Final Results of a Phase II Study of Brentuximab Vedotin and Lenalidomide in Relapsed and Refractory T-Cell Lymphomas

Brentuximab vedotin (BV) and lenalidomide (Len) demonstrate independent activity in peripheral T cell lymphoma (PTCL) and cutaneous T cell lymphoma (CTCL). This study evaluated the efficacy and safety of this combination at reduced doses.

This phase II trial enrolled 26 patients (table 1) with relapsed/refractory PTCL/CTCL. CD30 positivity was not required, and prior BV treatment was not exclusionary. Patients were treated with BV 1.2 mg/kg IV q3weeks and Len 20 mg PO daily. Len was reduced to 10 mg due to tolerability. The primary endpoint was overall response rate (ORR).

Enrolled patients had a median age of 60 (37-90), 18 were male (69%), and had a median of 4.5 prior lines of therapy (1-9). Thirteen patients (50%) were diagnosed with mycosis fungoides, 8 with PTCL (31%), 3 with Sezary syndrome (12%), and 2 with CD30+ lymphoproliferative disorder (8%). The mean CD30 percent positivity was 7.5% (1-75%); CD30 was negative in 4 patients (18%).

Five patients achieved complete response (2 CTCL, 3 PTCL), four achieved partial response (3 CTCL, 1 PTCL), and ten had stable disease (all CTCL). The ORR was 27.8% (5/18) for CTCL and 50% (4/8) for PTCL. Nineteen patients experienced grade 3 or higher adverse events, the most common of which were neutropenia (19.2%), lymphopenia, rash, fatigue, and abdominal pain (11.5% each) Patients came off treatment most commonly for progression (54%) and adverse events (23%).

This combination demonstrated efficacy that was comparable to each agent when used as monotherapy. After reducing the Len dose to 10 mg, the combination had toxicity similar when compared to monotherapy at FDA approved dosing, although hematologic toxicity may be slightly higher. Including patients who were CD30 negative (4 patients, 18%) and having a relatively low median CD30 positivity at 7.5% may explain the lack of substantial improvement in efficacy over monotherapy with either agent. The trial was terminated early because of poor accrual.