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Multicenter Study
. 2024 Dec 10;8(23):6139-6147.
doi: 10.1182/bloodadvances.2024013747.

Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL

Ibrahim Aldoss  1 , Gregory W Roloff  2 , Rawan Faramand  3 , Noam E Kopmar  4 , Chenyu Lin  5 , Anjali S Advani  6 , Simone E Dekker  4   7 , Vishal K Gupta  8 , Timothy E O'Connor  9 , Nikeshan Jeyakumar  10 , Ibrahim N Muhsen  11 , Yannis Valtis  12 , Amy Zhang  10 , Katharine Miller  10 , Katherine Sutherland  10 , Kaitlyn C Dykes  13 , Mohamed Ahmed  14 , Evan Chen  15 , Hector Zambrano  16 , Danielle Bradshaw  17 , Santiago Mercadal  18 , Marc Schwartz  19 , Sean Tracy  20 , Bhagirathbhai Dholaria  21 , Michal Kubiak  17 , Akash Mukherjee  22 , Navneet Majhail  23 , Minoo Battiwalla  23 , Luke Mountjoy  24 , Shahbaz A Malik  25 , John Mathews  26 , Paul Shaughnessy  27 , Aaron C Logan  28 , Abdullah Ladha  29 , Maryann Stefan  6 , Caitlin Guzowski  30 , Rasmus T Hoeg  31 , Talal Hilal  32 , Jozal Moore  33 , Matthew Connor  34 , Kristen M O'Dwyer  33 , LaQuisa C Hill  11 , Stephanie B Tsai  9 , Joshua Sasine  14 , Melhem M Solh  30 , Catherine J Lee  18 , Vamsi K Kota  17 , Divya Koura  13 , Muthu Veeraputhiran  35 , Betsy Blunk  23 , Caspian Oliai  8 , Jessica T Leonard  7 , Noelle V Frey  34 , Jae H Park  12 , Marlise R Luskin  15 , Veronika Bachanova  20 , Ahmed Galal  5 , Michael R Bishop  2 , Wendy Stock  2 , Ryan D Cassaday  4 , Vinod Pullarkat  1 , Bijal D Shah  3 , Lori S Muffly  10
Affiliations
Multicenter Study

Impact of prior inotuzumab ozogamicin treatment on brexucabtagene autoleucel outcomes in adults with B-cell ALL

Ibrahim Aldoss et al. Blood Adv. .

Abstract

The effect of prior inotuzumab ozogamicin (InO) treatment on brexucabtagene autoleucel (brexu-cel) outcomes remains unclear in adults with acute lymphoblastic leukemia (ALL). We conducted a retrospective multicenter analysis of 189 patients with relapsed/refractory ALL treated with brexu-cel. Over half of the patients received InO before brexu-cel (InO exposed). InO-exposed patients were more heavily pretreated (P = .02) and frequently had active marrow disease before apheresis (P = .03). Response rate and toxicity profile after brexu-cel were comparable for InO-exposed and InO-naïve patients; however, consolidation therapy after brexu-cel response was used at a higher rate in InO-naïve patients (P = .005). With a median follow-up of 11.4 months, InO-exposed patients had inferior progression-free survival (PFS; P = .013) and overall survival (OS; P = .006) in univariate analyses; however, prior InO exposure did not influence PFS (hazard ratio, 1.20; 95% confidence interval, 0.71-2.03) in multivariate models. Within InO-exposed patients, InO responders had superior PFS (P = .002) and OS (P < .0001) relative to InO-refractory patients. The timing of administering InO did not affect brexu-cel outcomes, with comparable PFS (P = .51) and OS (P = .86) for patients receiving InO as bridging therapy or before apheresis. In conclusion, although InO exposure was associated with inferior survival outcomes after brexu-cel in unadjusted analyses, these associations were no longer significant in multivariate analyses, suggesting it is unlikely that InO negatively affects brexu-cel efficacy. Our data instead imply that InO-exposed recipients of brexu-cel tend to be higher-risk patients with intrinsic adverse leukemia biology.

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Conflict of interest statement

Conflict-of-interest disclosure: I.A. reports consultancy fees from Syndax, Wugen, Kite, Sobi, Jazz, Pfizer, and Takeda; consultancy fees and honoraria from Amgen; advisory board fees from Amgen, Pfizer, Jazz, Kite, Takeda, Syndax, Sobi, and Wugen; and research support from AbbVie and Macrogenics. R.F. reports research funding and advisory board membership fees from Kite/Gilead and research funding from Novartis. C.L. reports consultancy fees from Rigel Pharmaceuticals; being current equity holder in a publicly traded company, BioMarin; and advisory board fees from Autolus. A.S.A. reports research funding from Servier, ImmunoGen, OBI, Incyte, Seattle Genetics, and MacroGenics; honoraria and other including consulting fees and research funding from Kite; membership on an entity’s board of directors or advisory committees and research funding from GlycoMimetics; honoraria and research funding from Pfizer; honoraria from and membership on an entity’s board of directors or advisory committees in Jazz; honoraria from Beam, Nkarta, and Kura; honoraria from and membership on an entity’s board of directors or advisory committees in Taiho and Novartis; and honoraria and other including advisory board fees and research funding from Amgen. E.C. reports consultancy fees from AbbVie. M.S. reports consultancy fees from Jazz Pharmaceuticals, Kite, and Autolus. B.D. reports consultancy fees from BEAM Therapeutics, Pluri Biotech, Boxer Capital, Gamida Cell, Ellipsis Pharma, Lumanity, and Arivan; research funding from Atara, Molecular Templates, AstraZeneca, MEI, Gilead, Angiocrine, Adicet, Takeda, Poseida, Pfizer, Bristol Myers Squibb (BMS), Wugen, Orca Bio, Poseida, Allovir, and NCI; consultancy fees and honoraria from ADC Therapeutics; and consultancy fees, honoraria, and research funding from Janssen. N.M. reports membership on an entity’s board of directors or advisory committees in Anthem Inc. M.B. reports research funding from Novartis and Fate Therapeutics. P.S. reports honoraria from Autolus Therapeutics and BMS, and speakers' bureau fees from BMS and Sanofi. A.C.L. reports research funding from Amgen, Astellas, Autolus Therapeutics, Kadmon, Kite/Gilead, Pharmacyclics, and Talaris, and consultancy fees from AbbVie, Amgen, Actinium, BMS, Pfizer, Sanofi, and Takeda. A.L. reports consultancy fees from Pfizer and CTI Biopharma. R.T.H. reports research funding from Orca Bio. T.H. reports consultancy fees and research funding (to institution) from BeiGene. L.C.H. reports consulting fees from March Biosciences and speaker fees from Kite/Gilead. S.B.T. reports speakers' bureau fees from BMS and Jazz Pharmaceuticals, and advisory board fees from Autolus. M.M.S. reports speaker's bureau fees from BMS. C.J.L. reports consultancy fees from Fresenius Kabi; honoraria, advisory board member fees, and speaker's bureau fees from Kite Pharma; honoraria from BMS; consultancy fees, advisory board member fees, and honoraria from Sanofi; honoraria from Kadmon; and consultancy fees, advisory board member fees, and research funding from Incyte Corp. V.K.K. reports honoraria from Pfizer, Novartis, and Kite, and research funding from Incyte. D.K. reports consultancy fees and research funding from BMS. J.T.L. reports consultancy fees, membership on an entity’s board of directors or advisory committees in, and other fundings including travel, accommodations, and expenses from Adaptive Biotechnologies, and consultancy fees from Pfizer, Kite/Gilead, and Takeda. C.O. reports research funding from Novartis, Arog, Orca Bio, Jazz Pharmaceuticals, Pfizer, and Seagen. V.B. reports research funding from Citius, BMS, Incyte, and Gamida Cell; membership on an entity’s board of directors or advisory committees in AstraZeneca, ADC, and Allogene; other funding including data and safety monitoring board from Miltenyi; and advisory board member fees from AstraZeneca, Allogene, BeiGene, and CRISPR. W.S. reports consultancy fees from Kite and GlaxoSmithKline; consultancy fees and honoraria from Jazz Pharmaceuticals; honoraria from Amgen and Newave; research funding from Kura; and other funding including data safety monitoring board/advisory board fees from Servier. R.D.C. reports research funding from Servier, Incyte, Vanda Pharmaceuticals, and Merck; membership on an entity’s board of directors or advisory committees in PeproMene Bio and Autolus; consultancy fees, honoraria, and research funding from Kite/Gilead, Amgen, Jazz Pharmaceuticals, and Pfizer; and other interest including spouse being employed by and owned stock in Seagen within the last 24 months. V.P. reports consultancy fees and speakers' bureau fees from Servier, Amgen, Pfizer, Jazz Pharmaceuticals, Novartis, Genentech, and AbbVie. B.D.S. reports research funding from Incyte, Jazz Pharmaceuticals, Kite/Gilead, and Servier; honoraria from Pharmacyclics/Janssen, Spectrum/Acrotech, BeiGene, and Gilead Sciences; current employment with Moffitt Cancer Center; other funding including travel, accommodations, and expenses from Celgene, Novartis, Pfizer, Janssen, Seattle Genetics, AstraZeneca, Stemline Therapeutics, and Kite/Gilead; membership on an entity’s board of directors or advisory committees and data and safety monitoring committee in PeproMene Bio; and consultancy fees from Takeda, AstraZeneca, Adaptive Biotechnologies, BMS/Celgene, Novartis, Pfizer, Amgen, Precision BioSciences, Kite/Gilead, Jazz Pharmaceuticals, Century Therapeutics, Deciphera, Autolus Therapeutics, Lilly, and PeproMene Bio. L.S.M. reports consultancy from Amgen, Pfizer, and Autolus; research funding from BMS, Orca Bio, and Jasper; membership on an entity’s board of directors or advisory committees in and research funding from Adaptive; consultancy fees, honoraria, and research funding from Kite; and consultancy fees and research funding from Astellas. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Treatment flow diagram.
Figure 2.
Figure 2.
Post-brexu-cel survival outcomes based on InO-exposure and response. (A) PFS by prior InO exposure (naïve vs exposed). (B) OS by prior InO exposure (naïve vs exposed). (C) PFS by prior InO exposure and response to InO (naïve vs InO exposed and responded vs InO exposed and nonresponder). (D) OS by prior InO exposure and response to InO (naïve vs InO exposed and responded vs InO exposed and nonresponder).
Figure 3.
Figure 3.
Multivariate analysis for association of demographic-, disease-, and treatment-specific characteristics, including prior InO response, with PFS in the study cohort.
See this image and copyright information in PMC

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