Deepening of Response after Completing Rituximab-Containing Primary Therapy in Patients with Waldenstrom Macroglobulinemia

Abstract Introduction: Rituximab-containing regimens are commonly used for primary therapy in patients with symptomatic Waldenstrom macroglobulinemia (WM), and response is defined by decrease in serum IgM levels. In previous studies, we and others observed that in certain WM patients completing rituximab-based primary therapy, serum IgM levels continued to decline following completion of therapy, deepening the response to therapy. To further clarify the frequency and clinical characteristics, we evaluated a large population of treatment naive patients treated at our WM center with rituximab-containing regimens. Methods: Patients with a clinicopathological diagnosis of WM requiring therapy based on criteria from the 2ndInternational Workshop for WM (IWWM) who received a rituximab-containing regimen as primary therapy in the WM center at our institution from 2005 to 2016 were included. Responses were defined per criteria from the 6thIWWM. Findings were stratified based on patients having received, or not, maintenance therapy after induction therapy. We gathered pertinent clinical data, including responses at the end of induction, at the end of maintenance, and at the lowest serum IgM level after completion of induction and/or maintenance. Response deepening was defined as 25% decrease in serum IgM at any point after completion of therapy. Results: 179 patients met eligibility criteria for this study. Induction therapy consisted of bortezomib, dexamethasone and rituximab (BDR) (N=86; 48%); bendamustine and rituximab (Benda-R) (N=57; 32%); cyclophosphamide, dexamethasone and rituximab (CDR) (N=36; 20%). 117 (65%) patients received maintenance therapy. There were no differences in baseline characteristics for age, gender, serum IgM, hemoglobin level, bone marrow involvement, hemoglobin, platelet count, beta-2-microglobulin level, MYD88 and CXCR4 mutation status, time to therapy, regimen, and receipt of maintenance therapy vs. observation status. At baseline, median serum IgM levels for patients who received maintenance was 4,445 mg/dl (range 289-8,100 mg/dl) and for those who were observed was 4,400 mg/dl (range 155-10,020 mg/dl) (p=0.37). Following induction therapy, median serum IgM levels declined to 969 mg/dl (range 33-5,940 mg/dl) and 1,366 mg/dl (114-7,108 mg/dl) for patients who subsequently received maintenance or were observed (p Conclusion: A third of WM patients who receive primary therapy with rituximab-containing regimens experienced deepening of response following completion of therapy, with a median time to best response of 1.6 years. High serum IgM levels and bone marrow burden, low hemoglobin levels, and presence of CXCR4 mutations at primary therapy initiation were associated with lower odds of response deepening. Download : Download high-res image (228KB) Download : Download full-size image Disclosures Castillo: Genentech: Consultancy; Beigene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Millennium: Research Funding; Pharmacyclics: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Hunter: Pharmacyclics: Consultancy. Treon: Janssen: Consultancy, Other: Travel, Accommodations, Expenses; BMS: Research Funding; Johnson & Johnson: Consultancy; Pharmacyclics: Consultancy, Other: Travel, Accommodations, Expenses, Research Funding.