PMID- 36913694
OWN - NLM
STAT- MEDLINE
DCOM- 20230531
LR  - 20240324
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 141
IP  - 21
DP  - 2023 May 25
TI  - Concurrent pembrolizumab with AVD for untreated classic Hodgkin lymphoma.
PG  - 2576-2586
LID - 10.1182/blood.2022019254 [doi]
AB  - Concurrent administration of pembrolizumab with chemotherapy in untreated classic 
      Hodgkin lymphoma (CHL) has not been studied previously. To investigate this 
      combination, we conducted a single-arm study of concurrent pembrolizumab with AVD 
      (doxorubicin, vinblastine, and dacarbazine; APVD) for untreated CHL. We enrolled 
      30 patients and met the primary safety end point with no observed significant 
      treatment delays in the first 2 cycles. Twelve patients experienced grade 3 or 4 
      nonhematologic adverse events (AEs), most commonly febrile neutropenia and 
      infection/sepsis. Grade 3 or 4 immune-related AEs, including alanine 
      aminotransferase elevation and aspartate aminotransferase elevation were observed 
      in 3 patients. One patient experienced an episode of grade 2 colitis and 
      arthritis. Six patients missed at least 1 dose of pembrolizumab because of AEs, 
      primarily grade 2 or higher transaminitis. Among 29 response-evaluable patients, 
      the best overall response rate was 100% and the complete response rate was 90%. 
      With a median follow-up of 2.1 years, the 2-year progression-free survival (PFS) 
      and overall survival were 97% and 100%, respectively. To date, no patient who has 
      withheld or discontinued pembrolizumab because of toxicity has progressed. 
      Clearance of circulating tumor DNA (ctDNA) was associated with superior PFS when 
      measured after cycle 2 and at the end of treatment (EOT). None of the 4 patients 
      with persistent uptake by fluorodeoxyglucose positron emission tomography (PET) 
      at EOT yet negative ctDNA have relapsed to date. Concurrent APVD shows promising 
      safety and efficacy but may yield spurious PET findings in some patients. This 
      trial was registered at www.clinicaltrials.gov as #NCT03331341.
FAU - Lynch, Ryan C
AU  - Lynch RC
AUID- ORCID: 0000-0001-6703-0894
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
AD  - Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA.
FAU - Ujjani, Chaitra S
AU  - Ujjani CS
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
AD  - Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA.
FAU - Poh, Christina
AU  - Poh C
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Warren, Edus H
AU  - Warren EH
AUID- ORCID: 0000-0002-9570-2755
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
AD  - Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA.
FAU - Smith, Stephen D
AU  - Smith SD
AUID- ORCID: 0000-0001-5354-7593
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
AD  - Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA.
FAU - Shadman, Mazyar
AU  - Shadman M
AUID- ORCID: 0000-0002-3365-6562
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
AD  - Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA.
FAU - Till, Brian
AU  - Till B
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
AD  - Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA.
FAU - Raghunathan, Vikram M
AU  - Raghunathan VM
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Alig, Stefan
AU  - Alig S
AD  - Division of Oncology, Stanford University, Stanford, CA.
FAU - Alizadeh, Ash A
AU  - Alizadeh AA
AUID- ORCID: 0000-0002-5153-5625
AD  - Division of Oncology, Stanford University, Stanford, CA.
FAU - Gulhane, Avanti
AU  - Gulhane A
AUID- ORCID: 0000-0002-5264-951X
AD  - Department of Radiology, University of Washington, Seattle, WA.
FAU - Chen, Delphine L
AU  - Chen DL
AUID- ORCID: 0000-0002-0150-5401
AD  - Department of Radiology, University of Washington, Seattle, WA.
FAU - Tseng, Yolanda
AU  - Tseng Y
AD  - Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA.
AD  - Department of Radiation Oncology, University of Washington, Seattle, WA.
FAU - Coye, Hilary
AU  - Coye H
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Shelby, Megan
AU  - Shelby M
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Ottemiller, Susan
AU  - Ottemiller S
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Keo, Sarith
AU  - Keo S
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Verni, Kaitlin
AU  - Verni K
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Du, Hongyan
AU  - Du H
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Vandermeer, Jacquelin
AU  - Vandermeer J
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Gaston, Ashley
AU  - Gaston A
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Rasmussen, Heather
AU  - Rasmussen H
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Martin, Paul
AU  - Martin P
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Marzbani, Edmond
AU  - Marzbani E
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
FAU - Voutsinas, Jenna
AU  - Voutsinas J
AD  - Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA.
FAU - Gopal, Ajay K
AU  - Gopal AK
AD  - Division of Medical Oncology, University of Washington, Seattle, WA.
AD  - Clinical Research Division, Fred Hutch Cancer Center, Seattle, WA.
LA  - eng
SI  - ClinicalTrials.gov/NCT03331341
GR  - R01 CA229766/CA/NCI NIH HHS/United States
GR  - R01 CA233975/CA/NCI NIH HHS/United States
GR  - R01 CA257655/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 7XL5ISS668 (Brentuximab Vedotin)
RN  - 80168379AG (Doxorubicin)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
CIN - Blood. 2023 May 25;141(21):2545-2546. PMID: 37227795
MH  - Humans
MH  - Antibodies, Monoclonal, Humanized/adverse effects
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - Brentuximab Vedotin
MH  - Doxorubicin/adverse effects
MH  - *Hodgkin Disease/pathology
PMC - PMC10273164
COIS- Conflict-of-interest disclosure: R.C.L. reports research funding from TG 
      Therapeutics, Incyte, Bayer, Cyteir, Genentech, Seagen, and Rapt and consultancy 
      at Cancer Study Group and Seagen. C.S.U. reports consultancy at Genentech. S.D.S. 
      reports research funding from ADC Therapeutics, AstraZeneca, Ayala (spouse), 
      Bayer, BeiGene, Bristol Myers Squibb (BMS; spouse), De Novo Biopharma, Enterome, 
      Genentech, Ignyta (spouse), Incyte Corporation, Kymera Therapeutics, Merck Sharp 
      and Dohme Corp, MorphoSys, Nanjing Pharmaceuticals Co, Ltd, Portola 
      Pharmaceuticals, and Viracta Therapeutics and consultancy or membership on 
      advisory board at ADC Therapeutics, AstraZeneca, BeiGene, Epizyme, Karyopharm, 
      KITE pharma, Incyte, Numab Therapeutics AG, AbbVie, and Coherus Biosciences. B.T. 
      reports consultancy at Mustang Bio and Proteios Technology; patents and royalties 
      at Mustang Bio; and research funding from Mustang Bio and BMS/Celgene. M. Shadman 
      reports consulting, being on advisory boards, steering committees, or data safety 
      monitoring committees at AbbVie, Genentech, AstraZeneca, Sound Biologics, 
      Pharmacyclics, Beigene, BMS, Morphosys/Incyte, TG Therapeutics, Innate Pharma, 
      Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune, Mustang 
      Bio, Regeneron, Merck, Fate Therapeutics, MEI pharma, and Atara Biotherapeutic 
      and research funding from Mustang Bio, Celgene, BMS, Pharmacyclics, Gilead, 
      Genentech, AbbVie, TG Therapeutics, BeiGene, AstraZeneca, Sunesis, Atara 
      Biotherapeutics, Genmab, MorphoSys/Incyte, and Vincerx. A.A.A. reports ownership 
      interest in CiberMed, Forty Seven Inc, and Foresight Diagnostics; patent filings 
      related to cancer biomarkers; research funding from BMS and Celgene; and paid 
      consultancies from Genentech, Karyopharm, Roche, Chugai, Gilead, and Celgene. 
      A.G. reports research funding from Merck, I-Mab Biopharma, IgM Bio, Takeda, 
      Gilead, AstraZeneca, Agios, Janssen, BMS, Seagen, Teva, and Genmab; 
      consultancy/honoraria from Incyte, Kite, Morphosys/Incyte, ADC Therapeutics, 
      Acrotech, Merck, Karyopharm, Servier, BeiGene, Cellectar, Janssen, Seagen, 
      Epizyme, I-Mab Biopharma, Gilead, Genentech, Lilly, Caribou, and Fresenius-Kabi; 
      and equity ownership at Compliment Corporation. The remaining authors declare no 
      competing financial interests.
EDAT- 2023/03/14 06:00
MHDA- 2023/05/29 06:42
PMCR- 2024/05/25
CRDT- 2023/03/13 17:09
PHST- 2023/02/27 00:00 [accepted]
PHST- 2022/12/05 00:00 [received]
PHST- 2024/05/25 00:00 [pmc-release]
PHST- 2023/05/29 06:42 [medline]
PHST- 2023/03/14 06:00 [pubmed]
PHST- 2023/03/13 17:09 [entrez]
AID - S0006-4971(23)00667-5 [pii]
AID - 10.1182/blood.2022019254 [doi]
PST - ppublish
SO  - Blood. 2023 May 25;141(21):2576-2586. doi: 10.1182/blood.2022019254.