Prophylactic Corticosteroid Use with Axicabtagene Ciloleucel (axi-cel) in Patients with Relapsed/Refractory Large B-Cell Lymphoma (R/R LBCL): Real-World Practice Patterns and Outcomes

Introduction: To minimize toxicities associated with axi-cel, several exploratory safety management cohorts were added to the ZUMA-1 study. In cohort 6 (n = 40), prophylactic (ppx) corticosteroid (CS) use beginning on day 0 was assessed as an intervention strategy to decrease grade ≥ 3 cytokine release syndrome (CRS)/ immune effector cell associated neurotoxicity (ICANS). No grade ≥3 CRS was observed and Grade ≥3 ICANS was observed in 13% of cases without any difference in objective response rate (ORR) or complete response rate (CR) when compared to cohorts that did not use ppx treatment. Based on these findings, the FDA approved an update to the prescribing information for axi-cel to include use of ppx CS across all approved indications in January 2022. However, ppx CS use is not a mandatory standard treatment and has not been universally adopted. We sought to establish the real-world practice patterns of ppx CS use and clinical outcomes.

Methods: To assess real-world practice patterns of ppx CS use with axi-cel for R/R LBCL, we sent a 5-question survey to 22 centers across the US axi-cel certified treatment centers. Next, to assess the clinical outcomes of pts receiving ppx CS, we conducted a multicenter retrospective review of pts with R/R LBCL undergoing axi-cel since the FDA approval for prophylactic indication. Baseline characteristics were compared between the no ppx vs. the ppx CS groups. Axi-cel-related toxicities CRS and ICANS were graded based on ASTCT 2019 guidelines. Updated data will be presented at the meeting with more pts and longer follow up.

Results: Of the 22 centers, 17 (77%) responded to the questionnaire, with 11/22 (50%) using ppx CS (figure 1). Six centers that had not adopted the ppx steroids cited various reasons such as limited data on efficacy, presence of clinical trial using ppx CS, and unclear effect on CAR-T expansion. 7 of 11 centers using ppx CS only use it for a subset of patients and 3 of 11 use it in all patients receiving axi-cel. The subset of patients selected for ppx CS was based on general institutional guidelines or treating physician preference. Criteria for those with institutional guidelines were variable but included high disease burden, older patients with comorbidities, and those requiring chemotherapy for bridging.

A total of 22 pts at 4 centers received axi-cel between Jan 31, 2022, and June 15, 2022. A historical cohort of 22 pts was added to the no ppx CS group for those infused in 2021. Eleven (58%) pts received ppx CS and baseline characteristics at the time of apheresis are shown in Table 1. These were comparable between the 2 groups except for a shorter median time from apheresis to CAR-T infusion in the no ppx CS group. Among the entire cohort, 71% of patients required bridging therapy and only 20% (9/44) met ZUMA-1 eligibility criteria at the time of lymphodepletion. Any grade CRS occurred in 91% (40/44) pts, with grade ≥2 CRS in 43% (19/44). Any grade ICANS occurred in 61% (27/44) pts, with grade ≥2 ICANS in 43% (19/44) pts. The rates of grade ≥2 CRS, ICANS, the median time to CRS onset, ICANS onset, CRS duration, and ICANS duration were comparable between the 2 groups. Ten pts (23%) developed infectious complications within 30 days of CART. The day 30 ORR was 80% and was comparable between the 2 groups. In the ppx CS group (n = 22), 5 pts had progressed and 2 had died (both disease progression) at the time of data cut-off. Median event-free survival and overall survival had not been reached in either group (excluding historical cohort), due to short median follow-up of 15 weeks.

Conclusions: Real-world adoption of ppx CS to mitigate toxicities of axi-cel varies considerably across sites in the US for multiple reasons. Since the FDA label change at least 50% of the centers surveyed had adopted the use of ppx CS. No significant differences in efficacy or CAR-T-associated toxicities were noted in the 2 groups, potentially due to selective use with patients at presumed higher risk of severe CRS and ICANS. A larger dataset and longer follow-up is needed for risk-stratified analysis and will be presented at the meeting.

Lee:CareDx: Consultancy; Fresensius Kabi: Consultancy; Jazz: Consultancy; Kite: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kadmon: Consultancy, Membership on an entity's Board of Directors or advisory committees. Hunter:Kite Pharma: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria; Notable Labs: Consultancy, Honoraria; Genmab: Consultancy, Honoraria. Lunning:AbbVie: Consultancy; Acrotech: Consultancy; ADC Therapeutics: Consultancy; Astra-Zeneca: Consultancy; Diiachi-Sankyo: Consultancy; Janssen: Consultancy; Kite, a Gilead Company: Consultancy; Morphosys: Consultancy; TG Therapeutics: Consultancy; Astellas: Consultancy; BMS: Consultancy, Research Funding; EUSA: Consultancy; Fate Therapeutics: Consultancy; Genentech: Consultancy; Genmab: Consultancy; Nurix Therapeutics: Consultancy; Seattle Genetics: Consultancy; CURIS: Research Funding; Pharmacyclics: Consultancy. Jaglowski:Gamida: Consultancy; Novartis: Research Funding; Kite: Consultancy, Research Funding; CRISPR Therapeutics: Consultancy. Jain:BMS: Consultancy; MyeloidTx: Consultancy; Incyte: Research Funding; Novartis: Consultancy; Kite Pharma: Consultancy, Research Funding. Bachanova:Gamida Cell: Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharma: Consultancy; Citius Pharma: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Incyte: Research Funding; FATA Therapeutics: Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees. Farooq:Kite, a Gilead Company: Honoraria; MorphoSys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Caribou pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Checkmate Pharma: Research Funding. Ahmed:Servier: Membership on an entity's Board of Directors or advisory committees; Chimagen: Consultancy, Research Funding; Xencor: Research Funding; Tessa Therapeutics: Consultancy, Research Funding; Seagen: Research Funding; Merck: Research Funding; Myeloid Therapeutics: Consultancy. Hill:Novartis: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support, Research Funding; BMS: Consultancy, Honoraria, Research Funding. Munoz:Pharmacyclics/Abbvie, Bayer, Gilead/Kite Pharma, Pfizer, Janssen, Juno/Celgene, BMS, Kyowa, Alexion, Fosunkite, Innovent, Seattle Genetics, Debiopharm, Karyopharm, Genmab, ADC Therapeutics, Epizyme, Beigene, Servier, Novartis, Morphosys/Incyte, Mei pharma: Consultancy; Bayer, Gilead/Kite Pharma, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium: Research Funding; Targeted Oncology, OncView, Curio, Kyowa, Physicians’ Education Resource, Dava, Global clinical insights, MJH, Shanghai Youyao, and Seattle Genetics: Honoraria; Gilead/Kite Pharma, Kyowa, Bayer, Pharmacyclics/Janssen, Seattle Genetics, Acrotech/Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/BMS, Genentech/Roche: Speakers Bureau. Patel:Abbvie: Consultancy; Adaptive Biotechnologies: Research Funding; ADC Therapeutics: Consultancy; Aptevo Therapeutics: Research Funding; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; BeiGene: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Caribou Biosciences: Consultancy; Celgene: Consultancy, Research Funding, Speakers Bureau; CRISPR Therapeutics: Research Funding; Curis, Inc: Research Funding; Epizyme: Consultancy, Research Funding; Fate Therapeutics: Research Funding; Genetech/Roche: Consultancy, Research Funding, Speakers Bureau; Kite pharma: Consultancy, Research Funding, Speakers Bureau; Loxo Oncology: Consultancy, Research Funding; MEI Pharma: Consultancy, Research Funding; Morphosys: Consultancy; Nurix: Research Funding; Pharmacyclics/Janssen: Consultancy, Research Funding, Speakers Bureau; Sunesis Pharmaceuticals: Research Funding; TG Therapeutics: Consultancy, Speakers Bureau; Trillium Therapuetics/Pfizer: Consultancy, Research Funding; Velos Bio: Research Funding; Xencor: Consultancy, Research Funding. Oluwole:TG Therapeutics: Consultancy; Kite, a Gilead Company: Research Funding; Janssen: Consultancy; Curio Science: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; ADC Therapeutics: Consultancy. Lin:Janssen: Consultancy, Research Funding; Juno: Consultancy; Vineti: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; Novartis: Consultancy; Legend: Consultancy; Merck: Research Funding; Sorrento: Consultancy; Gamida Cell: Consultancy; Celgene: Consultancy, Research Funding; Bluebird Bio: Consultancy, Research Funding; Takeda: Research Funding.