Multicenter phase 2 study of romidepsin plus lenalidomide for previously untreated peripheral T-cell lymphoma.

PTCL are aggressive malignancies associated with poor prognosis when treated with cytotoxic chemotherapy. We report the findings of a phase 2 study evaluating a chemotherapy-free combination of romidepsin plus lenalidomide as initial treatment for PTCL patients who were over 60 years of age or noncandidates for standard induction chemotherapy (ClinicalTrials.gov-NCT02232516). Treatment was initiated with romidepsin 10 mg/m2 IV on d 1, 8, 15, and lenalidomide 25 mg PO on d 1-21 of 28-day cycle for up to 1 year. The primary objective was ORR. Secondary objectives included safety and survival. The study enrolled 29 patients with a median age of 75 at 3 US centers, including 16 (55%) AITL, 10 (34%) PTCL-NOS, 2 ATLL and 1 EATCL. Grade 3-4 hematologic toxicities included neutropenia (45%), thrombocytopenia (34%) and anemia (28%). Grade 3-4 non-hematologic toxicities included hyponatremia (45%), hypertension (38%), hypoalbuminemia (24%), fatigue (17%), hyperglycemia (14%), hypokalemia (14%), dehydration (10%), and infection (10%). At a median follow-up of 15.7 months, 23 subjects were evaluable and received a median treatment of 6 cycles. The ORR was 65.2% with CR at 26.1%, including ORR 78.6% and CR 35.7% for AITL. Median DOR was 10.7 months, and 27.1 months for patients achieving CR. The estimated 1-yr PFS was 48.6% with 2-yr PFS at 31.5%, and the estimated 1-yr OS was 71.1% with 2-yr OS at 49.5%. This study provides the first demonstration that the chemotherapy-free biologic combination of romidepsin and lenalidomide is feasible and effective as initial therapy for PTCL and warrants further evaluation.