CAR-T shows ‘promising’ efficacy for high-risk multiple myeloma

April 24, 2022

3 minute read

Source/Disclosures

Source:

Cohen AD, et al. Abstract 61. Submitted to: Tandem Meetings | Transplantation & Cell Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.

Disclosures:
Janssen and Legend Biotech funded the study. Cohen reports consulting roles or research funding from AstraZeneca, Bristol Myers Squibb/Celgene, Genentech/Roche, GSK, Janssen, Novartis, Oncopeptides and Takeda. Please see the summary for all relevant financial disclosures from other researchers.


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According to the results of a cohort analysis of the CARTITUDE-2 trial, ciltacabtagene autoleucel induced an overall response rate of 95% in patients with multiple myeloma who had an early relapse after first-line treatment.

Study data — presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR – suggest that chimeric antigen receptor T-cell therapy is safe and effective when given as early treatment for unresponsive high-risk multiple myeloma patients not standard first-line treatments, the researchers concluded.

Response rate in Cohort B.

Data derived from Cohen AD, et al. Abstract 61. Submitted to: Tandem Meetings | Transplantation & Cell Therapy Meetings of ASTCT and CIBMTR; April 23-26, 2022; Salt Lake City.

Background

Ciltacabtagene autoleucel (Carvykti; Janssen, Legend Biotech), also known as cilta-cel, is currently approved for use in patients with relapsed or refractory multiple myeloma after four prior lines of treatment.

Patients treated in the CARTITUDE-1 trial that led to the approval of cilta-cel had received an average of six prior lines of therapy. The rationale for moving cilta-cel into earlier treatment lines comes from the assumption that using more adapted T cells with less exposure to toxic therapy would lead to more effective CAR-T products, according to Adam D. Cohen, MD, associate professor of medicine at the University of Pennsylvania Perelman School of Medicine, director of myeloma immunotherapy at the Abramson Cancer Center, and one of the study’s principal investigators.

Adam D. Cohen, MD

Adam D. Cohen

“These are patients with highly refractory disease and weakened immune systems,” he told Healio. “Yes [cilta-cel] is effective as a later therapy using T cells from a heavily pretreated patient, we hypothesized that it might be as effective, or even more so, if given as an earlier line of treatment.

Other factors, such as manufacturing delays since the therapy was approved for commercial use, motivated researchers to evaluate cilta-cel in first-line therapy, Cohen said. The researchers hope that delivering the therapy sooner will lead to the accumulation of less advanced disease and fewer patients dying while waiting for their CAR T cells to be made.

More importantly, earlier therapy may be a more effective option for people in the high-risk early relapse subgroup that Cohen and his colleagues are evaluating.

“It’s a group that historically has done very poorly,” he said. “Even though many options are available, these patients tend to follow therapies quickly and survive poorly.”

Methodology

Cohen and colleagues performed a subset analysis of Cohort B of the multicenter Phase 2 CARTITUDE-2 trial of cilta-cel – an autologous B-cell maturation antigen-directed CAR T-cell therapy ( BCMA) – for patients with multiple myeloma. They designed the study to assess the safety and efficacy of cilta-cel as an early treatment, with cohort B consisting of patients with early relapse after first-line treatment with a protease inhibitor and a drug immunomodulatory imide.

The cohort included 19 patients (median age, 58 years; range, 44-67; 74% male) who experienced disease progression within 12 months of autologous hematopoietic stem transplantation (HSCT) or treatment with first line and who had not received prior CAR-T therapy. or BCMA-led therapies.

Study participants received lymphodepleting pretreatment chemotherapy followed by a single infusion of cilta-cel at a target dose of 0.75 × 106 CAR T cells/kg.

The median follow-up was 10.6 months (range, 4.1-17.4), with a data cut-off date of October 31, 2021.

Main findings

Treatment with cilta-cel produced an overall response rate of 95% (95% CI, 74-99.9) in Cohort B patients. Seventy-nine percent (95% CI, 54 .4-93.9) had a complete treatment response or better, including 26% with a complete response and 53% with a rigorous complete response.

The researchers observed a median time to first response of 1 month (range, 0.9-2.6) after cilta-cel infusion, with a median time to best response of 2.5 months (range, 0.9-11 ,8).

Further analysis showed a 6-month PFS of 90% (95% CI, 64.1-97.3) and a 12-month PFS of 84% (95% CI, 57.9-94.5 ).

The median duration of response had not been reached.

The most common treatment-related adverse events were haematological in nature. Eighty-four percent of patients had grade 3 or 4 neutropenia and 47% had grade 3 or 4 anemia.

Most patients experienced cytokine release syndrome after cilta-cel infusion, but only one patient subsequently developed CRS grade 4.

Neurotoxicity occurred in 26% of patients after infusion, with one patient developing high-grade neurotoxicity. One patient in the cohort developed a treatment-related immune effector cell-associated neurotoxicity syndrome.

No treatment-related patient deaths occurred.

Clinical implications

The small number of patients and brief follow-up make it difficult to draw conclusions about the safety and effectiveness of cilta-cel as an early treatment, Cohen said.

“The results are promising, but they are not yet definitive,” he told Healio. “We need longer follow-up to see how durable these remissions will be and how they compare to currently available treatments.”

Cilta-cel has the potential to be part of a curative strategy for some patients with multiple myeloma, and is the first step in determining whether providing it earlier is not only effective, but safe for patients, Cohen added. .

“That’s why we’re doing these early studies, to make sure it won’t cause any unusual side effects that will prevent us from giving it to more patients early on,” Cohen said. “We may have the tools to cure a large percentage of multiple myeloma patients; we just have to figure out how to put them all together.

Sara H. Byrd