Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade

Matthew Mei, Lu Chen, James Godfrey, Joo Song, Colt Egelston, Sandrine Puverel, L. Elizabeth Budde, Saro Armenian, Liana Nikolaenko, Mary Nwangwu, Weihua Guo, Lei Gao, Peter Lee, Robert Chen, Shari Daniels, Neena Kennedy, Lacolle Peters, Jasmine Zain, Steven Rosen, Stephen FormanLeslie Popplewell, Larry Kwak, Alex F. Herrera

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

This phase 1 study evaluated the addition of vorinostat to pembrolizumab in patients with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL), diffuse large B-cell lymphoma, and follicular lymphoma. We report the results in cases of cHL. Adult patients with RR cHL who had received ≥1 prior lines of therapy and were ineligible for transplantation were treated in a dose-escalation cohort with 2 dose levels (DLs) and then on an expansion cohort at the recommended phase 2 dose (RP2D) in 21-day cycles. Vorinostat 100 mg twice a day (DL1) and 200 mg twice a day (DL2) was administered orally from days 1 to 5 and 8 to 12; all patients received pembrolizumab 200 mg IV every 3 weeks. The primary end point was safety and determination of RP2D. In total, 32 patients with cHL were enrolled, including 30 at DL2 (RP2D); 78% had received prior anti–programmed cell death 1 (anti–PD-1) therapy, and 56% were PD-1 refractory. Grade ≥3 adverse events (AEs) included hypertension (9%), neutropenia (9%), hypophosphatemia (9%), thrombocytopenia (6%), and lymphopenia (6%). Immune-related AEs included grade 1 or 2 thyroiditis (13%), grade 1 rash (6%), and grade 3 esophagitis/duodenitis (3%). The overall response rate (ORR) was 72% and complete response (CR) rate was 34%. Patients refractory to prior PD-1 blockade (n = 18) had ORR and CR rates of 56% and 11%, respectively. Pembrolizumab and vorinostat was well tolerated with a high ORR rate in RR cHL including in anti–PD-1–refractory disease. This trial was registered at www.clinicaltrials.gov as #NCT03150329.

Original languageEnglish (US)
Pages (from-to)1359-1370
Number of pages12
JournalBlood
Volume142
Issue number16
DOIs
StatePublished - Oct 19 2023

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade'. Together they form a unique fingerprint.

Cite this