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Patients with relapsed/refractory myeloma who were previously treated with three or more therapies responded to an infusion of a novel CAR-T cell therapy up to 18 months with no new side effects compared with 12-month results of this study.
CAR-T cell therapy with ciltacabtagene-autoleucel (cilta-cel) may lead to long-term responses in patients with relapsed/refractory multiple myeloma.
“At a longer median follow-up of 18 months, a single dose of cilta-cel led to early, deep and durable responses in heavily pretreated patients with multiple myeloma,” said Dr. Saad Z. Usmani, chief of plasma cell disorders at Levine Cancer Institute at Atrium Health in Charlotte, North Carolina, during his presentation at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.
Researchers in this phase 1b/2 CARTITUDE-1 study evaluated cilta-cel, a novel CAR-T cell therapy, in patients with relapsed/refractory multiple myeloma who have been heavily pretreated. At a median follow-up of 12.4 months, results from this study previously demonstrated that treatment with cilta-cel led to an overall response rate (patients with partial or complete response to treatment) of 97% with a stringent complete response (disappearance of all signs of cancer and absence of molecular markers of disease) of 67%. In addition, previous follow-up data showed that patients treated with cilta-cel had an overall 12-month progression-free survival (time during or after treatment when a patient is alive without disease worsening) of 77% and an overall survival rate (time when a patient with cancer is still alive) of 89%.
In these findings presented at ASCO, researchers conducted follow-up for a median of 18 months. In particular, the primary objective of this phase 1b/2 study is to evaluate the safety and efficacy of patients with multiple myeloma who were previously treated with three or more therapies. All patients were treated with a cilta-cel infusion with a median administered dose of 0.71x106 CAR+ viable T cells/kg, although before receiving the infusion, patients underwent apheresis (procedure when blood is collected, white blood cells and platelets are removed and the blood is placed back into the patient), bridging therapy as required and lympho-depleting chemotherapy.
In total, 97 patients (median age, 61 years; 58.8% men) were treated with the cilta-cel infusion. Patients underwent a median of six prior lines of therapy. In addition, 87.6% of patients were triple-class refractory (resistant to all three classes of myeloma therapies), 42.3% were penta-drug refractory (resistance to five key myeloma drugs) and 99% of patients were refractory to their last line of therapy.
Some treatment discontinuations occurred during the study primarily related to progressive disease or death from relapsed/refractory disease, Usmani said.
During a median follow-up of 18 months, the overall response rate was 97.9% with “improvement in the deepening of response,” Usmani said. The rate of stringent complete response was 80.4%. The rate of a very good partial response (90% or greater reduction in serum monoclonal protein) or better was 94.8%. The median time to first response was one month with a median time to best response of 2.6 months. The median time to complete response or better was also 2.6 months. Additionally, the median duration of response to cilta-cel was 21.8 months, with no deaths or disease progression in 73% of patients who responded to treatment.
“The (overall response rate) benefit was seen regardless of prior drug exposure, presence of high-risk cytogenetics or extramedullary disease,” Usmani said in an interview with CURE®.
Regarding minimal residual disease (small number of cancer cells during or after treatment, defined as 10-5) negativity, 91.8% of patients with minimal residual disease evaluations (61 patients) achieved negativity within a median of one month. This rate was 57.7% for patients within the overall population. For patients who achieved a complete response or better, 89.4% were minimal residual disease evaluable and 43.3% comprised of the overall patient population.
Eighteen-month progression-free survival in all patients in this study was 66%, with a rate of 75.9% in patients with stringent complete response to treatment. In addition, overall survival at 18 months was 80.9%.
Usmani told CURE®, “No new safety concerns were observed with longer follow-up, especially with regards to neurological (side effects).”
In his presentation, he elaborated more on the side effects. “The more common all-grade as well as (severe) or (life-threatening side effects) were hematologic in nature,” Usmani said. “The nonhematologic side effects did include metabolic, (gastrointestinal) and other side effects such as fatigue, cough and (aspartate transaminase) and (alanine aminotransferase) elevations. If you look at the (severe or life-threatening side effects), we find very low percentages of (severe or life-threatening) nonhematologic (side effects).”
Usmani added that “cilta-cel has a manageable safety profile consistent with its mechanism of action.”
Of note, 92 patients had cytokine release syndrome (rapid release of cytokines into blood as a result of immunotherapy). The median time to onset of cytokine release syndrome was seven days and typically lasted for a median of four days.
“What’s important to note is of the 92 patients with (cytokine release syndrome, it) resolved within 14 days in 91 of them, and the majority of these (cytokine release syndrome) events — almost 95% — were (mild or moderate),” Usmani said.
For total CAR-T cell neurotoxicities, 20.6% of patients experienced any severity toxicities and 10.3% had a severe or worse case of neurotoxicity. No new incidence of neurotoxicity events occurred since the last time this study reported findings.
Cilta-cel is currently being investigated in ongoing trials including the phase 2 CARTITUDE-2 and phase 3 CARTITUDE-4 trials in earlier-line settings. Other results from this clinical trial program were presented at this meeting including the CARTITUDE-2 trial. Findings from this trial demonstrated that treatment with cilta-cel induced early and deep responses in a group of patients with relapsed/refractory multiple myeloma.
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