In a real-world setting, standard-of-care Carvykti (ciltacabta-gene autoleucel) has been shown to elicit responses from nearly all participating patients with relapsed/ refractory multiple myeloma (R/R MM).
Carvykti is a type of chimeric antigen receptor-T (CAR-T ) cell therapy, which, as explained by the National Cancer Institute, involves a patient’s T cells — part
of the immune system — being extracted, changed in a laboratory to attack cancer cells, grown in the laboratory and infused back into the patient.
Overall and complete response rates were 89% and 70%, respectively, in
all patients who received Carvykti, 94% and 74% in 191 patients who received conforming Carvykti and 95% and 76% in 152 patients treated with conforming Carvykti with fludarabine/ cyclophosphamide lymphodepletion.
A comforming treatment is administered according to the specifications of
the FDA’s approval, and lymphodepletion is a short course of chemotherapy administered before CAR-T cell therapy.
The Food and Drug Administration (FDA) approved Carvykti in 2022 for adults with R/R MM who had received at least four prior lines of treatment. In 2024, the agency approved Carvykti for patients who received at least one prior line of therapy.
In the final analysis of the CARTITUDE-1 clinical trial, that led to the FDA’s 2022 approval of Carvykti, the overall response rate was 98%, with 83% stringent complete response, according to findings published in 2023.
The Importance of Real-World Data
Patients with R/R MM who underwent leukapheresis, or the collection of healthy white blood cells from a patient, for Carvykti manufacturing at 16 American academic medical centers were included in the study, published in Blood, with 255 patients undergoing leukapheresis and 236 receiving Carvykti.
Of the real-world patients, 54% would not have met the eligibility criteria for CARTITUDE-1.
Senior author Dr. Doris K. Hansen of Moffitt Cancer Center’s Department
of Blood and Marrow Transplant and Cellular Immunotherapy, explained in an interview with CURE why such real-world findings are significant.
“Clinical trials are invaluable because they serve as the gold standard for introducing new therapies and advancing science,” Hansen explained.
“However, clinical trials often have strict eligibility criteria. Patients must meet very specific criteria to participate — they need to have good organ function, stable blood counts and no significant comorbidities."
In contrast, Hansen said, the patients seen in day-to-day clinical practice often have a variety of health challenges, with many patients having comorbid conditions like cardiac issues or renal impairment, and with about 20% of those diagnosed with myeloma experiencing kidney problems. “Additionally,” Hansen said, “some patients may have plasma cell leukemia, amyloidosis or myeloma-related bone damage, which can lead to fractures, pain and even reduced mobility or wheelchair use. These factors often make patients ineligible for clinical trials. ... It is, therefore, very important to report on the experiences of these patients. By studying their outcomes, we can understand how treatments perform in real-world scenarios, as opposed to the controlled, ideal conditions of clinical trials.”
The eligibility criteria for CARTITUDE-1 included adequate organ function, limited comorbidities and having no prior exposure to B-cell maturation antigentargeted therapy.
Cytokine release syndrome was experienced by 75% of patients, with grade 3 (severe) or higher in 5%. Immune effector cell-associated neurotoxicity syndrome was seen in 14%, with grade 3 or higher in 4%. Delayed neurotoxicity was reported in 10% of patients.
Researchers reported a 10% nonrelapse mortality rate, mostly from infections, and noted that second primary malignancies, excluding nonmelanoma skin cancers, were seen in 5.5% of patients and myeloid malignancies/acute leukemia in 1.7%.
CAR-T cell therapy such as Carvykti, as explained by the National Cancer Institute, involves a patient’s T cells, part of the immune system, being extracted, changed in a laboratory to attack cancer cells, grown in the laboratory and infused back into the patient. Carvykti is currently approved by the FDA to be administered in the second line of treatment.
Reference
“Safety and Efficacy of Standard of Care Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma” by Dr. Surbhi Sidana, et al., Blood.
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