Maintenance therapy following chimeric antigen receptor T-cell therapy in relapsed and refractory multiple myeloma: An exploratory case series evaluating feasibility and safety in a real-world setting Free

Introduction: Chimeric antigen receptor (CAR) T-cell therapy has demonstrated remarkable efficacy in patients with relapsed and refractory multiple myeloma (RRMM). However, despite achieving high-quality response, patients—particularly those who are heavily pretreated and/or have high-risk cytogenetics—remain at significant risk for disease progression, and often within 6 months to 1 year of CAR T-cell infusion. The role of maintenance therapy following CAR T-cell treatment remains underexplored. In this study, we aimed to evaluate the feasibility and safety of maintenance therapy after CAR T-cell therapy in the real-world setting.

Methods: We conducted a retrospective study on patients with RRMM who received CAR T-cell therapy followed by maintenance therapy from Aug 2021 to July 2024. Data were collected on patient demographics, disease characteristics and refractoriness, as well as details of both the CAR T-cell therapy and subsequent maintenance therapy. The safety and efficacy of maintenance therapy were evaluated utilizing common terminology criteria for adverse events (CTCAE) and international myeloma working group (IMWG) response criteria.

Results: A total of eight RRMM patients who received maintenance therapy following CAR T-cell infusion were identified. Among them, six received idecabtagene vicleucel and two received ciltacabtagene autoleucel. The median age at infusion was 64 years (range, 48–79), and five patients were male. The mean number of prior lines of therapy, excluding bridging therapy, was 5 (range 3-9). High-risk cytogenetics were present in 3/8 patients, while 7/8 were triple-class refractory and 1/8 was penta-drug refractory. Two patients received pomalidomide monotherapy, and six received an elotuzumab-based combination regimen with either pomalidomide or lenalidomide, with or without dexamethasone, as maintenance therapy. The mean time from CAR T-cell infusion to initiation of maintenance was 6 months (range, 3–12).

Following maintenance, 4/8 patients experienced deepening of response to complete response (CR) or better, as defined by MRD negativity; 3/8 had disease progression, and 1/8 maintained CR. Among those who progressed, the median time to progression from CAR T-cell infusion was 12 months (range, 10–12).

Infectious complications were common, with 7/8 patients developing respiratory infections (all Grade 2-3), including 3/8 with Grade 3 bacterial respiratory tract infections. One patient died from respiratory infection (Grade 5). Grade ≥3 neutropenia occurred in 3/8 patients, and 1/8 discontinued maintenance therapy due to non-hematologic and non-infectious toxicity.

Conclusion: Maintenance therapy following CAR T-cell infusion was associated with deepening of response in a subset of our patients (50%) with RRMM. However, the high incidence of infectious complications and hematologic toxicity highlights the need for careful patient selection and monitoring. These preliminary findings suggest that while maintenance may enhance disease control post–CAR T-cell therapy, the risk-benefit balance remains a critical consideration, and infectious complications are a particular concern. Future prospective studies are therefore warranted, including the integration and evaluation of other potent next-generation novel agents, such as cereblon E3 ligase modulators (CeLMoDs), with the potential of further enhancing the efficacy of immunotherapy in RRMM.