Final Report Of a Phase II Clinical Trial Of Lenalidomide Monotherapy For T-Cell Lymphoma
Authors: Toumishey Ethan , Prasad Angeli , Dueck Gregory S. , Chua Neil , Finch Daygen , Stewart Douglas A. , White Darrell J. , van der Jagt Richard H. , Johnston James B , Belch Andrew R , Reiman Tony 
Published: October 2019

Abstract

Background
Patients with T-cell lymphomas face a poorer prognosis when compared to patients with B-cell lymphomas. New therapeutic approaches need to be developed in order to improve outcomes for these patients. We report the final results of a phase 2 multicenter clinical trial evaluating lenalidomide monotherapy in T-cell lymphomas.

Methods
Forty patients with relapsed and refractory T-cell lymphomas other than mycosis fungoides, as well as patients with untreated T-cell lymphoma who were not candidates for combination chemotherapy, were prescribed oral lenalidomide (25mg daily) on days 1 to 21 of each 28 day cycle, with standardized dose reductions for toxicity. Treatment continued until disease progression, death or unacceptable toxicity. The primary endpoint was overall response rate, and secondary endpoints were complete and partial response rates, progression-free and overall survival (PFS, OS), and safety. We also determined duration of response (DoR).

Results
Forty patients were enrolled in the study; one was subsequently deemed ineligible. In the 39 eligible patients, the median age was 65. ECOG PS was 0-1 (n=29), 2 (n=8), and 3 (n=2). The histology of the studied cases included peripheral T-cell unspecified (PTCL-u, n=14), angioimmunoblastic (n=9), anaplastic large cell (n=10), enteropathic T-cell (n=2), Hepatosplenic gamma/delta (n=2), and lymphoblastic T-cell lymphoma (n=2). The number of prior therapies was 0 (n=8), 1 (n=14), 2 (n=8), 3 (n=6), 4 (n=2), and 5 (n=1). Five patients had previous autologous stem cell transplant. Eleven patients were refractory to their previous treatment. The median time from diagnosis until the start of treatment was 14 months (range, 1-204 months). The median time from completion of prior therapy to the start of lenalidomide was 5 months (range, 1-48 months). The ORR was 10/39 (26%); 3 (8%) were complete responses and 7 were partial responses. Responses occurred in anaplastic, angioimmunoblastic, and PTCL-u histologies. Three additional patients had SD ≥5 cycles. The median OS was 12 months (range<1-69+ months), median PFS was 4 months (range,<1-50+ months) and the median DoR was 13 months (range 2-37+ months), including 5 responses lasting greater than 1 year. The most common grade 4 adverse event was thrombocytopenia (21%) while pain NOS (21%) and neutropenia (13%) were the most commonly reported grade 3 adverse events. Among the patients who had relapsed/refractory peripheral T-cell lymphoma (n=29) the ORR was 24%, median OS was 12 months, median PFS was 4 months, and median DoR was 5 months (range, 2-37+ months). The ORR of the subpopulation of previously untreated patients who were not eligible for combined chemotherapy (n=8) was 43%, median OS was 22 months (range,<1-38+ months), median PFS was 2 months (range,<1-38+ months), and median DoR was 21 months (range 5-28+ months).

Discussion
In T-cell lymphomas, oral lenalidomide monotherapy demonstrated clinically relevant efficacy. The toxicity profile in T-cell lymphoma is manageable and consistent with prior studies involving lenalidomide. Lenalidomide also showed promise for patients who are not eligible for combination chemotherapy. The results with lenalidomide in relapsed/refractory patients are comparable to those seen with other available monotherapies for this disease. Several durable (>1 year) responses were seen, but the proportion of durable responses was low. Future development of lenalidomide therapy for T-cell lymphomas should include efforts to identify the subset of patients most likely to benefit, and the development of rational drug combinations.

Disclosures:
Off Label Use: Lenalidomide was prescribed to treat T-cell lymphoma. Stewart:Celgene: Honoraria. van der Jagt:Millenium: Consultancy; Roche: Consultancy; Celgene: Consultancy. Reiman:Celgene: Consultancy; Celgene: Research Funding.