BCMA-directed CART therapy in patients with multiple myeloma and CNS involvement.

Mahmoud R. Gaballa The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Mahmoud R. Gaballa, Omar Alexis Castaneda Puglianini, Adam D. Cohen, Dan T. Vogl, Alfred Chung, Christopher J. Ferreri, Peter M. Voorhees, Doris K. Hansen, Krina K. Patel

Authors Mahmoud R. Gaballa The University of Texas MD Anderson Cancer Center, Houston, TX info_outline Mahmoud R. Gaballa, Omar Alexis Castaneda Puglianini, Adam D. Cohen, Dan T. Vogl, Alfred Chung, Christopher J. Ferreri, Peter M. Voorhees, Doris K. Hansen, Krina K. Patel Organizations The University of Texas MD Anderson Cancer Center, Houston, TX, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, University of Pennsylvania, Philadelphia, PA, Hospital of the University of Pennsylvania, Philadelphia, PA, University of California, San Francisco, San Francisco, CA, Levine Cancer Institute, Charlotte, NC Abstract Disclosures Research Funding No funding sources reported Background: CART therapy represents a breakthrough in therapy for patients (ptns) with relapsed or refractory (R/R) multiple myeloma (MM). Pts with MM who have CNS involvement are commonly excluded from clinical trials and have limited therapeutic options. We evaluated the safety and efficacy of BCMA-directed CART therapies in ptns with MM and CNS involvement. Methods: 5 US academic medical centers contributed data to this retrospective analysis. 11 ptns with MM with CNS involvement received BCMA-directed CART (7 and 4 pts received ide-cel and cilta-cel, respectively). Results: Eight (72%) ptns were male, 3 (27%) had high-risk (HR) cytogenetics, and 10 (91%) had extramedullary disease (dz). Four (36%) ptns had brain/cranial nerve dz, 1 (9%) had spine dz, and 6 (55%) had both. CNS dz was evident on MRI in 100% of ptns and on CSF in 4 ptns (36%). Five ptns (45%) had ≤60 days between CNS diagnosis and CART therapy, 3 (27%) had >300 days from CNS dz with 2 requiring CNS-directed therapy (CNS-Tx) close to CART during bridging, and 3 (27%) were diagnosed soon after CART infusion. Six (55%) ptns received CNS-Tx as part of bridging; radiotherapy (RT, 2 ptns), RT + intrathecal (IT) chemotherapy (chemo) (2 ptns), IT chemo (1 ptn), and surgery + RT (1 ptn). Five (45%) ptns didn’t receive CNS-Tx as part of bridging for the following reasons; 3 were diagnosed soon post CART and received RT post-infusion, 1 had recent chemo, and 1 was treated for CNS dz 587 days prior to CART and didn’t require CNS-Tx during bridging. Seven ptns (64%) had treated CNS dz at the time of lymphodepleting chemo. Nine (82%) ptns had grade (G) 1/2 CRS and none had G ≥3CRS. Two ptns (18%) had G1 ICANS, 1 (9%) had G3 ICANS, and none had G4 ICANS. Two ptns experienced delayed neurotoxicity post ide-cel, 1 with delayed lethargy that was treated with steroids, and the other with progressive multifocal leukoencephalopathy that was treated with steroids plus pembrolizumab. None had delayed parkinsonian side effects. With a median follow-up of 104 days post-infusion, the best responses achieved were 45% CR/sCR, 18% VGPR, 9% PR, with an overall response (ORR) of 73%. Seven ptns were evaluable for CNS responses by day 90 with a 100% CNS response rate defined by improved imaging findings or clearance of CSF involvement. CNS recurrence occurred in 1 ptn (9%) by day 172 while 5 (45%) had continued systemic response at last assessment. Conclusions: This study suggests that BCMA directed CART therapy in ptns with MM and CNS involvement is safe and feasible. Of the evaluable ptns for CNS response, 100% showed CNS response by day 90. Larger studies with longer follow up are needed to confirm these findings. Key characteristics and outcome. N=11 (%) Age, median (range) 58 (36-71) HR Cytogenetics 3 (27%) Extramedullary Dz 10 (91%) CRS G ≥3 0 ICANS G≥3 1 (9%) Delayed Neurotoxicity 2 (18%) Parkinsonian side effects 0 ORR 73% CNS Response 100%