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Analysis of Outcomes and Predictors of Response in Patients with Relapsed Mantle Cell Lymphoma Treated with Brexucabtagene Autoleucel
Blood ; 138:1756, 2021.
Article in English | EMBASE | ID: covidwho-1582193
ABSTRACT

Background:

Brexucabtagene autoleucel (brexu-cel) is the first CD19 chimeric antigen receptor T-cell (CAR T) therapy approved for use in patients (pts) with relapsed mantle cell lymphoma (MCL). The ZUMA-2 trial demonstrated that brexu-cel induces durable remissions in these pts with an ORR of 85% (59% CR), estimated 12-month PFS rate of 61%, and similar toxicity profile to other CAR T therapies (Wang et al, NEJM 2020). We conducted a multicenter, retrospective study of pts treated with commercial brexu-cel to evaluate its safety and efficacy in the non-trial setting.

Methods:

We reviewed records of pts with relapsed MCL across 12 US academic medical centers. Pts who underwent leukapheresis between July 2020 and June 2021 with the intent to proceed to commercial brexu-cel were included. Baseline demographic and clinical characteristics were summarized using descriptive statistics. Survival curves were generated using the Kaplan-Meier method, and univariate models were fit to identify predictors of post-CAR T outcomes.

Results:

Fifty-five pts underwent leukapheresis. There were 3 manufacturing failures. Baseline characteristics of the 52 pts who received brexu-cel are summarized in Table 1. Median age was 66 yrs (range 47-79 yrs) and 82% were male. Twenty of 29 (69%) pts with known baseline MIPI were intermediate or high risk. Seven pts had a history of CNS involvement. The median number of prior therapies was 3 (range 2-8), including prior autologous stem cell transplant (ASCT) in 21 (40%) and prior allogeneic transplant in 2 pts (1 with prior ASCT and 1 without). Fifty percent had relapsed within 24 months of their initial therapy. All pts had previously received a Bruton's tyrosine kinase inhibitor (BTKi), including 29 (56%) with disease progression on a BTKi. Forty (77%) pts received bridging therapy (17 BTKi, 10 BTKi + venetoclax, 6 chemo, 3 venetoclax, 2 XRT only, 1 steroids only, 1 lenalidomide + rituximab). The ORR was 88% (CR 69%) among patients who received brexu-cel. Two pts had PD on initial restaging and 3 died prior to first response assessment (without evidence of relapse). Seven pts have not completed restaging due to limited follow-up (< 3 months) and were not included in the response assessment. Five pts have progressed, including 2 with CR and 1 with PR on initial restaging. With a median follow-up of 4.2 months, the estimated 6-month PFS and OS rates were 82.7% and 89.0%, respectively. All 7 pts with prior CNS involvement were alive without relapse at last follow-up. The incidence of cytokine release syndrome (CRS) was 84% (10% grade ≥ 3) with a median time to max grade of 5 days (range 0-10 days). There were no cases of grade 5 CRS. The incidence of neurotoxicity (NT) was 57% (31% grade ≥ 3) with a median time to onset of 7 days (range 4-15 days). NT occurred in 4/7 pts with prior CNS involvement (3 grade 3, 1 grade 4). Grade 5 NT occurred in 1 pt who developed cerebral edema and died 8 days after infusion. Thirty-five pts received tocilizumab, 33 received steroids, 7 received anakinra, and 1 received siltuximab for management of CRS and/or NT. Post-CAR T infections occurred in 8 pts, including two grade 5 infectious AEs (covid19 on day +80 and septic shock on day +40 after infusion). Rates of grade ≥ 3 neutropenia and thrombocytopenia were 38% and 37%, respectively. Among pts with at least 100 days of follow-up and lab data available, 5/34 (15%) had persistent grade ≥ 3 neutropenia and 4/34 (12%) had persistent grade ≥ 3 thrombocytopenia at day +100. Five pts have died, with causes of death being disease progression (2), septic shock (1), NT (1), and covid19 (1). Univariate analysis did not reveal any significant associations between survival and baseline/pre-CAR T MIPI, tumor pathologic or cytogenetic features, prior therapies, receipt of steroids/tocilizumab, or pre-CAR T tumor bulk.

Conclusions:

This analysis of relapsed MCL pts treated with commercial brexu-cel reveals nearly identical response and toxicity rates compared to those reported on ZUMA-2. Longer follow-up is require to confirm durability of response, but these results corroborate the efficacy of brexu-cel in a population of older adults with high-risk disease features. While all 7 pts with prior CNS involvement are alive and in remission, strategies to mitigate the risk of NT in this setting need to be evaluated. Further studies to define the optimal timing of CAR T, bridging strategies, and salvage therapies for post-CAR T relapse in MCL are warranted. [Formula presented] Disclosures Gerson TG Therapeutics Consultancy;Kite Consultancy;Abbvie Consultancy;Pharmacyclics Consultancy. Sawalha TG Therapeutics Consultancy, Research Funding;Celgene/BMS Research Funding;BeiGene Research Funding;Epizyme Consultancy. Bond Kite/Gilead Honoraria. Karmali Janssen/Pharmacyclics Consultancy;BeiGene Consultancy, Speakers Bureau;Morphosys Consultancy, Speakers Bureau;Takeda Research Funding;Genentech Consultancy;AstraZeneca Speakers Bureau;Roche Consultancy;Karyopharm Consultancy;Epizyme Consultancy;Kite, a Gilead Company Consultancy, Research Funding, Speakers Bureau;BMS/Celgene/Juno Consultancy, Research Funding;EUSA Consultancy. Torka TG Therapeutics Membership on an entity's Board of Directors or advisory committees. Chow ADC Therapeutics Current holder of individual stocks in a privately-held company, Research Funding;AstraZeneca Research Funding. Shadman Abbvie, Genentech, AstraZeneca, Sound Biologics, Pharmacyclics, Beigene, Bristol Myers Squibb, Morphosys, TG Therapeutics, Innate Pharma, Kite Pharma, Adaptive Biotechnologies, Epizyme, Eli Lilly, Adaptimmune, Mustang Bio and Atara Biotherapeutics Consultancy;Mustang Bio, Celgene, Bristol Myers Squibb, Pharmacyclics, Gilead, Genentech, Abbvie, TG Therapeutics, Beigene, AstraZeneca, Sunesis, Atara Biotherapeutics, GenMab Research Funding. Ghosh Genentech Research Funding;Pharmacyclics LLC, an AbbVie Company Consultancy, Honoraria, Research Funding, Speakers Bureau;Karyopharma Consultancy, Honoraria;Seattle Genetics Consultancy, Honoraria, Speakers Bureau;Janssen Consultancy, Honoraria, Speakers Bureau;TG Therapeutics Consultancy, Honoraria, Research Funding;Incyte Consultancy, Honoraria;Gilead Consultancy, Honoraria, Research Funding, Speakers Bureau;Genmab Consultancy, Honoraria;Epizyme Honoraria, Speakers Bureau;Bristol Myers Squibb Consultancy, Honoraria, Research Funding, Speakers Bureau;AstraZeneca Consultancy, Honoraria, Speakers Bureau;ADC Therapeutics Consultancy, Honoraria;Adaptive Biotech Consultancy, Honoraria;AbbVie Honoraria, Speakers Bureau. Moyo Seattle Genetics Consultancy. Fenske TG Therapeutics Consultancy, Speakers Bureau;Servier Pharmaceuticals Consultancy;Seattle Genetics Speakers Bureau;Sanofi Speakers Bureau;Pharmacyclics Consultancy;MorphoSys Consultancy;Kite (Gilead) Speakers Bureau;KaryoPharm Consultancy;CSL Therapeutics Consultancy;Bristol-Myers Squibb Speakers Bureau;Biogen Consultancy;Beigene Consultancy;AstraZeneca Speakers Bureau;ADC Therapeutics Consultancy;Adaptive Biotechnologies Consultancy;AbbVie Consultancy. Grover Genentech Research Funding;Novartis Consultancy;ADC Other Advisory Board;Kite Other Advisory Board;Tessa Consultancy. Maddocks Seattle Genetics Divested equity in a private or publicly-traded company in the past 24 months;BMS Divested equity in a private or publicly-traded company in the past 24 months;Pharmacyclics Divested equity in a private or publicly-traded company in the past 24 months;Novatis Divested equity in a private or publicly-traded company in the past 24 months;Janssen Divested equity in a private or publicly-traded company in the past 24 months;Morphosys Divested equity in a private or publicly-traded company in the past 24 months;ADC Therapeutics Divested equity in a private or publicly-traded company in the past 24 months;Karyopharm Divested equity in a private or publicly-traded company in the past 24 months;Beigene Divested equity in a private or publicly-traded company in the past 24 months;Merck Divested equity in a private or publicly-traded company in the past 24 months;KITE Divested equity in a private or publicly-traded company in the past 24 months;Celgene Divested equity in a private or publicly-traded company in the past 24 months. Jacobson Kite, a Gilead Company Consultancy, Honoraria, Other Travel support;Humanigen Consultancy, Honoraria, Other Travel support;Celgene Consultancy, Honoraria, Other Travel support;Pfizer Consultancy, Honoraria, Other Travel support, Research Funding;Lonza Consultancy, Honoraria, Other Travel support;AbbVie Consultancy, Honoraria;Precision Biosciences Consultancy, Honoraria, Other Travel support;Novartis Pharmaceuticals Corporation Consultancy, Honoraria, Other Travel support;Nkarta Consultancy, Honoraria;Axis Speakers Bureau;Clinical Care Options Speakers Bureau. Cohen Janssen, Adaptive, Aptitude Health, BeiGene, Cellectar, Adicet, Loxo/Lilly, AStra ZenecaKite/Gilead Consultancy;Genentech, Takeda, BMS/Celgene, BioInvent, LAM, Astra Zeneca, Novartis, Loxo/Lilly Research Funding.
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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study Language: English Journal: Blood Year: 2021 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study Language: English Journal: Blood Year: 2021 Document Type: Article