Non-Pegylated Lyposomal Doxorubicin, Cyclophosphamide, Vincristine, Prednisone and Rituximab (R-COMP) as Initial Treatment for Patients with Splenic Marginal Zone Lymphoma (SMZL). A GISL Study

Background: SMZL is an indolent lymphoma, presenting with massive splenomegaly generally associated with intrasinusoidal bone marrow infiltration. The encapsulation of doxorubicin into non-pegylated liposomes allows targeting of the drug to affected organs including spleen, lymphnodes and bone marrow.

Methods: In 2005 the GISL started a phase II study for the treatment of patients with histologically confirmed SMZL, investigating safety and clinical profile of 6 courses of a modified R-CHOP regimen in which standard doxorubicin was substituted with non pegylated lyposomal doxorubicin (NPLD) used at the same doses (50mg/m2) (R-COMP). Main inclusion criteria were age > 18 yrs, normal cardiac function and active disease (at least one of the following; Hb <10g/dl; plt <100.000/mmc, symptomatic splenomegaly, elevated LDH, B symptoms, extrasplenic disease, LDT <12 months). Splenectomy was allowed prior to treatment start only in case of symptomatic spleen enlargement. The study was planned according to a two-stage Simon design using overall response rate as primary endpoint. We present the results of the analysis performed after the completion of study stage 1. The access to stage 2 is allowed if at least 12 responses are recorded among among the first 19 evaluable cases.

Results: As of January 2007, 20 patient were enrolled with the following characteristics; median age 63 years (30–80), Hb <10g/dl in 20%, Lymphocytes > 5000/mmc in 65%, elevated LDH in 65%; 2 patients were splenectomized before treatment start. One patient was not available for response assessment. A clinical response was observed in all remaining 19 cases (ORR 100%); 12 (63%) cases obtained a CR. So far only one patient progressed at +1 month from treatment. Treatment was well tolerated with grade III/IV neutropenia in 8 patients (42%), grade III pulmonary toxicity in 1 patient and grade II peripheral neuropathy in 5 cases. In one case a reversible cardiac failure was reported after 1 month from the end of treatment.

Conclusions: In conclusion 6 cycles of R-COMP combination represent a safe and promising treatment option for patients with clinically active SMZL.