Glen Justice

Lenalidomide Monotherapy in Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

PURPOSE The major cause of death in aggressive lymphoma is relapse or nonresponse to initial therapy. Lenalidomide has activity in a variety of hematologic malignancies, including non-Hodgkins lymphoma (NHL). We report the results of a phase II, single-arm, multicenter trial evaluating the safety and efficacy of lenalidomide oral monotherapy in patients with relapsed or refractory aggressive NHL. PATIENTS AND METHODS Patients were treated with oral lenalidomide 25 mg once daily on days 1 to 21, every 28 days, for 52 weeks, until disease progression or intolerance. The primary end point was response; secondary end points included duration of response, progression-free survival (PFS), and safety. RESULTS Forty-nine patients with a median age of 65 years received lenalidomide in this study. The most common histology was diffuse large B-cell lymphoma (53%), and patients had received a median of four prior treatment regimens for NHL. An objective response rate of 35% was observed in 49 treated patients, including a 12% rate of complete response/unconfirmed complete response. Responses were observed in each aggressive histologic subtype tested (diffuse large B-cell, follicular center grade 3, mantle cell, and transformed lymphomas). Of patients with stable disease or partial response at first assessment, 25% improved with continued treatment. Estimated median duration of response was 6.2 months, and median PFS was 4.0 months. The most common grade 4 adverse events were neutropenia (8.2%) and thrombocytopenia (8.2%); the most common grade 3 adverse events were neutropenia (24.5%), leukopenia (14.3%), and thrombocytopenia (12.2%). CONCLUSION Oral lenalidomide monotherapy is active in relapsed or refractory aggressive NHL, with manageable side effects.

Lenalidomide oral monotherapy produces a high response rate in patients with relapsed or refractory mantle cell lymphoma

Mantle cell lymphoma (MCL) is an aggressive non‐Hodgkin lymphoma with a poor prognosis following first relapse. We present a subgroup analysis of an open‐label phase II trial investigating the efficacy and safety of lenalidomide in patients with relapsed or refractory MCL. Oral lenalidomide 25 mg was self‐administered once daily on days 1–21 every 28 d for up to 52 weeks, according to tolerability or until disease progression. The primary endpoint was overall response rate (ORR) and secondary endpoints were duration of response, progression‐free survival (PFS) and safety. Among 15 patients with MCL with a median disease duration of 5·1 years and a median of four prior treatments, the ORR was 53%. Three patients (20%) had a complete response and 5 (33%) had a partial response. The median duration of response was 13·7 months and median PFS was 5·6 months. Four of five patients who relapsed after transplantation and two of five patients who previously received bortezomib responded to lenalidomide. The most common grade 4 adverse event was thrombocytopenia (13%) and the most common grade 3 adverse events were neutropenia (40%), leucopenia (27%) and thrombocytopenia (20%). In conclusion, oral lenalidomide monotherapy is well tolerated and active in relapsed or refractory MCL.

Successful therapy with methotrexate of a multicentric mixed lymphoma of the central nervous system.

Primary lymphoma of the central nervous system (CNS) is extremely rare. A case of mixed histiocytic lymphocytic lymphoma of the CNS that initially occurred in the spinal cord is reported. Multicentric recurrence following radiotherapy was successfully treated with intrathecal methotrexate and the patient remains free of disease after 4 years. The role of intrathecal methotrexate as alternative therapy following irradiation failure is discussed.