Autoimmune Outcomes in Patients with Concurrent Autoimmune Disease Receiving CD19- or BCMA-Targeted CAR T-Cell Therapy for Lymphoma or Multiple Myeloma

Abstract

Introduction

Chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of lymphoma and myeloma. Recent studies indicate that CAR-T may have significant activity in refractory autoimmune disease (AID). We sought to determine the impact of CAR-T on AID.

Methods

This is a retrospective, single-center analysis of patients with a history of AID who received commercial CD19- or BMCA- targeted CAR T-cells for lymphoma or multiple myeloma at Fred Hutchinson Cancer Center from 1/2018-5/2024. Products included axicabtagene ciloleucel, brexucabtagene autoleucel, ciltacabtagene autoleucel, idecabtagene vicleucel, lisocabtagene maraleucel, and tisagenlecleucel. AID manifestations were graded on subjective improvement or exacerbation of symptoms and adjustment of treatment.

Results

Of the 386 patients who have received CD19- or BCMA- directed CAR-T, we identified a total of 35 patients with concurrent AID (Table 1). The oncologic complete response rate was 62.9% (n=22) by day +30 post-CAR-T, and 40.0% (n=14) experienced relapsed disease.

Twenty-eight patients had a history of treatment for their AID with 18 patients on active therapy at time of their lymphoma or multiple myeloma diagnosis. Ten patients remained on AID-directed treatment during their cancer-targeted treatment, and 8 patients remained on active treatment at time of CAR T-cell therapy (Figure 1A-C).

Of the 8 patients on active therapy for their AID, all whom received CD19-targeted CAR-T, 4 (50%) experienced an improvement in their disease status after CAR-T. Three patients discontinued or decreased the intensity of their AID-directed therapy without exacerbation of symptoms at time of last follow-up (range: 12-30 months post CAR-T). The fourth patient experienced improvement in symptom burden but remained on treatment (last follow-up 2 months post-CAR-T). Meanwhile, three patients (37.5%), all asymptomatic at the time of CAR-T, continued on their prior regimen. One patient (12.5%) experienced exacerbation of their symptoms though did not require systemic therapy. Two patients who were not on AID-directed therapy at time of CAR T-cell therapy experienced exacerbation of their disease within the first month after infusion but neither required treatment.

Conclusion

In our center's experience, half of patients on active treatment for AID prior to CAR-T experienced improvement in AID symptoms and/or cessation or decrease in intensity of AID-directed therapy. Worsening of AID, a feared complication with CAR-T, is fortunately uncommon. CAR-T 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 for patients with AID. They also dispute the notion that concomitant AID should exclude patients who are otherwise candidates for this treatment.