Omidubicel vs standard myeloablative umbilical cord blood transplantation: results of a phase 3 randomized study

Mitchell E. Horwitz, Patrick J. Stiff, Corey Cutler, Claudio Brunstein, Rabi Hanna, Richard T. Maziarz, Andrew R. Rezvani, Nicole A. Karris, Joseph McGuirk, David Valcarcel, Gary J. Schiller, Caroline A. Lindemans, William Y.K. Hwang, Liang Piu Koh, Amy Keating, Yasser Khaled, Nelson Hamerschlak, Olga Frankfurt, Tony Peled, Irit SegalovichBeth Blackwell, Stephen Wease, Laurence S. Freedman, Einat Galamidi-Cohen, Guillermo Sanz

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Omidubicel is an ex vivo expanded hematopoietic progenitor cell and nonexpanded myeloid and lymphoid cell product derived from a single umbilical cord blood unit. We report results of a phase 3 trial to evaluate the efficacy of omidubicel compared with standard umbilical cord blood transplantation (UCBT). Between January 2017 and January 2020, 125 patients age 13 to 65 years with hematologic malignancies were randomly assigned to omidubicel vs standard UCBT. Patients received myeloablative conditioning and prophylaxis with a calcineurin inhibitor and mycophenolate mofetil for graft-versus-host disease (GVHD). The primary end point was time to neutrophil engraftment. The treatment arms were well balanced and racially diverse. Median time to neutrophil engraftment was 12 days (95% confidence interval [CI], 10-14 days) for the omidubicel arm and 22 days (95% CI, 19-25 days) for the control arm (P < .001). The cumulative incidence of neutrophil engraftment was 96% for patients receiving omidubicel and 89% for patients receiving control transplants. The omidubicel arm had faster platelet recovery (55% vs 35% recovery by 42 days; P = .028), had a lower incidence of first grade 2 to 3 bacterial or invasive fungal infection (37% vs 57%; P = .027), and spent more time out of hospital during the first 100 days after transplant (median, 61 vs 48 days; P = .005) than controls. Differences in GVHD and survival between the 2 arms were not statistically significant. Transplantation with omidubicel results in faster hematopoietic recovery and reduces early transplant-related complications compared with standard UCBT. The results suggest that omidubicel may be considered as a new standard of care for adult patients eligible for UCBT. The trial was registered at www.clinicaltrials.gov as #NCT02730299.

Original languageEnglish (US)
Pages (from-to)1429-1440
Number of pages12
JournalBlood
Volume138
Issue number16
DOIs
StatePublished - Oct 21 2021

Bibliographical note

Funding Information:
The authors thank Bruno Boulanger and Elena Maurer from BPE for their contribution to the CD34 correlative analyses, and Sarah Anderson, Alice Henning, Shashidhar Joshy, Laura Morrison, and Amarnath Vijayarangan from the Emmes Company for their support for statistical analyses. This work was supported by funding from Gamida Cell.

Funding Information:
Conflict-of-interest disclosure: M.E.H. served as consultant to AbbVie, CareDx, and Magenta, received honoraria from Kadmon, and received research funding from Gamida Cell. P.J.S. served as a consultant to CRISPR and received research funding from Gamida Cell, Atara Biotherapeutics, Amgen, Incyte, Takeda, Macrogenics, and Eisai. C.C. served as a consultant and member of the board of directors or advisory committee for Incyte, Kadmon, Jazz Pharmaceuticals, Medsenic, Generon, and Mesoblast. C.B. received research funding from Magenta, Gamida Cell, and Astex and is an advisor to AlloVir. R.T.M. received research funding from Novartis and Juno, data safety monitoring board membership for Novartis and Athersys, received honoraria from Incyte, Kite Pharma, Bristol Myers Squibb/Celgene, PACT Pharma, Orca BioSystems, and Omeros, has patents with and receives royalties from Athersys, and served as a consultant for Novartis, Incyte, CRISPR Therapeutics, Artiva Biotherapeutics, and Allovir. A.R.R. received research funding from Pharmacyclics. J.M. received research funding from Novartis, Fresenius Biotech, Astellas, Bellicum Pharmaceuticals, Gamida Cell, and Pluristem, and received honoraria and served as a consultant for Kite Pharma, Juno, and AlloVir. G.J.S. served as a consultant for Agios, Amgen, AstraZeneca, Incyte, Novartis, and Ono, served on the speakers bureau for Celgene, Sanofi, Gilead, and Stemline, and received research funding from AbbVie, Actinium, Ariad, Astellas, Celgene, Celator, Constellation, Cyclacel, Daiichi Sankyo, Deciphera, DeltaFly, Forma, FujiFilm, Gamida Cell, Genentech, Roche, Geron, Jazz Pharmaceuticals, Karyopharm, Kite Pharma, Mateon, Medimmune, Onconova, Pfizer, Regimmune, Samus, Sangamo, Tolero, Trovagene, Kaiser Permanente, and Johnson & Johnson, and has equity in Bristol Myers Squibb and Pfizer. Y.K. was a member of the board of directors, advisory committee, or speakers bureau for Celgene, Seattle Genetics, Jazz Pharmaceuticals, and Takeda. G.S. served on an advisory committee for AbbVie, Hoffman-LaRoche, Helsinn, and Takeda. I.S. and E.G.-C. are employed by and have equity holdings in Gamida Cell. T.P. reports equity holdings in Gamida Cell. B.B. and S.W. are employed by Emmes Company. L.S.F. declares that Gertner Institute for Epidemiology and Health Policy Research received remuneration from Gamida Cell for the statistical consultation that he provided to the trial. The remaining authors declare no competing financial interests.

Publisher Copyright:
© 2021 American Society of Hematology

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