Treatment with a single infusion of ciltacabtagene autoleucel (cilta-cel; Carvykti) has demonstrated “quite remarkable” long-term remission and survival outcomes in heavily pretreated patients with relapsed/refractory multiple myeloma, indicating the curative potential of this agent, according to Peter Voorhees, MD.
Five-year follow-up data from the phase 1b/2 CARTITUDE-1 trial (NCT03548207) were presented at the 2025 ASCO Annual Meeting, and showed that 33% of patients who received cilta-cel were treatment- and progression-free at 5 years or longer.1 Notably, patients enrolled onto the trial had previously received 3 or more lines of therapy.2
“Now that we have a median follow-up that extends just beyond 5 years, the median overall survival [OS] in this group of patients is [60.7 months], which is really quite remarkable,” Voorhees emphasized during an interview with OncLive®. “In the LocoMMotion study [NCT04035226]…the median OS was 12.4 months [in patients with relapsed/refractory multiple myeloma treated with cilta-cel].3 To extend that out to 5 years [in CARTITUDE-1] is [significant], and is 5 times longer than we would have expected in this patient population.”
In the interview, Voorhees discussed the background and rationale for evaluating the 5-year remission and survival after cilta-cel infusion, key efficacy and safety data from this analysis, and the clinical implications of these data for cilta-cel use in relapsed/refractory multiple myeloma.
Voorhees is a member of the Hematology Department at Atrium Health Levine Cancer Institute and a professor of cancer medicine at the Wake Forest University School of Medicine in Charlotte, North Carolina.
OncLive: What was the background and rationale for evaluating the long-term remission and survival rates following cilta-cel administration in heavily pretreated relapsed/refractory multiple myeloma?
Voorhees: CARTITUDE-1 was a phase 1b/2, study that evaluated the safety and efficacy of the BCMA-targeted CAR T-cell therapy, cilta-cel, for patients with relapsed/refractory multiple myeloma. This was specifically for patients who were triple-class exposed, in other words, they’d been treated previously with CD38 antibodies, PIs, and IMiDs. They had to have had 3 or more prior lines of therapy, or less than that, if they were double refractory. As far as previous data from this study, the original publication demonstrated a 98% overall response rate [ORR]. Most of those responses were complete responses [CRs], and most of those CRs were minimal residual disease [MRD]–negative with longer follow-up.
We established a median PFS from this study of nearly 3 years now. To put that into some perspective, the LocoMMotion study was a prospective registry trial that evaluated expected outcomes in the modern era in this similar group of patients who were triple class exposed to 3 or more prior lines of therapy. In that registry study, the median PFS was only 4.6 months. To achieve a median PFS of 36 months is really quite remarkable. With this long-term follow-up, what we really wanted to [identify] for those patients who are still responding was how durable those responses are, and what the median OS looks like at this time.
What were the baseline patient characteristics?
Regarding the baseline characteristics, patients had triple class–exposed multiple myeloma and had previous exposure to CD38 antibodies, PIs, and IMiDs. They had to have had 3 or more prior lines of therapy or be double refractory to an IMiD and a PI. This was a single-arm study. Patients [underwent] leukapheresis and then went on to receive cilta-cel infusion after 3 days of lymphodepleting chemotherapy with fludarabine and cyclophosphamide. For this long-term follow-up [analysis], patients on this particular CARTITUDE program segued into this CARTITUDE study to track durability of PFS, and, just as importantly, OS, and any long-term potential adverse effects [AEs] that we might see.
What were the key efficacy findings?
Ninety-seven patients were treated with cilta-cel in this particular study. Remarkably, at 5 years and beyond, 33% of those 97 patients are still alive and progression-free. In one of the centers that enrolled a particularly high number of patients, they were doing annual MRD assessments and PET/CTs on their patients who had achieved a stringent CR [sCR]. Of these 12 patients, all of them were MRD-negative at 5 years and beyond and in a complete metabolic response by PET/CT. This raises the question as to whether some of these patients may be cured after a single infusion of cilta-cel. Whether you want to use the word cure or not, everyone would be very comfortable in saying that these are unprecedented remissions.
Was there anything to note about the safety profile of cilta-cel with the long-term follow-up?
Fortunately, there were no new safety signals observed in this particular study with long-term follow-up. We observed no new cases of the movement and neurocognitive toxicities that had been seen previously [with cilta-cel]. This is a Parkinson-like AE that is of concern. We did not see any new cases of cranial nerve palsies or demyelinating polyneuropathies. There were no new cases of secondary hematologic malignancies such as myelodysplastic syndrome, acute myeloid leukemia, or CAR T-cell lymphomas. There were 2 additional secondary primary malignancies seen: one adenocarcinoma of the lung and one squamous cell carcinoma of the anus. [These] were felt not to be cilta-cel–related. There were several higher-grade infections that were seen, [although] none were attributed to cilta-cel.
What are the implications of these data for the use of cilta-cel clinical practice?
The data speak for themselves as far as achieving an unprecedented durability of remission in this patient population. What was exciting about this study was that, from a correlative perspective, when we evaluated the CAR T-cell [therapy] itself, there was an increased proportion of naive T cells in the product of the patients who had more durable remissions. When we [assessed this] post–cilta-cel infusion, [there was] a higher effector-to-target ratio; this was associated with better outcomes. Interestingly, the expansion of central memory T cells looks to be associated with these longer remissions, which does seem to make some biologic sense. That’s exciting because we would imagine and expect that the T cell fitness of patients who have been less heavily pretreated is going to be better [than those who were heavily pretreated.] Not only that, but we can more effectively control the effector-to-target ratio, and we can [decrease] the burden of target with more effective therapy in earlier lines of therapy.
[Overall,] the initial data from the CARTITUDE-4 study [NCT04181827], a randomized study that evaluated cilta-cel vs the standard of care for patients who had 1 to 3 prior lines of therapy, [showed] remarkable PFS curves, particularly in the standard-risk patient population. Also, CARTITUDE-5 [NCT04923893] and CARTITUDE-6 [NCT05257083] are randomized phase 3 studies investigating cilta-cel in newly diagnosed patients who are either transplant ineligible or eligible, respectively. We’ll see if we’re achieving long-term remissions and possibly more cures when we’re using cilta-cel.
References
- Jagannath S, Martin TG, Lin Y, et al. Long-term (≥5-year) remission and survival after treatment with ciltacelcabtagene autoleucel in CARTITUDE-1 patients with relapsed/refractory multiple myeloma. J Clin Oncol. Published online June 3, 2025. doi: 10.1200/JCO-25-00760
- Carvykti is the first and only BCMA-targeted treatment approved by the U.S. FDA for patients with relapsed or refractory multiple myeloma who have received at least one prior line of therapy. News release. Johnson & Johnson. Updated April 6, 2025. Accessed July 9, 2025. https://www.jnj.com/media-center/press-releases/carvykti-is-the-first-and-only-bcma-targeted-treatment-approved-by-the-u-s-fda-for-patients-with-relapsed-or-refractory-multiple-myeloma-who-have-received-at-least-one-prior-line-of-therapy