CAR T-cell Therapy Cilta-cel Continues to Show Benefits in Heavily Treated Myeloma Patients

Ciltacabtagene autoleucel, an investigational CAR T-cell therapy for multiple myeloma, continues to lead to deep and durable responses in heavily treated patients with relapsed or refractory disease, new data from the CARTITUDE-1 clinical trial show.

The findings were shared recently in the oral presentation, “Phase 1b/2 Study of Ciltacabtagene Autoleucel, a B-Cell Maturation Antigen–Directed Chimeric Antigen Receptor T Cell Therapy, in Relapsed/Refractory Multiple Myeloma,” at the American Society of Hematology (ASH) 2020 Annual Meeting and Exposition, held virtually Dec. 5–8.

“In the CARTITUDE-1 study, heavily pretreated patients, including those who were triple-class refractory, achieved an impressive response following a single infusion of ciltacabtagene autoleucel,” Deepu Madduri, MD, an assistant professor at The Tisch Cancer Institute at Mount Sinai, New York, and the study’s principal investigator, said in a press release.

Ciltacabtagene autoleucel (cilta-cel) is a form of immunotherapy in which an individual’s own T-cells — immune cells with the ability to kill cancer cells — are collected and engineered in a lab to make them better at finding and killing cancer cells.

Specifically, cilta-cel contains modified T-cells designed to kill cells that express the B-cell mature antigen (BCMA), a protein found at high levels on the surface of myeloma cells. The modified cells are expanded to several millions and then infused back into the patient.

The therapy is being developed by Legend Biotech and Janssen. It also is known as LCAR-B38M in China and as JNJ-4528 outside of China.

The ongoing CARTITUDE-1 Phase 1b/2 clinical trial (NCT03548207), sponsored by Janssen, is exploring cilta-cel for the treatment of relapsed or refractory myeloma patients. Participants must have received at least three lines of prior treatment — including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and a CD38 inhibitor — or failed to respond to treatment with a PI and an IMiD.

The trial is being conducted in two parts: the first part, results of which were announced previously, aimed to identify the best dosage of cilta-cel for patients. The second part intends to determine the effectiveness of the optimal dose selected during the initial part of the study.

At the time of the analysis, a total of 97 patients had entered the trial, including 29 in the first part and 68 in Phase 2.

Participants in the trial had received a median of six prior lines of therapy, with some having received up to 18 previous treatment lines. Nearly all participants (99%) had failed to respond to their last line of treatment (refractory), and most (88%) were refractory to three classes of therapy (triple-refractory).

Over a median follow-up of 12.4 months, nearly all patients (97%) experienced a reduction in cancer burden, with 67% achieving deep complete responses (no detectable cancer). Responses were ongoing in 72% of patients.

The median time to first response was one month, while patients required a median of 1.8 months to achieve a complete response. The researchers noted that responses tended to deepen (improve) over time.

Among the 53 patients evaluable for analysis, 93% were negative for minimum residual disease, meaning they had less than one malignant cancer cell per 10,000 white blood cells.

At one year, 77% of patients in the trial were alive and without signs of disease worsening, and 89% remained alive. Since more than half of patients were alive and had not progressed, median values for these measurements could not be estimated. The median duration of response, similarly, has not been reached.

The most common adverse events (side effects) in CARTITUDE-1 were low levels of blood cells, including neutrophils, platelets, red blood cells, leukocytes, and lymphocytes.

Cytokine release syndrome, a potentially life-threatening complication of immunotherapies, was observed in 95% of patients, but most were mild to moderate in severity resolved within two weeks. Nervous system damage of any kind occurred in 20.6% of participants.

There were 14 deaths reported during the study: five due to disease progression, three due to adverse events unrelated to treatment, and six due to adverse events related to treatment.

“We are excited to see these latest results reinforce the early promising data previously presented and hope that one day cilta-cel can offer a viable treatment option for multiple myeloma patients who have limited therapeutic options,” said Catherine Taylor, vice president, medical affairs therapeutic area strategy, Europe, Middle East and Africa, at Janssen-Cilag.