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Multicenter Study
. 2025 Aug 26;9(16):4081-4089.
doi: 10.1182/bloodadvances.2024015779.

Outcomes of brexucabtagene autoleucel in patients with relapsed/refractory acute lymphoblastic leukemia with CNS involvement

Ibrahim N Muhsen  1 , Gregory W Roloff  2 , Rawan Faramand  3 , Tamer Othman  4 , Yannis Valtis  5 , Noam E Kopmar  6 , Simone E Dekker  6 , Matthew Connor  7 , Santiago Mercadal  8 , Timothy E O'Connor  9 , Kaitlyn C Dykes  10 , Mohamed Ahmed  11 , Nikeshan Jeyakumar  12 , Amy Zhang  12 , Katharine Miller  12 , Katherine C Sutherland  12 , Caitlin Guzowski  13 , Vishal K Gupta  14 , Navneet Majhail  15 , Minoo Battiwalla  15 , Melhem M Solh  13 , Shahbaz A Malik  16 , John Mathews  17 , Caspian H Oliai  14 , Paul Shaughnessy  18 , Luke Mountjoy  19 , Catherine J Lee  8 , Aaron C Logan  4 , Stephanie B Tsai  9 , Jessica T Leonard  20 , Marc Schwartz  21 , Joshua P Sasine  11 , Muthu Kumaran  22 , Noelle Frey  7 , Jae H Park  5 , Divya Koura  10 , Ryan D Cassaday  6 , Bijal D Shah  3 , Ibrahim Aldoss  23 , Lori S Muffly  12 , LaQuisa C Hill  1
Affiliations
Multicenter Study

Outcomes of brexucabtagene autoleucel in patients with relapsed/refractory acute lymphoblastic leukemia with CNS involvement

Ibrahim N Muhsen et al. Blood Adv. .

Abstract

Patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) with central nervous system (CNS) involvement (CNS B-ALL) have poor outcomes and were frequently excluded from CD19-targeting chimeric antigen receptor (CAR) T-cell clinical trials. The efficacy and safety of brexucabtagene autoleucel (brexu-cel) in adults with R/R B-ALL was established by the ZUMA-3 trial, which excluded patients with advanced or symptomatic CNS involvement. In this retrospective multicenter analysis, we investigated the safety and efficacy of brexu-cel in patients with CNS B-ALL using data from the ROCCA (Real-World Outcomes Collaborative for CAR T in ALL) consortium. Of 189 patients who received infusion, 31 had CNS-2 (presence of blasts in cerebrospinal fluid with <5 white blood cells [WBCs] per μL) or CNS-3 (presence of blasts with >5 WBCs per μL and/or clinical signs/symptoms) disease before apheresis and are the focus of this report. The median age was 46.5 years (range, 24-76), and 58.1% were male. Most (87.1%) received bridging therapy. After brexu-cel, 21 of 24 patients with CNS restaging (87.5%) achieved CNS-1. Additionally, 28 of 30 evaluable patients achieved marrow complete remission; 25 were measurable residual disease negative. No statistically significant differences were seen in progression-free survival or overall survival after brexu-cel among patients with or without CNS involvement. Similarly, grade 3/4 immune effector cell-associated neurotoxicity syndrome occurred similarly in patients with (35.5%) and without (30%) CNS disease. In conclusion, our data suggest that brexu-cel results in high response rates in patients with CNS B-ALL, with toxicity comparable with that in patients without CNS involvement.

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Conflict of interest statement

Conflict-of-interest disclosure: G.W.R. served on an advisory board for Kite and Autolus. R.F. reports research funding from Kite/Gilead and Novartis; advisory board member role with Kite/Gilead and Autolus; and consulting role with Sanofi. N.M. reports membership on an entity’s board of directors or advisory committees for Anthem Inc. M.B. received research funding from Novartis and Fate Therapeutics. M.M.S. reports speakers bureau role with Bristol Myers Squibb (BMS). P.S. received honoraria from Autolus Therapeutics and BMS; and reports speakers bureau role with BMS and Sanofi. C.J.L. reports consultancy with Fresenius Kabi, Sanofi, and Incyte Corp; received honoraria from Kite Pharma, BMS, Sanofi, and Kadmon; served as an advisory board member with Kite Pharma, Sanofi, and Incyte Corp; reports speakers bureau role with Kite Pharma; and received research funding from Incyte Corp. A.C.L. reports research funding from Amgen, Astellas, Autolus Therapeutics, Kadmon, Kite/Gilead, Pharmacyclics, and Talaris; and consultancy with AbbVie, Amgen, Actinium, BMS, Pfizer, Sanofi, and Takeda. S.B.T. reports speakers bureau role with BMS and Jazz Pharmaceuticals; and served on an advisory board for Autolus. J.T.L. reports consultancy with Adaptive Biotechnologies, Pfizer, Kite/Gilead, and Takeda; and membership on an entity’s board of directors or advisory committees with, and travel, accommodations, and expenses from, Adaptive Biotechnologies. C.H.O. received research funding from Electra, Novartis, Arog, Orca Bio, Jazz Pharmaceuticals, Pfizer, and Seagen. M.S. reports consultancy with Jazz Pharmaceuticals, Kite, and Autolus. J.P.S. reports consultancy with Kite/Gilead Autolus, and Genmab. D.K. reports consultancy with, and research funding from, BMS. R.D.C. received research funding from Servier, Incyte, Kite/Gilead, Amgen, Vanda Pharmaceuticals, Jazz Pharmaceuticals, Merck, and Pfizer; served on advisory committees of PeproMene Bio and Autolus; reports consultancy with, and honoraria from, Kite/Gilead, Amgen, Jazz Pharmaceuticals, and Pfizer; and reports employment (spouse) with, and stock ownership in, Seagen, within the last 24 months. B.D.S. reports research funding from Incyte, Jazz Pharmaceuticals, Kite/Gilead, and Servier; received honoraria from Pharmacyclics/Janssen, Spectrum/Acrotech, BeiGene, and Gilead Sciences; reports current employment with Moffitt Cancer Center; served on a data and safety monitoring board of, and received travel and accommodations and expenses from, Celgene, Novartis, Pfizer, Janssen, Seattle Genetics, AstraZeneca, Stemline Therapeutics, and Kite/Gilead; reports membership on an entity’s board of directors or advisory committees with PeproMene Bio; and reports consultancy with Takeda, AstraZeneca, Adaptive Biotechnologies, BMS/Celgene, Novartis, Pfizer, Amgen, Precision Biosciences, Kite/Gilead, Jazz Pharmaceuticals, Century Therapeutics, Deciphera, Autolus Therapeutics, Lilly, and PeproMene Bio. I.A. reports consultancy with Kite, Sobi, Jazz, Pfizer, Amgen, and Takeda; received honoraria from Amgen; served on an advisory board with Amgen, Pfizer, Jazz, Kite, Takeda, Syndax, Sobi, and Wugen; and received research support from AbbVie and MacroGenics. L.S.M. reports consultancy with Amgen, Pfizer, Kite, Astellas, and Autolus; received research funding from BMS, Adaptive, Kite, Autolus, Astellas, Orca Bio, and Jasper; received honoraria from Kite; and reports membership on an entity’s board of directors or advisory committees with Adaptive. L.C.H. reports consulting for, and membership on an entity’s board of directors or advisory committees of, March Biosciences; serves as a speaker for Kite/Gilead; and reports honoraria from Sanofi. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
Response rates at preapheresis assessment and day +28 after infusion. (A) Medullary response rates are shown. A total of 28 patients achieved CR, of whom 25 achieved CR with MRD-negative status. Of 13 patients with active disease at preapheresis, 11 achieved MRD-negative CR. (B) CNS responses are shown; 21 of 24 evaluable patients achieved a response, whereas 3 patients had refractory disease (1 with CNS-2 disease and 2 with CNS-3 disease).
Figure 2.
Figure 2.
Survival outcomes in patients with and without CNS involvement. Of the initial 31 patients with CNS B-ALL who received infusion, 8 patients died during a median follow-up of 13.8 months. (A) PFS and (B) OS are shown. No statistically significant differences were noted between the outcomes in patients with and without CNS disease.
Figure 3.
Figure 3.
Flow diagram for the treatment and responses of patients with CNS B-ALL in our retrospective analysis. DLI, donor lymphocyte infusion; MOF, multiorgan failure.
See this image and copyright information in PMC

References

    1. Surapaneni UR, Cortes JE, Thomas D, et al. Central nervous system relapse in adults with acute lymphoblastic leukemia. Cancer. 2002;94(3):773–779. - PubMed
    1. Reman O, Pigneux A, Huguet F, et al. GET-LALA group Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis and/or at first relapse: results from the GET-LALA group. Leuk Res. 2008;32(11):1741–1750. - PubMed
    1. Fielding AK, Richards SM, Chopra R, et al. Medical Research Council of the United Kingdom Adult ALL Working Party. Eastern Cooperative Oncology Group Outcome of 609 adults after relapse of acute lymphoblastic leukemia (ALL); an MRC UKALL12/ECOG 2993 study. Blood. 2007;109(3):944–950. - PubMed
    1. Kopmar NE, Cassaday RD. How I prevent and treat central nervous system disease in adults with acute lymphoblastic leukemia. Blood. 2023;141(12):1379–1388. - PMC - PubMed
    1. Aldoss I, Otoukesh S, Zhang J, et al. Extramedullary disease relapse and progression after blinatumomab therapy for treatment of acute lymphoblastic leukemia. Cancer. 2022;128(3):529–535. - PubMed

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