CAR T in Myeloma: Anito-cel Challenges and Evolving Treatment Lines
Ciara Freeman, MD, PhD, discusses the challenges of incorporating anito-cel into the treatment protocol for patients with multiple myeloma.
Ciara Freeman, MD, PhD, a medical oncologist at Moffitt Cancer Center, shed light on the complexities of integrating anitocabatgene autoleucel (anito-cel) into the standard treatment paradigm for multiple myeloma in an interview with Targeted OncologyTM. While the initial excitement surrounding CAR T-cell therapies has been significant, the practical implementation in clinical practice presents several hurdles. These challenges range from patient selection and management of potential toxicities to logistical considerations within treatment centers.
Currently, the eligibility criteria for BCMA-targeted CAR T-cell therapies vary depending on the specific agent and regulatory approvals. In the United States, ciltacabatagene autoleucel (cilta-cel; Carvykti) has already secured approval for patients with relapsed or refractory multiple myeloma who have demonstrated resistance to lenalidomide (Revlimid) after at least one prior line of therapy. This positions cilta-cel as a second-line treatment option for a specific subset of patients, offering the potential for deep and durable responses.
However, the ongoing clinical trials are exploring the efficacy and safety of these therapies in different stages of the disease and in more heavily pre-treated populations. The phase 2 registrational iMMAGINE-1 study (NCT05396885) is specifically investigating anito-cel in patients with more advanced disease who have undergone multiple prior lines of therapy. Given this focus on a later-line setting, it is less likely that the results of iMMAGINE-1 will lead to an expanded indication for anito-cel in the second-line setting. Instead, if the study demonstrates a favorable benefit-risk profile, anito-cel's initial indication will likely be reserved for patients with more refractory disease who have exhausted other treatment options, including those who are triple-class exposed (refractory to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody).
This distinction underscores the importance of the ongoing iMMAGINE-3 study (NCT06413498). This trial employs a randomized design, comparing the efficacy of anito-cel against standard of care regimens in patients who have received one to three prior lines of therapy. If iMMAGINE-3 yields positive results, demonstrating a significant improvement in outcomes for patients receiving anito-cel in this earlier setting, it could pave the way for the approval of anito-cel (and potentially other BCMA-targeting CAR T-cell therapies) for use in earlier lines of therapy. This would represent a significant advancement in the treatment algorithm for multiple myeloma, offering the potential for long-term disease control earlier in the course of the illness.
As Freeman emphasizes, however, all these potential changes are contingent upon the successful completion of ongoing research and a thorough and rigorous analysis of the collected data, including response rates, progression-free survival, overall survival, and the incidence and severity of treatment-related toxicities. The ultimate goal is to identify the optimal sequencing and positioning of these innovative CAR T-cell therapies to maximize benefit for patients with multiple myeloma.
