Immune Synergy May Explain Why Some Patients Achieve Durable Remission With Cilta-Cel

A Mount Sinai study may reveal why some patients with multiple myeloma (MM) receiving ciltacabtagene autoleucel (cilta-cel; Carvykti, Janssen Biotech, Inc/Legend Biotech) achieve prolonged remission. The researchers report that remission is dependent on the synergy between the patient’s immune system and the infused chimeric antigen receptor (CAR) T cells.

“This research shows that long remissions depend not only on the CAR-T cells we give but also on the patient’s own immune system,” said Alessandro Lagana, PhD, Assistant Professor of Oncological Sciences at the Icahn School of Medicine at Mount Sinai and senior author of the study.¹

MM is a complex and challenging disease, marked by diminishing responses with each successive line of therapy and no known cure. Over the past two decades, patient outcomes have improved substantially with the introduction of novel and more advanced treatments. Among these, cilta-cel has emerged as a particularly notable breakthrough in the myeloma treatment landscape.²

Cilta-cel, one of two FDA-approved BCMA-directed CAR T-cell therapies, activates and expands T cells to eradicate tumor cells and recruit additional immune cells to the cancer site. Initially approved in 2022 for heavily pretreated patients and expanded in 2024 to those with at least 1 prior line of therapy, cilta-cel demonstrated an impressive 98% overall response rate and a median response duration of 21.8 months in the CARTITUDE-1 trial (NCT03548207). At the median follow-up of 61.3 months, 33% of patients were alive and progression-free without the need for maintenance treatment following a single infusion.^2,3

The trial outcomes are pivotal for MM, leading experts to investigate the underlying mechanism driving this remission milestone. They published their findings in Blood Advances.⁴

“CAR T-cell therapy has changed myeloma care, but not everyone maintains a long remission,” said Lagana. “We wanted to understand what’s happening in the immune system of patients who stay in remission for more than 5 years after a single infusion.”¹

The team followed 19 patients from the CARTITUDE-1 who received cilta-cel and assessed their blood and bone marrow samples before and after treatment. The tests showed that patients with longer-lasting responses showed an early, concentrated expansion of CAR T cells along with a broad, diverse pool of healthy helper (CD4) T cells that stayed active over time.¹

In contrast, those who relapsed more quickly tended to have a higher baseline tumor burden and an early increase in immunosuppressive myeloid cells, which can dampen T-cell activity.¹

The team believes a better understanding of immune patterns may help clinicians and pharmacists better select patients for CAR T-cell therapy and monitor for relapse. Further studies are needed, but these initial findings pave the way for improved treatment management.

REFERENCES

1. Mount Sinai study reveals why some myeloma patients stay cancer-free for years after car t therapy. Mount Sinai. November 12, 2025. Accessed November 17, 2025. https://www.mountsinai.org/about/newsroom/2025/mount-sinai-study-reveals-why-some-myeloma-patients-stay-cancer-free-for-years-after-car-t-therapy

2. Gerlach A. Can cilta-cel redefine outcomes in multiple myeloma? Pharmacy Times. August 6, 2025. Accessed November 17, 2025. https://www.pharmacytimes.com/view/can-cilta-cel-redefine-outcomes-in-multiple-myeloma-

3. A study of JNJ-68284528, a chimeric antigen receptor T cell (CAR-T) therapy directed against B-cell maturation antigen (BCMA) in participants with relapsed or refractory multiple myeloma (CARTITUDE-1). Updated July 30, 2025. Accessed November 17, 2025. https://www.clinicaltrials.gov/study/NCT03548207#study-overview

4. Vieira dos Santos J, Melnekoff DT, Aleman A, et al. Long-term remission after cilta-cel in multiple myeloma is linked to diverse t cells and low myeloid suppression. Blood Adv. November 5, 2025. Doi: 10.1182/bloodadvances.2025018078