Safety and Efficacy of Ibrutinib plus Rituximab in Relapsed Mantle-Cell Lymphoma
Single-agent ibrutinib has been approved by the FDA for patients with MCL who received at least 1 previous therapy based on a phase 2 clinical trial in which ibrutinib elicited a response rate of 68% (Wang ML, et al. N Engl J Med. 2013;369:507-516). In that study, there was a transient increase in circulating MCL lymphocytes during the initial phase of tumor reduction, which could be diminished by targeting the circulating MCL cells with intravenous RTX that would even further improve the efficacy of ibrutinib.
Wang and colleagues now report on a single-center phase 2 clinical trial with ibrutinib in combination with RTX for relapsed MCL, in which 50 patients received RTX 375 mg/m2 intravenously weekly 4 times during cycle 1 (cycle, 28 days), then on day 1 of every cycle from cycles 3 through 8, and thereafter once every other cycle up to 2 years. Ibrutinib was continuously orally dosed at 560 mg daily (Wang M, et al. Blood. 2014;124. Abstract 627).
With a median follow-up time of 6.5 months, 45 patients are evaluable for toxicity and efficacy and 33 patients (73% of evaluable patients) have Ki-67 of <50%. The ORR was 87% with complete remission (CR) in 17 (38%) patients and partial remission (PR) in 22 (49%) patients. The median duration of response and PFS have not been reached. Excluding 12 of the 45 evaluable patients with Ki-67 of ?50%, the ORR for 33 patients with relapsed/refractory MCL and lower Ki-67 (<50%) was 100% (48% for CR and 52% for PR).
In all, 8 patients are off study as a result of progressive MCL (4 patients never responded, 4 responded then progressed)—all had Ki-67 of >50%. Grade 3 hematologic toxicity events included neutropenia and thrombocytopenia. The most common grade 1/2 nonhematologic toxicity events included fatigue, diarrhea, myalgia, dyspnea, blurred vision, nausea, dry eye, and atrial fibrillation.
Although this trial is ongoing, the preliminary data indicate that the combination of ibrutinib and RTX is well-tolerated and is efficacious in patients with relapsed MCL, especially in those with Ki-67 of <50%.