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CHICAGO -- A single infusion of the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel; Carvykti) reduced the risk of disease progression or death compared with standard care in lenalidomide (Revlimid)-refractory patients with multiple myeloma, the phase III randomized trial showed.

Among 419 patients who had received one to three previous therapies, the median progression-free survival (PFS) was not reached in the cilta-cel group compared with 11.8 months in the standard-care group (HR 0.26, 95% CI 0.18-0.38, P<0.001) at a median follow-up of 15.9 months, reported Binod Dhakal, MD, of the Medical College of Wisconsin in Milwaukee, during the American Society of Clinical Oncology annual meeting.

The results of the study were also published in the .

The PFS rate at 12 months was 75.9% in the cilta-cel group versus 48.6% in the standard-care group, and more patients in the B-cell maturation antigen (BCMA)-directed CAR T-cell therapy group had an overall response (84.6% vs 67.3%), a complete response or better (73.1% vs 21.8%), and an absence of minimal residual disease (60.6% vs 15.6%).

"As with other myeloma treatments, real-world translation of clinical trial results will be influenced by a variety of factors, including patient selection and fitness, patient heterogeneity, treatment accessibility and setting, and patient or physician preference," Dhakal and team wrote. "Nonetheless, the strong progression-free survival benefit and rapid and deep response with cilta-cel highlight the potential for cilta-cel to become a therapeutic option for patients with myeloma after the first relapse."

Dhakal and colleagues noted that the immunomodulator lenalidomide is recommended for newly diagnosed and relapsed or refractory multiple myeloma.

"Lenalidomide-based therapies are used extensively as frontline treatments, in both young and elderly patients and including those who are transplant-eligible and transplant-ineligible," Dhakal said. "This causes an increase in the number of cases where the disease no longer responds to lenalidomide early in the course of the disease. These findings show that cilta-cel is highly effective in patients with lenalidomide-refractory multiple myeloma as early as after first relapse."

In earlier CARTITUDE trials, cilta-cel was found to lead to early, deep, and durable responses in patients with relapsed or refractory multiple myeloma.

Commenting on the new study, Hans Lee, MD, of the University of Texas MD Anderson Cancer Center in Houston, noted that "the benefits of cilta-cel to patients with one to three prior lines of therapy who were lenalidomide-refractory over standard-of-care therapies were very impressive."

"The whole community is very excited about this," he told 口袋女优. "This study further supports moving novel therapies to earlier lines of therapy. This is where the field is definitely headed."

However, it won't happen tomorrow, he said, pointing out that the CARTITUDE-4 study represented a median 16 months of follow-up.

"It will be important to look at long-term safety from the CARTITUDE study," Lee continued. "This trial is theoretically practice-changing. But in reality, it's not practice-changing for the majority of my own patients because of the question of access to this therapy. In the next 3 to 5 years, will patients be able to get this therapy, not just at major academic medical centers, or certain countries, but across the country and across the world?"

The open-label CARTITUDE-4 trial enrolled patients with multiple myeloma across 81 sites in the U.S., Europe, Asia, and Australia who had lenalidomide resistance and had received one to three lines of therapy, including a proteasome inhibitor and an immunomodulatory drug. All patients had an Eastern Cooperative Oncology Group performance status score of 0-1.

From July 2020 to November 2021, the 419 patients were randomized 1:1 to standard care (physician's choice of pomalidomide [Pomalyst], bortezomib [Velcade], and dexamethasone [PVd] or daratumumab [Darzalex], pomalidomide, and dexamethasone [DPd]) or a single infusion of cilta-cel after the physician's choice of bridging therapy (PVd or DPd).

Median patient age was 61-62, 56-59% were men, and 74-76% were white. High-risk cytogenetic features were identified in 59.4% of patients in the cilta-cel group and 62.9% of those in the standard-care group; at least two high-risk cytogenetic abnormalities were identified in 20.7% and 23.2%, respectively.

Death from any cause was reported in 39 patients in the cilta-cel group and 46 patients in the standard-care group (HR 0.78, 95% CI 0.5-1.2).

Among the 176 patients who received cilta-cel in the as-treated population, 76.1% had cytokine release syndrome (grade 3 or 4: 1.1%; no grade 5), 4.5% had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 9.1% had cranial nerve palsy (grade 2: 8%; grade 3: 1.1%), 2.8% had CAR-T-related peripheral neuropathy (grade 1 or 2: 2.3%; grade 3: 0.6%), and one patient had movement and neurocognitive symptoms (grade 1).

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