Single-Dose CAR-T Therapy Shows Promise as Potential Cure for Multiple Myeloma

A recent study spearheaded by the Icahn School of Medicine at Mount Sinai has unveiled promising results regarding the use of a single-dose CAR-T cell therapy, cilta-cel, in patients with relapsed or refractory multiple myeloma. The findings indicate that approximately one-third of the participants maintained remission for at least five years following just one infusion of this innovative treatment.

Multiple myeloma is a complex blood cancer that often responds favorably to initial treatments but can relapse or develop resistance, making it particularly challenging to manage in patients who have undergone several lines of therapy. Historical data suggests that these patients generally experience a median progression-free survival of less than six months, with overall survival rates nearing one year.

Ciltacabtagene autoleucel (cilta-cel), a form of chimeric antigen receptor (CAR) T-cell therapy, has exhibited more durable responses in earlier follow-ups of the CARTITUDE-1 trial. The study titled Long-Term (>=5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma, published in the Journal of Clinical Oncology, involved a post hoc analysis assessing overall survival, sustained remission, immunologic biomarkers, and safety outcomes following a single cilta-cel infusion.

In total, 97 patients with relapsed or refractory multiple myeloma, who had previously received at least three lines of therapy and were predominantly triple-class refractory, underwent a single infusion of cilta-cel between July 2018 and October 2019 across various clinical sites.

Survival and progression metrics were evaluated using Kaplan-Meier methods over a median follow-up period of 61.3 months. Of the 97 patients, 32--accounting for 33% of the cohort--remained alive and progression-free five years post-infusion, all without the need for maintenance therapy. Remarkably, 31 of these 32 patients achieved a stringent complete response, indicating a complete remission of the disease.

Additionally, a subset of 12 patients at a single center exhibited both minimal residual disease negativity and imaging negativity at the five-year mark or later. Those who remained free from progression demonstrated trends towards a reduced tumor burden, increased baseline hemoglobin and platelet counts, as well as a higher proportion of naive T cells in the infused product. Furthermore, they showed elevated effector-to-target ratios and significant peak expansion of CAR-positive T cells, along with more favorable T cell-to-neutrophil ratios.

Safety assessments were consistent with prior reports, revealing no new incidents of parkinsonism or cranial nerve palsies. Among the long-term responders, recorded adverse events included two second primary malignancies, two neurological events, and four instances of infections rated as grade 3 or higher.

The investigators highlighted these results as the longest documented follow-up for CAR-T therapy in multiple myeloma thus far, suggesting potentially curative outcomes for a select group of patients. Ongoing clinical trials are evaluating the use of cilta-cel in earlier treatment lines, aiming to extend the benefits of long-term, treatment-free survival to a broader patient population.

For more detailed insights, refer to the original publication: Sundar Jagannath et al, Long-Term (>=5-Year) Remission and Survival After Treatment With Ciltacabtagene Autoleucel in CARTITUDE-1 Patients With Relapsed/Refractory Multiple Myeloma, Journal of Clinical Oncology (2025). DOI: 10.1200/JCO-25-00760