A phase I/II study of lenalidomide (Len) in combination with rituximab (R) in relapsed/refractory mantle cell lymphoma (MCL) with early evidence of efficacy

Abstract

8030 Background: MCL remains a therapeutic challenge. R targets CD20 antigen on MCL cells while Len may target the microenvironment of MCL cells and enhance the ADCC activity of R. To test this hypothesis, we initiated a single-center; open label, phase I/II study. We now report the completed phase I. Methods: Eligible patients (pts) had 1–4 lines of prior therapy including prior thalidomide or R, regardless of resistance. Each cycle of treatment consisted of Len given orally daily on days 1–21 of a 28-day cycle and R 375 mg/m2 by IV infusion weekly for 4 weeks. A standard 3+3 dose escalation was used to determine MTD with Len doses at 10 mg, 15 mg, 20 mg, and 25 mg. DLT was defined as grade (G) 3 or 4 non-hematologic or G4 hematologic toxicity during the first cycle. Results: The phase I portion completed enrollment with 15 pts (4 at 10 mg, 3 at 15 mg, 6 at 20 mg and 2 at 25 mg). Thirteen pts were evaluable. Median age was 73 (62–84); median prior lines of therapy were 3 (1–4); median cycles received to date were 2 (1–7). Two DLT's occurred at 25 mg. One pt had G3 hypercalcemia. The other had G4 neutropenic fever and died of sepsis (G5) during the first cycle. Three additional pts were therefore enrolled at 20 mg. Common non-hematologic toxic events included pruritis (21 G1–2), hypercalcemia (9 G1–2, 1 G3), fatigue (9 G1–2), constipation (8 G1), diarrhea (6 G1–2), fever (6 G1–2), myalgias (4 G1–2, 1 G3) and elevated LDH (4 G1–2, 1 G3). Hematologic events included neutropenia (20 G1–2, 4 G3), thrombocytopenia (6 G1–2, 2 G3) and anemia (6 G1). There were no responses at 10 mg or 15 mg. At 20 mg after 2 cycles, 5 out of 6 pts achieved responses including 1 CR, 1 PR, 3 minor responses (MRs) and only 1 pt progressed. The 1 pt with PR went on to achieve a CR after 6 cycles. The 3 pts with MRs had tumor reductions by 43%, 40% and 38% respectively. These 3 patients with MRs continue to receive Len and might later achieve PR or CR. Conclusions: The MTD for Len with R in relapsed/refractory MCL was 20 mg, orally daily on days 1–21 of a 28-day cycle. Responses observed at 20 mg are promising with a favorable toxicity profile and are being evaluated further in an ongoing phase II study. [Table: see text]