Impact of Autoimmune Disease on Toxicity and Outcomes after Axicabtagene Ciloleucel in Patients with Diffuse Large B Cell Lymphoma

Background:

Axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, has the potential to cure patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). However, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common treatment-related adverse events. Historically, patients with autoimmune conditions have been excluded from CAR-T trials. This study evaluated differences in CRS, ICANS, relapse, and survival between patients with or without autoimmune disease who received axi-cel for R/R DLBCL.

Methods:

A retrospective study of patients with R/R DLBCL who received commercial axi-cel at Moffitt Cancer Center in Tampa, FL between 2015-2023 was conducted to identify patients with pre-existing autoimmune conditions. Clinically significant autoimmune conditions requiring medical management prior to axi-cel infusion included rheumatoid arthritis, systemic lupus erythematosus, Graves' disease, ulcerative colitis, ITP, autoimmune encephalitis, psoriasis, scleroderma, psoriatic arthritis, polymyalgia rheumatica, Behcet's syndrome, and type 1 diabetes. Cumulative incidence of CRS and ICANS was calculated for patients with and without autoimmune disease. Cox proportional hazards model and Kaplan-Meier estimates were used to study the impact of autoimmune disease on survival after CD19 CAR-T cell therapy.

Results:

Out of 279 patients with R/R DLBCL who received axi-cel, 20 patients (7%) had a clinically significant autoimmune disease. Among these 20 patients, median age was 70 years (range, 41 - 78 years), and 14 were female (70%). The incidence of any grade and severe (grade ≥3) CRS among patients with an autoimmune disease was 85% and 0%, respectively, versus 90% and 5.5% in patients without an autoimmune disease (p = 0.692).

The incidence of any grade and severe (grade ≥3) ICANS in these patients was 60% and 25%, respectively, with a median duration of 3 days (range, 1 - 61 days), versus 58% and 24% with a median duration of 4 days (range, 1 to 92 days) for patients without autoimmune disease (n = 259). The incidence (p = 1) and duration (p = 0.74) of ICANS was not significantly different in those with or without autoimmune disease.

Among patients with autoimmune disease, overall survival (OS) at 3 years was significantly lower than patients without autoimmune conditions, HR 2.08, 95% CI 1.17 - 3.68, (p = 0.010). The leading cause of death for autoimmune patients was lymphoma progression.

The OS for patients with autoimmune disease who experienced ICANS was significantly lower than patients without autoimmune conditions who experienced ICANS (p = 0.05). Among patients who experienced any ICANS, patients with autoimmune disease did appear to have lower progression free survival (PFS) than patients without autoimmune disease, but this was not statistically significant (p = 0.07). Among patients who did not experience any ICANS, there was no significant difference in OS (p = 0.1) or PFS (p = 0.7) between patients with or without autoimmune disease.

Conclusions:

This single institutional experience showed that pre-existing autoimmune disease did not seem to impact incidence or duration of CRS or ICANS in patients with R/R DLBCL who were treated with commercial axi-cel. However, patients with autoimmune disease who experienced ICANS had worse outcomes. Having autoimmune disease was associated with significantly lower survival, albeit from a limited sample size. Although risks of toxicity are relatively comparable, patients with autoimmune disease may benefit from close monitoring after receiving axi-cel. Future studies will explore the management of immunosuppression among patients with autoimmune disease before, during, and after CAR-T cell therapy.

Lazaryan:Sanofi: Consultancy, Honoraria, Other: Scientific advisory board. Faramand:Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Autolus: Membership on an entity's Board of Directors or advisory committees; Orca Bio: Research Funding; Sanofi: Consultancy, Honoraria. Freeman:Abbvie: Consultancy; Sanofi: Consultancy; Incyte: Consultancy; Amgen: Consultancy; Seattle Genetics: Consultancy; Janssen: Consultancy, Research Funding; Roche/Genentech: Research Funding; Celgene: Consultancy; BMS: Consultancy, Honoraria, Research Funding; ONK therapeutics: Consultancy. Shah:Eli Lilly: Consultancy; Kite Pharma: Consultancy; Jazz Pharmaceuticals: Consultancy; Bristol Myers Squibb: Consultancy; Adaptive Biotechnologies: Consultancy; Amgen: Consultancy; Autolus, Beigene, Century Therapeutics, Deciphera, Jazz, Kite/Gilead, Pfizer, Precision Biosciences, Novartis, Takeda: Consultancy; AstraZeneca: Consultancy; Jazz Pharmaceuticals, Kite-Gilead, Servier: Research Funding; Pepromene Bio: Other: DSMB. Gaballa:BeiGene: Consultancy; Genentech: Consultancy; AstraZeneca: Consultancy; ADC Therapeutics: Consultancy, Honoraria; AbbVie: Consultancy; Genmab: Consultancy; Gilead: Consultancy; Eli Lilly: Honoraria; Regeneron: Consultancy; Ipsen: Consultancy. Chavez:BeiGene: Consultancy, Honoraria, Speakers Bureau; GenMab: Consultancy, Research Funding; Merck: Research Funding; Abbvie: Consultancy; Novartis: Consultancy; Allogene: Consultancy; AstraZeneca: Consultancy; Lilly: Honoraria, Speakers Bureau; Janssen: Honoraria; Cellectis: Consultancy; Kite, a Gilead Company: Consultancy; ADC Therapeutics: Consultancy. Locke:Moffitt Cancer Center: Patents & Royalties; BioPharma Communications CARE Education: Honoraria; Kite, a Gilead Company: Consultancy, Other: institutional, travel, accomodation, expenses, Research Funding; Bluebird Bio: Consultancy; American Society of Hematology: Honoraria, Other: travel, accomodation, expenses; Calibr: Consultancy; Amgen: Consultancy; A2: Consultancy; Caribou: Consultancy; Society for Immunotherapy of Cancer: Honoraria; EcoR1: Consultancy; Cowen: Consultancy; Clinical Care Options Oncology: Honoraria; Bristol-Myers Squibb: Consultancy, Research Funding; Allogene: Consultancy, Research Funding; Allogene: Other: Institutional, Research Funding; Gerson Lehrman Group (GLG): Consultancy; Imedex: Honoraria; Communications CARE Education: Honoraria; Iovance: Consultancy; Janssen: Consultancy; Legend Biotech: Consultancy; Novartis: Consultancy, Research Funding; Sana: Consultancy; Umoja: Consultancy; Pfizer: Consultancy; 2SeventyBio: Other: Institutional, Research Funding; CERo Therapeutics: Research Funding; Aptitude Health: Honoraria; National Cancer Institute: Other: Institutional, Research Funding; Leukemia and Lymphoma Society Scholar in Clinical Research: Other: Institutional, Research Funding. Jain:Loxo: Research Funding; Myeloid Therapeutics: Consultancy; Incyte: Research Funding; Kite/Gilead: Consultancy, Research Funding. Nishihori:Medexus: Membership on an entity's Board of Directors or advisory committees; ImmunoGen: Consultancy; Karyopharm: Other: drug only supply to the institution; Novartis: Research Funding. Mirza:BMS: Speakers Bureau.