2024 Top Story in Oncology: Outcomes in Patients With Multiple Myeloma With CAR T-Cell Therapy in the Standard-of-Care Setting

Although many positive things happened for myeloma in 2024, including progress with CAR T-cell therapy and bispecific antibodies clinical trials as well as the recommendation by the Oncologic Drugs Advisory Committee to use minimal residual disease as a regulatory endpoint, I chose a real-world evidence study as the myeloma story of the year.

Dr. Sidana and colleagues reported the outcomes of 255 patients with relapsed/refractory multiple myeloma treated at academic institutions with ciltacabtagene autoleucel (cilta-cel).¹ The study was important as we wanted to have real-world evidence on the product. Populations treated in clinical trials do not necessarily reflect what happens in standard clinical practice, as they are usually healthier patients. The data by Dr. Sidana et al show remarkable similarities between clinical trials and the real world. In this study — and just like in clinical trials — a small fraction of patients were not able to be infused; but, interestingly, only a very small minority because of manufacturing failure (1%). Sometimes, patients progressed or had other complications that precluded the use of cilta-cel. The patient population treated in this report had more advanced disease as they had a median of six prior lines of therapy.

Toxicity was as expected, with cytokine release syndrome occurring in 75% of patients and immune effector cell–associated neurotoxicity syndrome (ICANS) in 14%; however, both were usually mild. They also report on delayed neurotoxicity. This delayed neurotoxicity was more common if the patient had experienced ICANS or had prior use of steroids (presumptively to treat ICANS). Overall, 5 patients developed parkinsonism, leading to an incidence rate of 2%, and only 1 patient improved. Other patients developed Bell’s palsy, and some developed peripheral neuropathy. The non-relapse mortality rate was high at 10%, mostly due to infection.

Regarding the efficacy, the overall and complete response rates among patients who were infused were 89% and 70%, respectively. However, among patients who received conforming CAR T-cell products, the response rate was higher at 94% and the complete response rate was 74%. These numbers were similar to those noted among patients in this cohort who would have been eligible for the CARTITUDE-1 clinical trial.² Among patients with conforming products, the progression-free survival rate was 72% at 12 months. Lastly, those with prior exposure to BCMA therapeutics had a median progression-free survival of 13.6 months.

Clinical experience is likely to lead to better use of CAR T cells. For instance, the treatment of patients with a lower burden of disease and more aggressive management of ICANS is hoped to be a path to reducing the risk of delayed neurotoxicity. We will see more patients who are clearly progressing but don’t have a significant tumor burden and for whom CAR T cells might even be able to be used without bridging therapy. Lastly, a more aggressive approach toward the replacement of immunoglobulins should lead to a decreased risk of serious infections. Although we don’t have all the answers, the future for CAR T-cell therapy as an essential tool in the treatment of relapsed and refractory myeloma continues to be established. The remaining questions exist, such as whether one should use cilta-cel at first relapse and whether CAR T-cell therapy will be part of induction therapy in the future.