Evaluation of immune checkpoint inhibitors and concurrent radiation therapy for the treatment of extramedullary multiple myeloma.

e19549 Background: The prognosis of patients with extramedullary myeloma (EMM) is poor, and the median overall survival of patients who experience an extramedullary relapse is <6 months. Clinical trials include only a small subset of patients with EMM, and recently approved T-cell engagers and CAR-T cells show inferior outcomes in this patient population. Radiation therapy has important effects on the immune system and has been shown to shift the balance from tumor immune evasion toward tumor control. Preclinical evidence indicates that radiation therapy increases response rates and long-term survival of anti-PD-1 treatment by stimulating the accumulation and activation of CD8+ cytotoxic lymphocytes in the tumor microenvironment. The combination of checkpoint inhibition(CKPi) with radiation (RT) therapy has been used successfully in many cancers including melanoma, lung cancer and lymphoma. We believe that the radiation followed by CKPi with either nivolumab or pembrolizumab can induce durable responses and perhaps result in an abscopal effect with improvement of other sites of systemic disease. Methods: Following IRB approval, we conducted a retrospective chart review of EMM patients treated at Hackensack University Medical Center and John Theurer Cancer Center from 01/01/2016 to 12/31/2024. Patients who were diagnosed with EMM, received nivolumab or pembrolizumab, with concurrent RT, were included. Results: We identified 23 EMM patients who received CKPi with concurrent RT, of whom 20 were included in the analysis (14 males [70.0%], 6 females [30.0%]; median age at diagnosis: 60 years). Among these, 9 patients received nivolumab with RT, and 11 received pembrolizumab with RT. Patients received a median of 7 lines of therapies prior to CKPi with RT, with the majority having triple- or penta-refractory disease. Among the 20 patients, 10 received pomalidomide in addition to the CKPi and RT, 4 received lenalidomide, 1 received thalidomide, and 5 patients received CKPi with RT alone. Among the 20 patients, the overall response rate (ORR) was 50.0% (1 complete response [CR], 7 partial responses [PR], 2 minimal responses [MR], 7 stable/progressive disease [SD/PD], and 3 unknown). Median progression-free survival (PFS) was 3 months (95% CI: 2.0–4.0), median overall survival (OS) was 8.5 months (95% CI: 4.0–15.0). Conclusions: The combination of ICIs with RT shows a trend toward superior outcomes compared to historical controls of patients with relapsed EMM. These findings underscore the need for larger studies to further evaluate the potential benefits of this combination therapy in EMM.