Brentuximab vedotin addition to gemcitabine in relapsed or refractory peripheral T-cell lymphoma: a LYSA phase 2 study.

We aim to evaluate the efficacy of brentuximab vedotin (BV) combined with gemcitabine (GBV) followed by BV maintenance in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL). Patients with at least 5% CD30+ cells by immunohistochemistry received 4 GBV induction (28 days) cycles of gemcitabine 1000 mg/m2 (day 1, day 15) plus BV 1.8 mg/kg (day 8) followed, in responding patients, by up to 12 BV maintenance (21 day) cycles. Primary end point was overall response rate (ORR) after 4 induction cycles by computed tomography scan-based Lugano criteria. Of 71 enrolled patients (median age of 66 years), 80.3% had received 1 previous line and 60.6% were refractory. The diagnoses per pathology central review were follicular helper T-cell lymphomas (TFHL; 47.9%), anaplastic large-cell lymphomas (ALCL; anaplastic lymphoma kinase [ALK] negative [19.7%] and ALK+ [7%]), peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS; 12.7%), and other entities (12.7%). In the intention-to-treat analysis, ORR was 46.5%, with 19.7% complete response. Twenty-eight patients received maintenance. Grade 3 to 4 adverse events reported in ≥10% of patients during induction comprised neutropenia (55%), thrombocytopenia (14%), anemia (21%), and infection (14%); during maintenance comprised neutropenia (39%), thrombocytopenia (21%), and peripheral neuropathy (14%). With a median follow-up of 32.6 months, the median duration of response, progression-free, and overall survival were 15.8, 4.5, and 12.9 months, respectively. Efficacy, higher in ALCL, was present in the TFHL and PTCL-NOS group. A negative association of high baseline soluble CD30 on both response and survival was found, which, in ad hoc analysis, appeared highly relevant in patients with TFHL and PTCL-NOS. This trial was registered at the European Union Drug Regulating Authorities Clinical Trials database as #2017-000409-1, and at www.clinicaltrials.gov as #NCT03496779.