Phase II Study Shows Durable Effect of Lenalidomide in Relapsed/Refractory Mantle Cell Lymphoma
In a phase II study (MCL-001, EMERGE) reported in Journal of Clinical Oncology, Andre Goy, MD, of Hackensack University Medical Center, and colleagues evaluated the use of single-agent lenalidomide (Revlimid) in bortezomib (Velcade)-treated patients who had relapsed/refractory mantle cell lymphoma. Durable responses were observed in 28% of patients.
Study Details
In this global multicenter study, 134 patients with mantle cell lymphoma who had relapsed or progressed after, or were refractory to, bortezomib were treated with lenalidomide 25 mg/d on days 1 to 21 every 28 days until disease progression or intolerance. The primary endpoints were overall response rate and duration of response.
Patients had a median age of 67 years (63% ≥ 65 years), 81% were male, 93% had stage III or IV disease, 87% had Eastern Cooperative Oncology Group performance status of 0 or 1, 22% had moderate to severe renal insufficiency, time to enrollment from diagnosis was ≥ 3 years in 61%, Mantle Cell Lymphoma International Prognostic Index score was intermediate in 38% and high in 29%. Forty-one percent of patients had marrow involvement, 57% had high tumor burden, 33% had bulky disease, 53% had received ≥ 4 prior systemic antilymphoma therapies, 60% were refractory to bortezomib, 33% had received prior high-dose or dose-intensive therapy, and 29% had received bone marrow or autologous stem cell transplantation. Time from last prior systemic antilymphoma therapy was < 6 months in 72%, and patients had received a median of 4 prior therapies (range 2 to 10).
Responses
On central review, 28% of patients had response, including complete response or unconfirmed complete response in 7.5%. Median duration of response and of complete/unconfirmed complete response was 16.6 months. At data cutoff, duration of response was ≥ 6 months in 18 patients and ≥ 12 months in 10 (maximum 29.2+ months). Response rate and duration of response were consistent across subgroups examined. Stable disease ≥ 6 months was observed in 11 patients, including 4 with stable disease ≥ 12 months. Most responses were reported after two to four cycles of lenalidomide, although some patients required up to 13 months of treatment to achieve best response. Among 111 patients with baseline and postbaseline data available, 77 (69%) experienced a reduction in tumor burden, including 46 (41%) with ≥ 50% reduction.
Median progression-free survival was 4.0 months, time to progression was 5.4 months, and time to failure was 3.8 months. After median follow-up of 9.9 months, median overall survival was 19.0 months. In total, 46% of patients received antilymphoma therapy after lenalidomide, with 13% of patients having response at the time of last analysis.
Toxicities
In total, 66% of patients had grade 3 or 4 adverse events, with the most common being neutropenia (43%), thrombocytopenia (28%), anemia (11%), pneumonia (8%), and fatigue (7%). Dose interruption occurred in 57% of patients, dose reduction due to adverse events in 38%, and discontinuation due to adverse events in 19%. The most common adverse events leading to dose reduction, interruption, or discontinuations were neutropenia and thrombocytopenia. Six patients had bleeding events, including gastrointestinal hemorrhage, but none were considered related to lenalidomide. At a median follow-up of 13.4 months, 6 second primary malignancies (4.5%) were reported, including 3 invasive malignancies (1 myelodysplastic syndrome in a patient with prior ASCT, 1 metastatic colon cancer, and 1 squamous cell carcinoma of skin metastasized to cervical lymph nodes), for an overall incidence rate of 2.21 per 100 person-years. The median time to second primary malignancy from the start of lenalidomide was 7.3 months (range 3.1–9.7 months).
The investigators concluded: “[The study] demonstrated rapid and prolonged efficacy of lenalidomide with a predictable safety profile in heavily pretreated responding patients with [mantle cell lymphoma] who had relapsed or progressed after or were refractory to prior therapies that included bortezomib. These findings support the clinical benefit of oral lenalidomide in heavily pretreated patients with [mantle cell lymphoma], including those with advanced-stage disease, regardless of tumor burden, and those with multiple prior therapies, including prior [autologous stem cell transplantation], thus providing evidence of an active treatment in this patient population after bortezomib.”
The study was supported by Celgene.
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