PMID- 36534160
OWN - NLM
STAT- MEDLINE
DCOM- 20230403
LR  - 20230421
IS  - 2473-9537 (Electronic)
IS  - 2473-9529 (Print)
IS  - 2473-9529 (Linking)
VI  - 7
IP  - 7
DP  - 2023 Apr 11
TI  - Safety and efficacy of letetresgene autoleucel alone or with pembrolizumab for 
      relapsed/refractory multiple myeloma.
PG  - 1168-1177
LID - 10.1182/bloodadvances.2022008460 [doi]
AB  - This pilot study assessed the safety and efficacy of letetresgene autoleucel 
      (lete-cel; GSK3377794), a genetically modified autologous T-cell therapy 
      targeting New York esophageal squamous cell carcinoma-1 (NY-ESO-1)/L antigen 
      family member 1 isoform A (LAGE-1a)-positive myeloma cells, alone or in 
      combination with pembrolizumab in patients with relapsed/refractory multiple 
      myeloma. Eligible patients expressed NY-ESO-1 and/or LAGE-1a and either 
      HLA-A *02:01,  *02:05, or  *02:06. Patients received lete-cel single infusion alone 
      (arm 1) or with pembrolizumab (arm 2). 127 patients were screened, and 6 patients 
      (3 per arm) were enrolled; patients in arm 1 and 2 received lete-cel alone, or 
      with pembrolizumab, respectively. All patients exhibited grade 3/4 cytopenias, 
      which resolved or improved to grade 1. One patient (arm 1) had grade 3/4 
      lete-cel-related adverse events (AEs); 2 patients (arm 2) had grade 3/4 AEs 
      related to lete-cel and lymphodepletion. Three patients with grade 1/2 cytokine 
      release syndrome (CRS) exhibited elevated post-lete-cel interleukin-6 levels 
      versus those without CRS. Pooled overall response rate was 50% including 1 
      patient each with confirmed clinical response, very good clinical response, and 
      partial response, and progression-free survival ranged from 1.3 to 5.2 months. 
      Responders (arm 1: n = 1; arm 2: n = 2) had a time-to-response of 3 weeks, 
      duration of response of 2.1 months. Two responders, but no nonresponders, 
      exhibited elevated cytokine levels after lete-cel infusion. Lete-cel had a 
      manageable safety profile and demonstrated clear but transient antitumor activity 
      in patients with relapsed/refractory multiple myeloma. This trial was registered 
      at www.clinicaltrials.gov as #NCT03168438.
CI  - (c) 2023 by The American Society of Hematology. Licensed under Creative Commons 
      Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), 
      permitting only noncommercial, nonderivative use with attribution. All other 
      rights reserved.
FAU - Nishihori, Taiga
AU  - Nishihori T
AUID- ORCID: 0000-0002-2621-7924
AD  - Moffitt Cancer Center, Tampa, FL.
FAU - Hoffman, James E
AU  - Hoffman JE
AD  - Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, 
      FL.
FAU - Huff, Anne
AU  - Huff A
AD  - GlaxoSmithKline, Collegeville, PA.
FAU - Kapoor, Gurpreet S
AU  - Kapoor GS
AD  - GlaxoSmithKline, Collegeville, PA.
FAU - Eleftheriadou, Ioanna
AU  - Eleftheriadou I
AUID- ORCID: 0000-0002-0278-1061
AD  - GlaxoSmithKline, Collegeville, PA.
FAU - Zajic, Stefan
AU  - Zajic S
AUID- ORCID: 0000-0002-9844-9951
AD  - GlaxoSmithKline, Collegeville, PA.
FAU - Urbano, Alisa
AU  - Urbano A
AD  - GlaxoSmithKline, Collegeville, PA.
FAU - Suchindran, Sunil
AU  - Suchindran S
AD  - GlaxoSmithKline, Collegeville, PA.
FAU - Chisamore, Michael
AU  - Chisamore M
AD  - Merck & Co, Inc, Rahway, NJ.
FAU - D'Souza, Jimson W
AU  - D'Souza JW
AD  - GlaxoSmithKline, Collegeville, PA.
FAU - Faitg, Thomas
AU  - Faitg T
AD  - GlaxoSmithKline, Collegeville, PA.
FAU - Rapoport, Aaron P
AU  - Rapoport AP
AD  - University of Maryland Greenebaum Comprehensive Cancer Center and School of 
      Medicine, Baltimore, MD.
LA  - eng
SI  - ClinicalTrials.gov/NCT03168438
GR  - P30 CA134274/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Blood Adv
JT  - Blood advances
JID - 101698425
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Humans
MH  - *Multiple Myeloma/drug therapy/genetics
MH  - *Esophageal Neoplasms
MH  - Pilot Projects
MH  - *Esophageal Squamous Cell Carcinoma
PMC - PMC10111356
COIS- Conflict-of-interest disclosure: T.N. receives/has received research funding from 
      Novartis and Karyopharm and is a member of the advisory committee for Medexas but 
      has declined to receive compensation. A.H., G.S.K., I.K., S.Z., J.W.D., W.D., 
      T.F., A.U., and S.S. are employees of and/or hold stocks/shares in GSK. M.C. is 
      an employee of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co, Inc, Rahway, 
      NJ, US, and holds stocks/shares in Merck & Co, Inc, Rahway, NJ, US. A.P.R. 
      declares no conflicts of interest other than support received as site principal 
      investigator for this study. The remaining author declares no competing financial 
      interests.
EDAT- 2022/12/20 06:00
MHDA- 2023/04/03 06:42
PMCR- 2022/12/20
CRDT- 2022/12/19 11:14
PHST- 2022/11/08 00:00 [accepted]
PHST- 2022/07/08 00:00 [received]
PHST- 2023/04/03 06:42 [medline]
PHST- 2022/12/20 06:00 [pubmed]
PHST- 2022/12/19 11:14 [entrez]
PHST- 2022/12/20 00:00 [pmc-release]
AID - 493750 [pii]
AID - 10.1182/bloodadvances.2022008460 [doi]
PST - ppublish
SO  - Blood Adv. 2023 Apr 11;7(7):1168-1177. doi: 10.1182/bloodadvances.2022008460.