A phase I/II trial of brentuximab vedotin plus rituximab as frontline therapy for patients with immunosuppression-associated CD30+ and/or EBV + lymphomas

Abstract

Treatment strategies for post-transplant lymphoproliferative disorders (PTLD) consist of response-adapted risk-stratified methods using immunosuppression reduction, immunotherapy, and chemotherapy. We investigated the efficacy of Brentuximab vedotin given concurrently with Rituximab (BV + R) once weekly for four weeks, followed by optional consolidation, and up to one year of maintenance. Among 20 assessable patients, BV + R therapy resulted in an overall response rate of 75% (95% CI 51 to 91, p = 0.044) with 60% achieving a complete response. Median time to best response was 28 days. Two-year progression-free survival and overall survival rates were 75 and 90%, respectively. Most common severe grade 3/4 treatment-related toxicities included neutropenia (40%), hypertension (30%), infection (25%), and peripheral neuropathy (15%). BV + R is a novel and effective therapeutic strategy that achieved rapid and durable remissions in previously untreated PTLD patients; however, this treatment platform requires further modification due to the high rates of treatment-related toxicity.

Key points

• Brentuximab vedotin + Rituximab showed ORR and CR rates of 75 and 60% in patients with immunosuppression-associated lymphoid malignancies

• High rates of treatment delay were attributed to treatment-related toxicity; further dosing optimization of this regimen is required

Keywords:

• Chemotherapeutic approaches
• lymphoma and Hodgkin disease
• antibody-based immunotherapy

Acknowledgments

We also wish to thank the patients and staff members at all study centers who participated in this research.

Disclosure statement

No potential conflict of interest was reported by the author(s). BP: Honoraria - Takeda, Seattle Genetics; JNW; RK: Speaker’s bureau – Kite/Gilead, BMS/Celgene/Juno, AstraZeneca, BeiGene; Advistory board – Karyopharm, BMS/Celegene/Juno, Kite/Gilead; AME: Advisory board (Research Related): Seattle Genetics, MorphoSys, Mylteni, Epizyme; Consultant (Educational Related): Research to Practice, Physician Education Resource, Cota, OncLive; Consultant (Data and Safety Monitoring Board): Novartis, Pharmacyclics; AK: Lectureship and Honoraria – Pfizer, Foundation Medicine, Bayer.

Additional information

Funding

The authors of this study would like to acknowledge Seattle Genetics and HHS Holdings as the primary funders of this study. BP: Research support – Merck. RK: Research support – Kite/Gilead, BMS/Celgene/Juno, Takeda