Evidence map›Paper›PMID 37648261›Full record

ArticleJournal for immunotherapy of cancer2023

Impact of prior therapies and subsequent transplantation on outcomes in adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3.

Bijal D Shah, Ryan D Cassaday, Jae H Park, Roch Houot, Olalekan O Oluwole, Aaron C Logan, Nicolas Boissel, Thibaut Leguay, Michael R Bishop, Max S Topp and 19 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 2 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

29 authors.

Bijal D Shah *Division of Hematology/Oncology, Department of Malignant Hematology, Moffitt Cancer Center, Tampa, Florida, USA Bijal.Shah@moffitt.org.ORCID 0000-0003-4328-6021
Ryan D CassadayFred Hutchinson Cancer Center, University of Washington, Seattle, Washington, USA.ORCID 0000-0002-3424-2425
Jae H ParkDepartment of Medicine, Memorial Hospital, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Roch HouotDepartment of Hematology, CHU Rennes, University Hospital Rennes, Inserm & EFS, Rennes, France.
Olalekan O OluwoleVanderbilt-Ingram Cancer Center, Division of Hematology and Oncology, Vanderbilt University, Nashville, Tennessee, USA.
Aaron C LoganHelen Diller Comprehensive Cancer Center, University of California San Francisco, San Francisco, California, USA.
Nicolas BoisselDépartement d'Hématologie Clinique, Hôpital Saint-Louis, Paris, France.
Thibaut LeguayDepartment of Hematology, Service d'hématologie clinique et thérapie cellulaire Hôpital du Haut-Leveque CHU de Bordeaux, Bordeaux, France.
Michael R BishopThe David and Etta Jonas Center for Cellular Therapy, The University of Chicago Medicine, Chicago, Illinois, USA.
Max S ToppMedizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Wurzburg, Germany.
Dimitrios TzachanisMoores Cancer Center, University of California San Diego, San Diego, California, USA.
Kristen M O'DwyerWilmot Cancer Institute, University of Rochester, Rochester, New York, USA.
Martha L ArellanoWinship Cancer Institute, Emory University, Atlanta, Georgia, USA.
Yi LinDepartment of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Maria R BaerMarlene and Stewart Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland, USA.
Gary J SchillerDavid Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Marion SubkleweDepartment of Medicine III, Ludwig-Maximilians-Universität München, Munich, Germany.
Mehrdad AbediDavis Comprehensive Cancer Center, University of California, Sacramento, California, USA.
Monique C MinnemaDepartment of Hematology, University Medical Centre Utrecht, Utrecht, The Netherlands.
William G WierdaDepartment of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Daniel J DeAngeloDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Patrick J StiffDepartment of Hematology/Oncology, Loyola University Medical Center, Maywood, Illinois, USA.
Deepa JeyakumarChao Comprehensive Cancer Center, University of California Irvine Medical Center, Irvine, California, USA.
Daqin MaoKite, a Gilead Company, Santa Monica, California, USA.
Sabina AdhikaryKite, a Gilead Company, Santa Monica, California, USA.
Lang ZhouKite, a Gilead Company, Santa Monica, California, USA.
Petra C SchuberthKite, a Gilead Company, Santa Monica, California, USA.
Rita Damico KhalidKite, a Gilead Company, Santa Monica, California, USA.
Armin Ghobadia *Division of Medical Oncology, Washington University School of Medicine in Saint Louis, St Louis, Missouri, USA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundBrexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported.

methodsEligible adults had R/R B-ALL and received one infusion of brexu-cel (1×10⁶ CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided.

resultsPhase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7-58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups.Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22).

conclusionsIn ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel.

Indexed as

Hematopoietic Stem Cell TransplantationPrecursor Cell Lymphoblastic Leukemia-LymphomaAdaptor Proteins, Signal TransducingAdultAntigens, CD19Cytokine Release SyndromeHumansImmunotherapy, AdoptiveReceptors, Chimeric AntigenAdaptor Proteins, Signal TransducingAntigens, CD19brexucabtagene autoleucelReceptors, Chimeric AntigenCell EngineeringCytotoxicity, ImmunologicHematologic NeoplasmsImmunity, CellularImmunotherapy

Identifiers

PMID37648261
PMCPMC10471850

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.