P-220: Use of Carfilzomib regimens in patients with Multiple Myeloma refractory to CD38 antibodies: a subgroup analysis from a prospective observational study

Background Increasing use of antibodies targeting CD38 in first line (1L) for multiple myeloma (MM) has created a need for treatments for patients who are refractory to anti-CD38. This analysis describes the use of carfilzomib (K) with lenalidomide and dexamethasone (KRd) or with dexamethasone alone (Kd) in anti-CD38 refractory patients. Methods Patients with MM who received ≥ 1 K dose and an anti-CD38 in any prior line were retrieved from a prospective real-world study (NCT03091127) of 701 patients. Patients were deemed refractory if any of these criteria were met for any prior anti-CD38 treatment: the best response was stable or progressive disease; progression was the reason for discontinuation; date of relapse was after the start date and within 60 days after the last anti-CD38 dose. Results Of patients who had previously received anti-CD38 (daratumumab [D] or isatuximab), 33 KRd and 71 Kd patients were anti-CD38 refractory at K initiation. Most received D (97% of KRd and 96% of Kd patients), mainly in the immediate prior line. Patients were heavily pre-treated, with 3 and 4 median prior lines in KRd and Kd groups, respectively. Among KRd patients who were refractory to anti-CD38 in any prior line, 18% received anti-CD38 as maintenance therapy. Anti-CD38 was given as continuous therapy in 85% of KRd and all Kd patients, of whom 33% and 52% received it as monotherapy, respectively. The most common anti-CD38 combinations received in any prior line were triplets: D and a proteasome inhibitor (PI), bortezomib or ixazomib (33%) for KRd patients; DRd (41%) for Kd patients. At K initiation, 64% and 45% of KRd and Kd patients who were anti-CD38-refractory were also refractory to PI or IMiD (including 15% and 18% to lenalidomide), respectively, and 3% and 6% of patients were refractory to a PI and IMiD. All results are from anti-CD38 refractory patients who received KRd and Kd, respectively. In those who had a disease response assessment, overall response rates (ORRs) were 67% (18/27) and 52% (32/62), and 44% and 27% had a very good partial response or better (VGPR+). At 2L or 3L (2L/3L), ORR was 75% (9/12) and 67% (6/9), with 67% and 44% of patients achieving a VGPR+. At 4L+, ORR was 60% (9/15) and 49% (26/53), while 27% and 25% had a VGPR+. The median time to K discontinuation, most commonly due to disease progression, was 7 months overall (2L/3L: 12 months; 4L+: 4 months) in KRd and 5 months overall (2L/3L: 5 months; 4L+: 5 months) in Kd patients. Treatment-related adverse events occurred in 33% and 24% of patients, of which 6% and 10% led to K discontinuation. Conclusions These results expand on initial reports (Ghandi et al. Leukemia 2019) indicating K-based regimens are suitable treatment options for anti-CD38 refractory patients, providing evidence for the use of KRd and Kd from 2L with a consistent safety profile to previous studies. Patients completing 1L anti-CD38 therapy will continue to provide further real-world results.