Single-dose CAR-T therapy potentially curative in multiple myeloma

A multi-institutional study led by the Icahn School of Medicine at Mount Sinai reports one-third of patients with relapsed or refractory multiple myeloma remained in remission for at least five years following a single infusion of the CAR-T cell therapy cilta-cel.

Multiple myeloma is a blood cancer that responds well to initial treatments, yet often relapses or becomes resistant. It is especially difficult to treat in patients who have undergone multiple prior lines of therapy.

Historical data show median progression-free survival under six months and overall survival near one year for these individuals. Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor (CAR) T-cell therapy, has demonstrated more durable responses in earlier follow-ups of the CARTITUDE-1 trial.

In the study, “Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma,” published in Journal of Clinical Oncology, researchers conducted a post hoc analysis to evaluate overall survival, sustained remission, associated immunologic biomarkers, and safety outcomes following treatment with a single cilta-cel infusion.

A total of 97 patients with relapsed or refractory multiple myeloma (RRMM), each previously treated with at least three lines of therapy and nearly all triple-class refractory, received a single cilta-cel infusion between July 2018 and October 2019 across multiple clinical sites.

Survival and progression were tracked using Kaplan-Meier methods over a median follow-up of 61.3 months. Of the 97 patients, 32 (33% of the cohort) remained alive and progression-free five years after infusion, with no maintenance therapy. Nearly all (31 of the 32) achieved stringent complete response (disease remission) by independent review.

In addition, 12 patients at a single center underwent serial evaluations and were minimal residual disease-negative and imaging-negative at year five or later.

Patients who remained progression-free showed trends toward lower tumor burden, higher hemoglobin and platelet counts at baseline, and higher proportions of naive T cells in the infused product. They also had higher effector-to-target ratios and greater peak expansion of CAR-positive T cells, along with more favorable T cell–to–neutrophil ratios.

Safety remained consistent with previous reports, with no new cases of parkinsonism or cranial nerve palsies. Among long-term responders, two second primary malignancies, two neurologic events, and four grade 3 or higher infections were reported.

Investigators describe these findings as the longest reported follow-up for CAR-T therapy in multiple myeloma to date and interpret them as evidence of potentially curative outcomes in a subset of patients.

Clinical trials are under way to assess cilta-cel in earlier lines of therapy, with the goal of expanding long-term, treatment-free survival to more patients.

© 2025 Science X Network

A multi-institutional study led by the Icahn School of Medicine at Mount Sinai reports one-third of patients with relapsed or refractory multiple myeloma remained in remission for at least five years following a single infusion of the CAR-T cell therapy cilta-cel.

Multiple myeloma is a blood cancer that responds well to initial treatments, yet often relapses or becomes resistant. It is especially difficult to treat in patients who have undergone multiple prior lines of therapy.

Historical data show median progression-free survival under six months and overall survival near one year for these individuals. Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor (CAR) T-cell therapy, has demonstrated more durable responses in earlier follow-ups of the CARTITUDE-1 trial.

In the study, “Long-Term (≥5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma,” published in Journal of Clinical Oncology, researchers conducted a post hoc analysis to evaluate overall survival, sustained remission, associated immunologic biomarkers, and safety outcomes following treatment with a single cilta-cel infusion.

A total of 97 patients with relapsed or refractory multiple myeloma (RRMM), each previously treated with at least three lines of therapy and nearly all triple-class refractory, received a single cilta-cel infusion between July 2018 and October 2019 across multiple clinical sites.

Survival and progression were tracked using Kaplan-Meier methods over a median follow-up of 61.3 months. Of the 97 patients, 32 (33% of the cohort) remained alive and progression-free five years after infusion, with no maintenance therapy. Nearly all (31 of the 32) achieved stringent complete response (disease remission) by independent review.

In addition, 12 patients at a single center underwent serial evaluations and were minimal residual disease-negative and imaging-negative at year five or later.

Patients who remained progression-free showed trends toward lower tumor burden, higher hemoglobin and platelet counts at baseline, and higher proportions of naive T cells in the infused product. They also had higher effector-to-target ratios and greater peak expansion of CAR-positive T cells, along with more favorable T cell–to–neutrophil ratios.

Safety remained consistent with previous reports, with no new cases of parkinsonism or cranial nerve palsies. Among long-term responders, two second primary malignancies, two neurologic events, and four grade 3 or higher infections were reported.

Investigators describe these findings as the longest reported follow-up for CAR-T therapy in multiple myeloma to date and interpret them as evidence of potentially curative outcomes in a subset of patients.

Clinical trials are under way to assess cilta-cel in earlier lines of therapy, with the goal of expanding long-term, treatment-free survival to more patients.

© 2025 Science X Network