PMID- 37339586 OWN - NLM STAT- MEDLINE DCOM- 20240325 LR - 20240325 IS - 1528-0020 (Electronic) IS - 0006-4971 (Linking) VI - 142 IP - 16 DP - 2023 Oct 19 TI - Pembrolizumab plus vorinostat induces responses in patients with Hodgkin lymphoma refractory to prior PD-1 blockade. PG - 1359-1370 LID - 10.1182/blood.2023020485 [doi] AB - 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. CI - (c) 2023 by The American Society of Hematology. FAU - Mei, Matthew AU - Mei M AUID- ORCID: 0000-0002-1109-6955 AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Chen, Lu AU - Chen L AD - Division of Biostatistics, City of Hope, Duarte, CA. FAU - Godfrey, James AU - Godfrey J AUID- ORCID: 0000-0002-4103-4288 AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Song, Joo AU - Song J AD - Department of Pathology, City of Hope, Duarte, CA. FAU - Egelston, Colt AU - Egelston C AUID- ORCID: 0000-0001-8440-1271 AD - Department of Immuno-Oncology, City of Hope, Duarte, CA. FAU - Puverel, Sandrine AU - Puverel S AUID- ORCID: 0000-0002-8667-5193 AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Budde, L Elizabeth AU - Budde LE AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Armenian, Saro AU - Armenian S AUID- ORCID: 0000-0003-2604-8603 AD - Department of Pediatrics, City of Hope, Duarte, CA. FAU - Nikolaenko, Liana AU - Nikolaenko L AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Nwangwu, Mary AU - Nwangwu M AD - Department of Immuno-Oncology, City of Hope, Duarte, CA. FAU - Guo, Weihua AU - Guo W AUID- ORCID: 0000-0002-9580-513X AD - Department of Immuno-Oncology, City of Hope, Duarte, CA. FAU - Gao, Lei AU - Gao L AD - Toni Stephenson Lymphoma Center, City of Hope, Duarte, CA. FAU - Lee, Peter AU - Lee P AD - Department of Immuno-Oncology, City of Hope, Duarte, CA. FAU - Chen, Robert AU - Chen R AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Daniels, Shari AU - Daniels S AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Kennedy, Neena AU - Kennedy N AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Peters, Lacolle AU - Peters L AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Zain, Jasmine AU - Zain J AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Rosen, Steven AU - Rosen S AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Forman, Stephen AU - Forman S AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Popplewell, Leslie AU - Popplewell L AUID- ORCID: 0000-0002-8418-2811 AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Kwak, Larry AU - Kwak L AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. FAU - Herrera, Alex F AU - Herrera AF AUID- ORCID: 0000-0002-9665-7415 AD - Division of Lymphoma, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA. LA - eng SI - ClinicalTrials.gov/NCT03150329 PT - Journal Article PL - United States TA - Blood JT - Blood JID - 7603509 RN - DPT0O3T46P (pembrolizumab) RN - 58IFB293JI (Vorinostat) RN - 0 (Programmed Cell Death 1 Receptor) RN - 0 (Antibodies, Monoclonal, Humanized) SB - IM CIN - Blood. 2023 Oct 19;142(16):1333-1334. PMID: 37856096 MH - Adult MH - Humans MH - *Hodgkin Disease/drug therapy MH - Vorinostat MH - Programmed Cell Death 1 Receptor/therapeutic use MH - Neoplasm Recurrence, Local MH - *Antibodies, Monoclonal, Humanized EDAT- 2023/06/21 01:07 MHDA- 2024/03/25 06:42 CRDT- 2023/06/20 18:12 PHST- 2023/05/18 00:00 [accepted] PHST- 2023/03/20 00:00 [received] PHST- 2024/03/25 06:42 [medline] PHST- 2023/06/21 01:07 [pubmed] PHST- 2023/06/20 18:12 [entrez] AID - S0006-4971(23)01463-5 [pii] AID - 10.1182/blood.2023020485 [doi] PST - ppublish SO - Blood. 2023 Oct 19;142(16):1359-1370. doi: 10.1182/blood.2023020485.