Predictive Factors for Response and Progression after Treatment with Rituximab in Previously Untreated Patients with Waldenstrom’s Macroglobulinemia (WM).

Abstract Introduction: Rituximab is an active agent for the treatment of WM. However many patients do not respond to this agent and several others develop secondary resistance. The purpose of this study was to identify clinical and laboratory parameters which could predict a higher likelihood of benefit in previously untreated WM patients who received treatment with rituximab. Patients and methods: We evaluated clinical and laboratory characteristics of 35 patients with WM who received primary treatment with single agent rituximab. We correlated these characteristics with response to treatment and time to progression. Results: Between 8/98 and 12/03, 35 WM patients, median age 68 (range 39–90), 24 male, received primary treatment with extended rituximab as previously described (Dimopoulos et al, JCO 2002 and Treon et al, Ann Oncol 2005). Anemia (Hgb<10g/dL) was present in 55%, thrombocytopenia (PLT<100,000/mm3) in 31%, lymphadenopathy in 40%, splenomegaly, hyperviscosity and B-symptoms were present in 17% of the patients each. 43% of the patients had M-peak levels 4gr/dL, 37% had albumin <3.5g/dL and 56% had 2 microglobulin >3,5mg/dL. Fifteen patients (43%) achieved at least 50% reduction of M-peak and of tumor infiltrates at all involved sites. Patients with Hg10 g/dL and monoclonal kappa light chain had a significantly higher probability to respond [65% vs 22% (pvalue 0.01) and 50% vs 10 % (p value 0,037) respectively]. Patients with higher albumin and lower serum M-peak levels had also a higher frequency of response (p=0,15 and 0,09 respectively). After a median follow-up of 43 months, 19 patients have progressed, (5 responders and 14 non responders) with a median PFS of 23,6 months for the whole patient population and not reached for the responders (75% without progression at 26 months). In the univariate analysis the most important factor predicting longer PFS was hemoglobin 10gr/dL (median 57,8 vs 5,4 months). Other factors associated with longer PFS was albumin 3,5gr/L (median 25,5 vs 5,3 months), serum M-peak <4gr/L (48 vs 6,2), absence of hyperviscosity (23 vs 3,5) and presence of k light chain (25,4 vs 5,1). Conclusion: Our analysis which included a large number of patients with long-term follow-up indicates that primary treatment with rituximab is associated with objective response in 43% of patients with WM and with a median PFS of 2 years. Patients most likely to benefit from rituximab include those without significant anemia, with k light chain, with lower levels of M-peak and with higher levels of albumin.