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

Abstract

Peripheral T-cell lymphomas (PTCLs) are 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 patients with PTCL who were aged >60 years or noncandidates for chemotherapy. Treatment was initiated with romidepsin 10 mg/m2 IV on days 1, 8, and 15 and lenalidomide 25 mg taken orally from days 1 to 21 of 28-day cycle for up to 1 year. The primary objective was overall response rate (ORR). Secondary objectives included safety and survival. The study enrolled 29 patients with a median age of 75 years, including 16 (55%) angioimmunoblastic T-cell lymphoma (AITL), 10 (34%) PTCL- not otherwise specified, 2 ATLL, and 1 EATL. Grade 3 to 4 hematologic toxicities included neutropenia (45%), thrombocytopenia (34%), and anemia (28%). Grade 3 to 4 nonhematologic toxicities included hyponatremia (45%), hypertension (38%), hypoalbuminemia (24%), fatigue (17%), hyperglycemia (14%), hypokalemia (14%), dehydration (10%), and infection (10%). At median follow-up of 15.7 months, 23 patients were evaluable and received a median treatment of 6 cycles. The ORR was 65.2% with complete response (CR) at 26.1%, including 78.6% ORR and 35.7% CR for AITL. Median duration of response was 10.7 months, with 27.1 months for patients achieving CR. The estimated 2-year progression-free survival was 31.5%, and 2-year overall survival was 49.5%. This study provides the first demonstration that the biologic combination of romidepsin and lenalidomide is feasible and effective as initial therapy for PTCL and warrants further evaluation. This trial was registered at www.clinicaltrials.gov as #NCT02232516.

Graphical abstract

Figure 1.

Study treatment schema and patient disposition flowchart. (A) The study treatment schema. Treatment consisted of romidepsin 10 mg/m² (with dose escalation to 14 mg/m² as tolerated) IV on days 1, 8, and 15 and lenalidomide 25 mg taken orally from days 1 to 21 of 28-day cycle for up to 1 year. (B) The flowchart for patient disposition. Of the 29 patients enrolled, 20 completed at least 3 cycles of study treatment and were evaluable. Fifteen participants achieved responses.

Figure 2.

Kaplan-Meier survival curves. PFS for all patients (A) and AITL subset (B). OS for all patients (C) and AITL subset (D).

Figure 3.

Swimmer plot of time on study and duration of responses. Solid bar length indicates time on study, with red solid bar denoting CR, orange denoting partial response, purple denoting stable disease, and blue denoting progression of disease. Blue shaded bar denotes response duration after study treatment discontinuation. Green diamond denotes stem cell transplant, yellow cross denotes subsequent cytotoxic chemotherapy, green asterisk denotes time to best response, black cross denotes disease progression, gray circle denotes study withdrawal or lost to follow-up, and black diamond denotes death. “//” stands for axis break, which denotes noncontinuous timeline.