Dataset Information

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy.

ABSTRACT: We conducted a phase I clinical trial of anti-BCMA chimeric antigen receptor T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later-line therapy (phase A, N = 10) or high-risk patients responding to first-line therapy (phase B, N = 20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade cytokine release syndrome (CRS) and only one instance of low-grade neurologic toxicity. Among 15 subjects with measurable disease, 10 exhibited partial response (PR) or better; among 26 subjects responding to prior therapy, 9 improved their response category and 4 converted to minimal residual disease (MRD)-negative complete response/stringent complete response. Early maintenance therapy was safe, feasible, and coincided in some patients with CAR T-cell reexpansion and late-onset, durable clinical response. Outcomes with CART-BCMA + huCART19 were similar to CART-BCMA alone. Collectively, our results demonstrate favorable safety, pharmacokinetics, and antimyeloma activity of dual-target CAR T-cell therapy in early lines of MM treatment.

Significance

CAR T cells in early lines of MM therapy could be safer and more effective than in the advanced setting, where prior studies have focused. We evaluated the safety, pharmacokinetics, and efficacy of CAR T cells in patients with low disease burden, responding to current therapy, combined with standard maintenance therapy. This article is highlighted in the In This Issue feature, p. 101.

SUBMITTER: Garfall AL

PROVIDER: S-EPMC9975770 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy.

Garfall Alfred L AL Cohen Adam D AD Susanibar-Adaniya Sandra P SP Hwang Wei-Ting WT Vogl Dan T DT Waxman Adam J AJ Lacey Simon F SF Gonzalez Vanessa E VE Fraietta Joseph A JA Gupta Minnal M Kulikovskaya Irina I Tian Lifeng L Chen Fang F Koterba Natalka N Bartoszek Robert L RL Patchin Margaret M Xu Rong R Plesa Gabriela G Siegel Don L DL Brennan Andrea A Nelson Anne Marie AM Ferthio Regina R Cosey Angela A Shea Kim-Marie KM Leskowitz Rachel R Four Megan M Wilson Wesley V WV Miao Fei F Lancaster Eric E Carreno Beatriz M BM Linette Gerald P GP Hexner Elizabeth O EO Young Regina M RM Bu Dexiu D Mansfield Keith G KG Brogdon Jennifer L JL June Carl H CH Milone Michael C MC Stadtmauer Edward A EA

Blood cancer discovery 20230301 2

We conducted a phase I clinical trial of anti-BCMA chimeric antigen receptor T cells (CART-BCMA) with or without anti-CD19 CAR T cells (huCART19) in multiple myeloma (MM) patients responding to third- or later-line therapy (phase A, N = 10) or high-risk patients responding to first-line therapy (phase B, N = 20), followed by early lenalidomide or pomalidomide maintenance. We observed no high-grade cytokine release syndrome (CRS) and only one instance of low-grade neurologic toxicity. Among 15 su ...[more]

PMID: 36413381

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Project description:BackgroundCAR-T-cell therapy and bispecific antibody have revolutionized the treatment landscape for multiple myeloma. However, there is currently a lack of studies comparing the efficacy and safety of these two approaches. This meta-analysis assesses the efficacy and safety of B-cell maturation antigen (BCMA)-directed CAR-T-cell therapies and BCMA×CD3 bispecific antibodies as third-line or later interventions for relapsed/refractory multiple myeloma (RRMM).MethodsWe searched PubMed, Embase, Web of Science, and Cochrane databases up to May 31, 2024, identifying 11 eligible studies encompassing 1269 participants. Random-effects models evaluated the primary (complete response (CR) rate) and secondary (overall response rate (ORR)) outcomes, while meta-regression analyses adjusted for relevant covariates.ResultsCAR-T-cell therapy achieved significantly higher pooled CR rate (0.54 (95% CI 0.42-0.69) vs bispecific antibodies 0.35 (0.30-0.41), p<0.01) and pooled ORR (0.83 (0.76-0.90) vs 0.65 (0.59-0.71), p<0.01). However, CAR-T therapy had a higher incidence of adverse events, particularly cytokine release syndrome (CRS 0.83 (0.70-0.97) vs bispecific antibodies 0.59 (0.43-0.74), p<0.05). Severe CRS (grade ≥3) occurred at a rate of 0.07 (0.03-0.14) in the CAR-T cell group, contrasting with a negligible rate of 0.01 (0.00-0.02) in the bispecific antibody group (p<0.01). Hematologic adverse events, including neutropenia (grade ≥3; 0.88 (0.81-0.95) vs 0.48 (0.30-0.67), p<0.01) and anemia (grade≥3; 0.55 (0.47-0.62) vs 0.34 (0.28 to 0.40), p<0.01), were also more frequent in the CAR-T-cell group. Furthermore, differences in efficacy were observed among various CAR-T products, with ciltacabtagene autoleucel showing greater efficacy in CR rate (0.77 (0.71-0.84) vs 0.37 (0.32-0.41), p<0.01) and ORR (0.91 (0.83-0.99) vs 0.73 (0.68-0.77), p<0.01) compared with idecabtagene vicleucel.ConclusionCAR-T-cell therapy demonstrated superior CR rates compared with bispecific antibodies, although with an increase in severe adverse events.

Project description:The present study aimed to study the efficacy and adverse effects of anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy in relapsed or refractory multiple myeloma. Patients were divided into three dose groups based on cell therapy concentration. After CAR-T cell therapy for 10 patients with recurrent or refractory multiple myeloma, the patients were monitored and evaluated regularly to observe the efficacy and adverse reactions of CAR-T cell therapy. At a median follow-up of 337 (253-504) days, one patient succumbed 24 days due to rapidly progressing disease. The overall response rate of nine patients was 88.9%, including 77.8% (7/9) with minimal residual disease negative complete remission (CR) and 11.1% (1/9) with partial remission. A total of three patients were maintained in remission state for more than a year and eight were maintained for more than six months. Among the three patients with extramedullary invasion, two extramedullary lesions disappeared and one was stable. The highest copy number of CAR-T cells in seven patients with CR was >1x105 copies/µl gDNA, and the best therapeutic effect can be achieved within 30 (7-30) days after the copy number of CAR-T cells reached 1x105 copies/µl genomic DNA. The median onset time in the nine patients was 43 (22-169) days, and the median progression-free survival was 337 (253-504). Among the 10 patients, nine (90%) had cytokine release syndrome, all of which were below grade II. There were nine (90%) patients with hematological adverse reactions, six (60%) patients with severe anemia, five (50%) patients with grade III and above leukopenia, five (50%) patients with granulocytopenia, four (40%) patients with grade III and above thrombocytopenia, and three (30%) patients with grade III and above pancytopenia. It was concluded that anti-BCMA CAR-T cell therapy is a promising treatment method for relapsed or refractory multiple myeloma and extramedullary invasion, with stable efficacy and controllable adverse effects.

Dataset Information

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy.

Significance

Publications

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy.

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