Bouabdallah, Réda

Abstract Introduction: Diffuse large-B-cell lymphoma (DLBCL) is the most common of the non-Hodgkin lymphomas (NHL). Patients with DLBCL who are not cured by treatment with R-CHOP chemotherapy or high-dose chemotherapy with autologous stem cell rescue have a poor prognosis. These patients reflect a clear unmet need in the treatment of DLBCL. A previous sub-analysis of a phase II trial (NHL-002) of lenalidomide in patients with relapsed or refractory DLBCL, demonstrated a 19% overall response rate (ORR) with a 7-month median duration of response (DR). A confirmatory international phase II trial (NHL-003) of single-agent lenalidomide was initiated for patients with relapsed/refractory aggressive NHL that had received at least one prior treatment and had measurable disease. Herein, we report the data from the DLBCL patients enrolled in this trial. Methods: Patients received 25 mg oral lenalidomide once daily on days 1–21 of every 28-day cycle and continued therapy until disease progression or toxicity. The 1999 IWLRC methodology was used to assess response and progression. Results: This report focuses on the 73 DLBCL patients that were enrolled and evaluable for response assessment. The median age was 67 (21–87) years and 49 (67%) patients were male. Median time from diagnosis to lenalidomide treatment was 2 (0–18.6) years, and patients had received a median of 3 (1–6) prior treatment regimens. The ORR to lenalidomide was 29% (21/73), with 4% complete response (3/73) and 25% partial response (18/73). Eleven patients (15%) had stable disease. The most common grade 3 or 4 adverse events were neutropenia (32%), thrombocytopenia (15%), asthenia (8%) and anemia (7%). Conclusion: These results of this international study confirm that lenalidomide is active in heavily pre-treated patients with relapsed or refractory DLBCL with manageable side effects.

Abstract Introduction: Mantle-cell lymphoma (MCL) is an aggressive B-cell lymphoma that if not cured with aggressive chemoimmunotherapy and stem cell transplant is usually fatal. The intravenous proteasome inhibitor bortezomib produces an overall response rate (ORR) of 33% in patients with relapsed MCL (J Clin Oncol2006;24(30):4867–74). Unfortunately, most patients eventually relapse and new agents are needed for this disease. Two recently conducted phase II trials (NHL-002 and NHL-003) tested single-agent lenalidomide for patients with relapsed MCL. Fifty-four patients with MCL were enrolled into the two studies; 26% (14/54) had received prior bortezomib and they are the subject of this report. Methods: Patients with relapsed or refractory MCL and measurable disease 2 cm after at least one prior treatment regimen including prior bortezomib were eligible. Patients received 25 mg of lenalidomide orally once daily on days 1–21 of every 28-day cycle. Therapy was continued as tolerated or until disease progression. The 1999 IWLRC methodology was used to assess response and progression. Results: The 14 patients in this study were heavily pretreated with a median of 4 (2–6) prior treatments (including bortezomib) and 50% were bortezomib-refractory. Median age was 66 (45–84) years and 6 (43%) patients were female. Median time from diagnosis to lenalidomide treatment was 3.3 (0.7–7.6) years. The ORR with lenalidomide was 57% (8/14), including 21% (3/14) complete response (CR)/unconfirmed CR and 36% (5/14) partial responses. One (7%) patient had stable disease. The most common grade 3 or 4 adverse events were neutropenia (50%), thrombocytopenia (43%), anemia (21%), fatigue (21%), and leukopenia (21%). Neutropenic fever occurred in 7% of patients. Conclusion: These results demonstrate that lenalidomide oral monotherapy is very effective with manageable side effects in patients with relapsed or refractory MCL who had received prior treatment with bortezomib.

Abstract Introduction: Mantle-cell lymphoma (MCL) is a type of B-cell non-Hodgkin lymphoma (NHL) that typically responds to initial chemo-immunotherapy, but with a relatively short duration of response (DR) and progression-free survival (PFS) when treated with conventional chemotherapy agents. Although the overall survival (OS) of MCL has improved, most patients are not cured and new agents are needed. A sub-analysis of a recent phase II trial (NHL-002) investigating the efficacy and safety of lenalidomide in patients with relapsed or refractory MCL, demonstrated a promising overall response rate (ORR) of 53% with a median DR of 11.9 months. A confirmatory international phase II trial (NHL-003) of single-agent lenalidomide was initiated for patients with relapsed/refractory aggressive NHL that had received at least one prior treatment and had measurable disease. In this report, we analyze the current results from the MCL patients enrolled in this trial. Methods: Patients with relapsed or refractory MCL and measurable disease ≥2 cm after at least 1 prior treatment regimen were eligible. Patients received 25 mg of lenalidomide orally once daily on days 1–21 of every 28-day cycle. Patients continued therapy until disease progression or toxicity. The 1999 IWLRC methodology was used to assess response and progression. Results: This report focuses on the 39 MCL patients that were enrolled and evaluable for response assessment. Median age was 66 (33–82) years and 29 (74%) patients were male. Median time from diagnosis to lenalidomide treatment was 3.4 (0.4–9) years. Patients had received a median of 3 (1–8) prior treatments, and 23% (9/39) of patients had received prior bortezomib treatment. The ORR with lenalidomide was 41% (16/39), including 13% (5/39) complete response (CR)/unconfirmed CR, and 28% (11/39) partial responses. Ten (26%) patients had stable disease. The most common grade 3 or 4 adverse events were neutropenia (51%) and thrombocytopenia (25%), anemia (13%), fatigue (10%) and febrile neutropenia (10%). Conclusion: These results confirm that lenalidomide oral monotherapy is effective in the treatment of patients with relapsed or refractory MCL, with manageable side effects.