First Report of a Phase II Clinical Trial of Lenalidomide Oral Therapy for Peripheral T-Cell Lymphoma.

BACKGROUND: Lenalidomide has immunomodulatory and anti-neoplastic properties, with demonstrated activity in myelodysplastic syndrome and multiple myeloma. Preliminary reports indicate that lenalidomide has activity against cutaneous T-cell lymphoma (mycosis fungoides) and chronic lymphocytic leukemia. We hypothesized that lenalidomide should be studied as a non chemotherapy approach for Peripheral T- Cell Lymphoma (PTCL).

STUDY DESIGN AND METHODS: In this Canadian multi-center, open label, single-arm, phase II clinical trial, patients with PTCL were treated with lenalidomide 25 mg po qd × 21 days on a 28-day cycle until disease progression, death or unacceptable toxicity. Patients with ECOG 0-2 and relapsed/refractory disease were eligible, as well as patients who had not previously had systemic therapy but who were ineligible for standard curative chemotherapy regimens due to comorbid illness. We report on the first ten patients enrolled. The primary endpoint is response rate defined according to the 1999 Cheson criteria.

RESULTS: Median age of participants was 56y (range, 42–76y), 9M, 1F. Histologies included PTCL not otherwise specified (n=4), angioimmunoblastic (n=4), cutaneous anaplastic large cell (n=1), hepatosplenic gamma/delta (n=1). 8 were relapsed, 2 previously untreated. 2 were refractory to their previous regimen. Median number of prior lines of systemic therapy is 1 (range, 0–3). Median number of cycles delivered to date, 2 (range: 1–8). Therapy has generally been well tolerated. 3 patients experienced grade 3–4 hematological toxicity, 3 experienced grade 3+ infectious complications and 1 had grade 3 rash. No thrombotic events have been seen to date. Best responses to date include 0 CR, 4 PR (2 angioimmunoblastic, 2 PTCL NOS), 1 SD (PTCL NOS), 2 PD (1 angioimmunoblastic, 1 PTCL NOS). Three deaths have occurred on study, due to disease progression (n=2) and pneumonia during cycle 1 (n=1, angioimmunoblastic). One patient has withdrawn from study post cycle 1 due to treatment related asthenia. One previously untreated patient still awaits the first response assessment; the overall response rate (CR+PR) to date in the remaining patients on an intent-to-treat basis is 4/9 (44%). 5 of 9 (56%) patients have achieved stable disease or better, for 2+, 3+, 5, 6 and 8+ months. For the two patients with previously refractory disease, best response was 1 PR for 6 months and 1 PD.

CONCLUSION: Lenalidomide appears to be an active agent in the treatment of relapsed PTCL with an acceptable tolerability profile. Further recruitment and follow-up will allow us to better define the response rate, tolerability, TTP and OS with this regimen.