Autoimmune Outcomes in Patients with Concurrent Autoimmune Disease Receiving CD19 CAR T-Cell Therapy for Lymphoma

Introduction:

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of relapsed/refractory B- and plasma-cell malignancies. Recent studies indicate that CD19 CAR T-cell therapy may have significant activity in refractory autoimmune disease (AID).

We identified patients at Fred Hutchinson Cancer Center (FHCC) with a concurrent AID diagnosis in addition to their lymphoma for which they received CD19-targeted CAR T-cell therapy. We tracked their AID outcomes post CAR T-cell infusion to determine whether this treatment impacted their AID.

Methods:

This is a retrospective, single-center analysis of patients with a history of AID who received commercially available CD19-targeted CAR T-cells for lymphoma at FHCC from January 2018 to May 2024. Products included axicabtagene ciloleucel (axi-cel), brexucabtagene autoleucel (brexu-cel), lisocabtagene maraleucel (liso-cel), and tisagenlecleucel (tisa-cel). We extracted the past medical history from the immunotherapy consult notes, a comprehensive review of the patient's oncologic and other medical history, for AID identification. For longitudinal assessment of AID, we also reviewed patient charts and our long term-follow up database.

Results:

Of the 300 patients who have received axi-cel, brexu-cel, liso-cel, or tisa-cel, we identified a total of 32 patients (10.7%; axi-cel, n=14; brexu-cel, n=2; liso-cel, n=14; tisa-cel, n=2) with concurrent AID. Four patients had more than one AID. Of the patients with AIDs,13 were rheumatologic (systemic lupus erythematous [SLE], n=5; rheumatoid arthritis [RA], n=6); 8 were dermatologic (psoriasis, n=6); 6 neurologic (multiple sclerosis, n=4); 3 were hematologic (autoimmune hemolytic anemia, n=2; anti-phospholipid syndrome, n=1); 2 were gastrointestinal; and 3 were paraneoplastic. The complete response rate was 62.5% (n=20) by day +30 post-CAR T-cell therapy, and 4.3% (n=13) experienced relapsed disease.

Twenty-five patients had a history of treatment for their AID with 17 patients on active therapy at time of their lymphoma diagnosis. Nine patients stopped or decreased therapy due to the larger immunosuppressive effect of their lymphoma-directed treatment while 8 patients remained on active therapy at time of CAR T-cell therapy (e.g. hydroxychloroquine, oral steroids, sulfasalazine, glolimumab, or topical steroids).

Of the 8 patients on active therapy for their AID, 4 experienced an improvement in their disease status after CAR T-cell infusion. Three patients discontinued or decreased the intensity of their AID-directed therapy without exacerbation of symptoms at time of last follow-up (time points: 12 months, 18 months, and 30 months post CAR T-cell therapy). Two of these patients had SLE, and one had RA. Medications that were discontinued included hydroxychloroquine, rituximab, and sulfasalazine. The fourth patient, who had paraneoplastic cold agglutinin disease, experienced improvement in symptom burden but remained on sutimlimab (last follow-up 2 months post-CAR T-cell therapy). Meanwhile, three patients, all asymptomatic, at the time of CAR T-cell infusion, continued on their prior regimen. One patient, who had plaque psoriasis, experienced exacerbation of their symptoms after CAR T-cell therapy within the first year of CAR T-cell infusion, though did not require systemic therapy. Of the entire cohort of 25 patients, there were reports of improvement in symptoms after chemotherapy (n=4) and autologous stem cell transplant (n=3) prior to CAR T-cell therapy.

Rates of CAR T-cell associated toxicity included 13 patients (41%) with grade ≥ 2 cytokine release syndrome and 9 patients (28%) with grade ≥ 2 immune effector cell-associated neurotoxicity syndrome per American Society for Transplantation and Cellular Therapy criteria.

Conclusion:

Four of 8 patients (50%) on active treatment prior to CAR T-cell therapy experienced improvement in AID symptoms and/or cessation or decrease in intensity of AID-directed therapy. Three patients (37.5%) were asymptomatic but continued on AID treatment. Worsening of AID did occur in 1 patient (12.5%). CAR T-cell therapy may be a potential treatment option for patients with severe AID. Although our study was limited by a small sample size, these data support prospective trials to determine both the efficacy and toxicity of CAR-T cell therapy for patients with AID.

Shadman:Bristol Myers Squibb (spouse): Current Employment; Morphosys/Incyte: Consultancy, Research Funding; Kite Pharma: Consultancy; Eli Lilly: Consultancy; Fate therapeutics: Consultancy; Nurix: Consultancy; Merck: Consultancy; Mustang Bio: Research Funding; Vincerx: Research Funding; Koi Biotherapeutics: Current holder of stock options in a privately-held company; Bristol Myers Squibb: Consultancy; BeiGene: Consultancy, Research Funding; Janssen: Consultancy; Genmab: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding. Liang:Glass Health: Consultancy. Vinaud Hirayama:Nektar Therapeutics: Research Funding; Juno Therapeutics, a Bristol Myers Squibb Company: Honoraria, Research Funding. Cassaday:PeproMene Bio: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Honoraria, Research Funding; Jazz: Consultancy; Incyte: Research Funding; Autolus: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Seagen: Ended employment in the past 24 months; Servier: Consultancy, Research Funding; Vanda Pharmaceuticals: Research Funding. Gopal:Merck: Consultancy, Honoraria, Research Funding; I-Mab bio: Research Funding; IgM Bio: Research Funding; Takeda: Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Astra Zeneca: Research Funding; Agios: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding; BMS: Research Funding; SeaGen: Research Funding; Teva: Research Funding; Genmab: Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Morphosys/Incyte: Consultancy, Honoraria; ADCT: Consultancy, Honoraria; Acrotech: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Servier: Consultancy, Honoraria; Cellectar: Consultancy, Honoraria; Compliment: Consultancy, Current holder of stock options in a privately-held company, Honoraria; Epizyme: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; Caribou: Consultancy, Honoraria; Fresenius-Kabi: Consultancy, Honoraria; Scitek: Consultancy, Honoraria; Sana: Consultancy, Honoraria. Till:Mustang Bio: Consultancy, Patents & Royalties, Research Funding; Bristol Myers Squibb: Research Funding. Warren:Roche Diagnostics: Other: Travel Support. Gauthier:Sobi, Juno Therapeutics, a BMS company, Celgene, and Angiocrine Bioscience: Research Funding; Sobi, Legend Biotech, Janssen, Kite Pharma, a Gilead company, and MorphoSys: Consultancy. Maloney:Navan Technologies: Current equity holder in private company, Honoraria; Lyell Immunopharma: Honoraria; Interius: Honoraria; ImmPACT Bio: Honoraria; Gilead Sciences: Honoraria; Chimeric Therapeutics: Honoraria; Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Consultancy; Genentech: Consultancy, Honoraria; Caribou Biosciences: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Novartis: Honoraria; Celgene: Research Funding; Juno Therapeutics: Patents & Royalties: rights to royalties from Fred Hutch for patents licensed to Juno, Research Funding; Legend Biotech: Research Funding; A2 Biotherapeutics: Current holder of stock options in a privately-held company.