Final results of pilot trial to evaluate anti-PD1 and 8 Gy in 1 fx for relapsed refractory multiple myeloma.

Abstract

8017 Background: Single agent Immune-Checkpoints, such as Anti-PD1, have not be successful. A pilot phase 1, 2 trial (NCT03267888) was conducted to see if radiotherapy (RT) and anti-PD1 (Pembrolizumab) could provide early signals of safety and response. Methods: Inclusion criteria included patients > 18 years of age, ECOG 0-1, able to give informed consent, have relapsed/refractory myeloma, and have ≥1 osseous and/or extra-osseous lesion that could undergo RT. Patients had to be candidates for anti-PD1 based on organ function testing, have measurable disease per International Myeloma Working Group Criteria (IMWG), and/or have progressive disease on serial staging PET/CT. IRB approval was obtained. RT (8 Gy in 1 fx) was given on day 0, cycle 1 followed by pembrolizumab (200 mg/kg iv on day 2 or 3, then every 3 weeks +/- 7 days) for 2 years or until progression. Primary endpoint was toxicity. Secondary endpoints were IMWG response, abscopal response, overall survival (OS), and immunological changes on serial blood collections. Patients were assessed at 3, 6, and 12 months for progression free survival (PFS) using IMWG and serial PET/CT scans. Patients with stable disease were continued on the trial. Patients that progressed were censored. Standard statistical analysis was performed, and included Kaplan-Meier to estimate OS and PFS. Results: From June, 2018 until October, 2021, 32 patients were screened and 25 were enrolled. Of the enrolled patients, 76% were Caucasian, 64% had ECOG 1, and the mean age was 60 years. Prior to enrollment, the median number of prior lines of therapy that a patient had filed was 5.0 (range: 2 – 11). There was no grade 2 or higher radiation related toxicity within the irradiated volume using CTCAE 4.0. Only one case of ≥ grade 3 (fevers) pembrolizumab-related toxicity was noted. Abscopal response, defined as improvement of a non-targeted lesion, was noted in 5 of 25 patients (20%). IMWG showed robust reduction in the paraproteins and other myeloma labs, suggesting response to radiotherapy and anti-PD1. A total of 8 patients showed response. Of those responding patients, 5 were post CarT cell patients, suggesting that the most benefit may be in post CarT cell patients. None of the post CarT cell patients were noted to have cytokine release syndrome and/or neurotoxicity. Of the responding patients, some of these were associated to have a robust CD 8 T cell activation. The 6 and 12 month PFS for the entire cohort was 31.8% and 22.7%, respectively. The 6 and 12-month OS for the entire cohort was 68% and 64%, respectively. Those that were post CarT, there was a higher 6 month PFS (50%) and OS (71.4%). Conclusions: Combination therapy of single-fraction, low-dose radiation therapy with pembrolizumab appears to be safe and shows early promise of efficacy in MM pts progressing following CarT therapy. Larger trials are warranted in the relapsed/refractory myeloma patients. Clinical trial information: NCT03267888 .