Lenalidomide, Bendamustine, and Rituximab as First-Line Therapy for Patients >65 Years with Mantle-Cell Lymphoma: Preliminary Results from the Nordic Lymphoma Group MCL4 (LENA-BERIT) Phase 1-2 Trial

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Mantle-cell lymphoma (MCL) is a disease of the elderly; the median age at diagnosis is 70 years. Currently, the standard therapy for elderly patients has not been defined. In this trial, Jerkeman and colleagues investigated whether the addition of lenalidomide (LEN) to bendamustine plus rituximab (BR) followed by LEN maintenance for 7 months would improve the efficacy and safety of treatment among older patients with MCL.

Patients with untreated stage II to stage IV MCL were enrolled in this phase 1/2 trial if they were older than 65 years or unable to tolerate high-dose chemotherapy. BR was given for 6 cycles every 4 weeks. In the first phase of the study, which included 24 patients, the maximum tolerated dose of LEN was established as 10 mg on days 1 to 14 during the induction cycles 2 to 6; LEN given during cycle 1 resulted in unexpected grade 3 or 4 cutaneous and allergic reactions. In the maintenance phase, single-agent LEN was given as follows: cycles 7 to 8, 10 mg on days 1 to 21; cycles 9 to 13, 15 mg on days 1 to 21.

The trial concluded after a total of 50 patients enrolled. The patients’ median age was 71 years. At the time of data presentation, 35 patients were evaluable for response after 6 months of LEN plus BR. The overall response rate was 97%, including 77% of patients who achieved complete response (CR) or CR unconfirmed. Of the 30 evaluable patients, 53% were minimal residual disease-negative after 6 months of LEN plus BR. The progression-free survival was reported as 42 months. The estimated 2-year progression-free survival and 2-year overall survival were 68% and 87%, respectively.

The most common nonhematologic adverse events included infection and cutaneous reactions. Among grade 3 or 4 infections, there were 6 febrile neutropenias, 6 pneumonias, and 1 sepsis. The LEN plus BR treatment was associated with prolonged CD4 depletion; after 13 months of therapy, the median CD4+ counts remained abnormal. In addition, 1 fatal pneumocystis pneumonia (PCP) infection was encountered, such that PCP prophylaxis was subsequently recommended. Furthermore, 1 cytomegalovirus  retinitis occurred after 6 cycles of treatment.

When omitted in cycle 1, LEN in combination with BR is feasible as first-line therapy in older patients with high-risk MCL. This combination is associated with a high response rate and a high rate of MRD negativity, as well as prolonged CD4 depletion, such that PCP prophylaxis is recommended. LEN + BR may be an effective treatment option for elderly patients with MCL.

References:

Jerkeman M, Albertsson-Lindblad A, Kolstad A, et al. Lenalidomide, bendamustine, and rituximab as first-line therapy for patients >65 years with mantle cell lymphoma: preliminary results from the Nordic Lymphoma Group MCL4 (LENA-BERIT) phase I-II trial. Poster presented at: American Society of Hematology (ASH) 2013 Annual Meeting; December 7-10, 2013; New Orleans, LA. Abstract 4377.

Last modified: March 25, 2014
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