Shaji Kumar, S. Vincent Rajkumar, David Viswanatha
Waldenström macroglobulinemia (WM) is an immunoglobulin M-associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88L265P. Due to low prevalence of the wild-type (WT) MYD88 genotype in WM, clinically-relevant data in this patient-population are sparse, with one study showing nearly a 10-fold increased risk of mortality in this subgroup compared to patients with MYD88L265P mutation. We studied a large cohort of patients with MYD88L265P and MYD88WT WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016 to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88L265P mutation status, as determined by allele-specific polymerase chain reaction, was known in 219, and 174 (79%) of those exhibited MYD88L265P, 157 of 174 patients had active disease. Of 45 (21%) patients with MYD88WT genotype; 44 had active disease. The estimated median follow-up was 7.0 years; median overall survival was 10.2 years (95% CI: 8.4-16.5) for MYD88L265P vs. 13.9 years (95% CI: 6.4-29.3) for the MYD88WT (p=0.86). The time-to-next therapy from frontline treatment and the presenting features were similar in the two patient-populations. For patients with smoldering WM at diagnosis, the median time-to-progression to active disease was 2.8 years (95% CI: 2.2-3.8) in the MYD88L265P cohort and 1.9 years (95% CI: 0.7-3.1) in the MYD88WT cohort, (p=0.21). MYD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease-defining feature in WM. Our findings warrant external validation, preferably through prospective studies. This article is protected by copyright. All rights reserved.