Dr Voorhees on Cilta-cel's Durability in Myeloma and Future Directions
Peter Voorhees, MD, hematologist-oncologist at Atrium Health Levine Cancer Institute and professor of cancer medicine at Wake Forest University School of Medicine, discusses long-term follow-up from the CARTITUDE-1 study in an interview with Targeted OncologyTM.
The CARTITUDE-1 study investigated ciltacabtagene autoleucel (cilta-cel; Carvykti) as a treatment for patients with heavily pretreated relapsed/refractory multiple myeloma (RRMM). With a median follow-up of over 5 years (61.3 months), the study showed a remarkable median overall survival of 60.7 months.
Significantly, one-third of patients (32 of 97) remained alive and progression free for at least 5 years after a single cilta-cel infusion, without needing maintenance treatment. Among a subset of these long-term responders, all achieved minimal residual disease (MRD)-negativity and negative imaging results 5 years post-treatment, suggesting deep and durable responses.
While baseline characteristics generally didn't predict long-term remission, trends suggested that lower tumor burden, specific T-cell characteristics, and higher hemoglobin/platelet counts might be associated with achieving 5-year progression-free status. The safety profile of cilta-cel remained consistent with prior findings. These results offer the first evidence that cilta-cel could be potentially curative for some RRMM patients.
According to Voorhees, the data clearly demonstrate the unprecedented durability of remission achieved with cilta-cel in this patient population. A particularly exciting aspect of the study lies in its correlative findings.
Analysis of the CAR T-cell product revealed that a higher proportion of naive T-cells was associated with more durable remissions. Furthermore, postinfusion, a higher effector-to-target ratio correlated with improved outcomes. Interestingly, the expansion of central memory T-cells also appeared linked to these longer remissions, which makes biological sense.
These findings are promising because clinicians anticipate that patients who are less heavily pretreated will have better T-cell fitness. This also suggests clinicians can more effectively manage the effector-to-target ratio by reducing the tumor burden with earlier, more potent therapies.
Initial data from CARTITUDE-4, a randomized study comparing cilta-cel to standard of care in patients with 1 to 3 prior lines of therapy, showed remarkable progression-free survival curves, especially in the standard-risk patient group. Looking ahead, CARTITUDE-5 and CARTITUDE-6 are randomized phase 3 studies investigating cilta-cel in newly diagnosed patients, both transplant-ineligible and eligible, respectively. The medical communicty is eager to see if using cilta-cel in these earlier treatment lines will lead to even longer remissions and potentially more cures.
