Disease Characteristics, Treatment Patterns, and Patient Outcomes of Lymphoplasmacytic Lymphoma or Waldenstroms Macroglobulinemia: A Single Institution Retrospective Review
Authors: Bufalino Shams B , Patel Malini M , Kruczek Kimberly R , Nasraty Farah E , Parini Vamsi , Joyce Cara , Smith Scott E 
Published: October 2019

Abstract
Title:
Disease Characteristics, Treatment Patterns, and Patient Outcomes of Lymphoplasmacytic Lymphoma or Waldenstroms Macroglobulinemia: A Single Institution Retrospective Review
Introduction:
Non-Hodgkin lymphomas (NHL) are a heterogeneous group of B-cell lymphoproliferative disorders, with certain subtypes progressing rapidly and requiring immediate treatment and others having a more indolent course. Lymphoplasmacytic lymphoma (LPL) or Waldenstroms macroglobulinemia (WM) is classified as an indolent lymphoma with a natural disease course involving multiple episodes of relapse and remission. Although a wide variety of acceptable treatment strategies exist in both the front line and relapsed settings, there are limited data for the clear recommendation of optimal treatment. We sought to determine if the choice of initial treatment of WM would have an effect on overall survival and cause of death.
Methods:
A retrospective chart review identified 52 patients diagnosed with LPL or WM between January 2006 and January 2016. Seven patients were excluded due to incomplete data, yielding a total of 45 patients over a 10-year period. Data regarding age, sex, comorbidities, Eastern Cooperative Oncology Group (ECOG) performance status, IgM level at diagnosis, initial therapy, progression free survival, overall survival, and cause of death were collected. Patient demographics and treatment characteristics were calculated overall, and by three outcomes of interest: relapse free survival, treatment-related death, and all-cause mortality. Cox proportional hazard models adjusted for age, gender, and comorbidities were used to estimate the hazard ratios and 95% confidence intervals for events associated with initial therapy.
Results:
Of the 45 patients with WM, the average age of diagnosis was 66.9 (standard deviation: 12.3) and 23 patients (51.1%) were male. The majority of patients had an ECOG status of 2 or less at time of diagnosis (n=39, 86.7%). Thirty-five patients had data regarding IgM level at diagnosis, of which 15 (42.9%) were greater than 3000 mg/dl. The majority of patients (n=39, 86.7%) went on to receive treatment with chemotherapy. Among the patients who received treatment, 9 (23%) patients received rituximab therapy alone while 11 (28%) patients received fludarabine-based regimens. Twenty-four patients (61.5%) received rituximab as either monotherapy or as part of a chemotherapy combination while 14 (35.9%) did not receive rituximab at all. Fludarabine-based initial therapy was significantly protective against relapse (hazard ratio: 0.19, 95% CI: 0.04-0.87). Initial therapy that included rituximab was also protective of relapse, though not statistically significant (hazard ratio: 0.37, 95% CI: 0.13-1.10). At the conclusion of our review, 13 patients (29%) had died. Cause of death was considered treatment related in 3 of these patients: 2 patients developed myelodysplastic syndrome and 1 patient developed acute myeloid leukemia. All three patients had received fludarabine-based chemotherapy in the first line or subsequent setting.
Conclusions:
Our data suggest that fludarabine-based chemotherapy for initial management of LPL or WM resulted in improved progression free survival when compared to other chemotherapy regimens. We observed a trend toward improvement in progression free survival in patients that received chemotherapy that included rituximab. Interestingly, all patients that died of a treatment related myeloid toxicity had received fludarabine-based chemotherapy as an initial or as a subsequent therapy. We can conclude that while the use of fludarabine in treatment of LPL or WM results in a longer disease free interval, one should be cognizant of the risk of secondary hematologic malignancies. Rituximab or rituximab-based treatment for this low grade lymphoma remains a practical option.

Disclosures
No relevant conflicts of interest to declare.