(PA-116) Progression Patterns by Positron Emission Tomography (PET) for Relapsed / Refractory Multiple Myeloma (RRMM) After CAR T Cell Therapy: Potential Role for Radiotherapy (RT)?

Chimeric antigen receptor (CAR) T-cell therapy has shown remarkable efficacy in MM. However, many patients (pts) have incomplete and non-durable responses. We characterized post-CAR T progression for RRMM, using PET to identify high risk lesions that may benefit from bridging RT prior to CAR T. 

Methods:

We analyzed 71 MM pts treated btw 2017-2022 with BCMA-directed CAR T (38 experimental, 33 commercial products). A total of 529 FDG-avid lesions on pre-CAR T PET (pre-apheresis if bridging therapy, pre-lymphodepleting chemotherapy if no bridging), and 321 lesions on post-CAR T PET at first failure were categorized, with failure defined as radiologic and/or serologic progression according to Lugano and International Myeloma Working Group criteria, respectively. At the pt level, we classified disease as osseous (O), extramedullary (EM) / paramedullary (PM), or mixed O and EM/PM. Individual lesions were classified as O, EM, or PM. Lesions were also classified as progressive, stable, or new at pre-CAR T PET according to SUV change from preceding PET. Failure of a lesion present on pre-CAR T PET was defined as progression involving the same anatomic structure and within 3 cm from initial lesion. Pearson’s X² test was used to compare pre- and post-CART PET. Kaplan-Meier curves for progression-free survival (PFS) were constructed.

Results:

Pre-CAR T PET was performed at median 1.4 months (range, 0.2-8.5) prior to CAR T, with 27 (39%) pts receiving systemic bridging, 10 (14%) RT +/- systemic, and 32 (46%) none. Median number of PET avid sites pre-CAR T was 6 (0-9) per pt. Of the 71 pts, 34 (53%) had mixed O and EM/PM, 24 (37%) O only, and 6 (10%) EM/PM only; 7 (10%) had no lesions. Of the 529 lesions on pre-CAR T PET, 351 (66%) were O, 131 (25%) EM, and 47 (9%) PM. A total of 61 (86%) pts progressed post-CAR T (median time to progression of 6 months (interquartile range: 2-11)), 28 (46%) of whom had first failure in new and pre-existing sites, 17 (20%) in new sites only, 6 (10%) in pre-existing sites only, and 10 (16%) serologically only. At the lesion level, 101/321 (31%) failures occurred in lesions on pre-CAR T PET. At failure, EM (44% vs 25%) and PM (12% vs 9%) lesions made up a higher percentage of all lesions compared to pre-CAR T (p< 0.001). Of the initial 529 lesions, failure occurred in 44/131 (34%) EM, 16/47 (34%) PM, and 41/351 (12%) O sites (p< 0.001). Lesions progressing at time of pre-CAR T PET failed more frequently (41/143, 29%) than those that were stable (20/130, 15%) or new (24/175, 14%) (p=0.002). PFS was worse in pts with EM disease (p< 0.001) and >3 lesions (p=0.037) pre-CART.

Conclusions:

EM and PM sites progressed locally at higher rates than O sites, as did progressive lesions pre-CAR T. PFS was worse in EM/PM sites, suggesting higher risk lesion characteristics for which targeted RT cytoreduction may be beneficial. Further analysis could inform integrating selective site RT pre-CAR T as a bridging intervention.