P-209: High response rates with IMiD retreatment post anti-CD38 exposure in patients with Multiple Myeloma

Background Anti-CD38 antibodies can alter myeloma pathobiology, and can potentially overcome refractoriness to IMIDs. The aim of the study was to evaluate the efficacy of re-treatment with IMiD-based therapy in patients refractory both to IMiDs and anti-CD38 antibodies. Patients and Methods The study included 38 patients who were refractory to anti-CD38-based therapy and to at least one IMiD. Overall, 26 (68%) patients had received lenalidomide, 11 (29%) pomalidomide and 1 (3%) thalidomide before anti-CD38 treatment. Results Median number of prior lines before IMiD retreatment was 4 (range 2 to 13). The patient distribution per R-ISS was: R-ISS 1: 8, R-ISS 2: 9, R-ISS 3: 4. Overall, 4 (11%) patients received lenalidomide-, 33 (86.5%) pomalidomide-, and 1 (2.5%) thalidomide-based regimens post anti-CD38. The majority of patients were treated with pomalidomide-cyclophosphamide-dexamethasone (PCD) (n=13) and pomalidomide-dexamethasone (PomD) (n=11). The remaining 14 patients were treated with other IMiD-based triplets. Importantly, 10 (26%) patients received the same IMiD as prior to anti-CD38 exposure (lenalidomide n=2, pomalidomide n=8). Median time from diagnosis to IMiD re-treatment was 61.5 months. Overall, 20 patients (53%) achieved a response during IMiD retreatment, including CR=1, VGPR=5, PR=10 and MR=4; 11 patients achieved SD, whereas 7 patients progressed. The disease control rate (DCR=SD+PR+VGPR+CR) was 82%. Among the patients re-exposed to the same IMiD, 5 responded, 3 progressed and 2 remained stable. Among the responders, 1 achieved VGPR with PCD, 2 PR with PCD and DaraPomDex, whereas 2 showed MR with PCD and PCD with Bortezomib. 79% (22/28) of the patients received pomalidomide following previous exposure to lenalidomide; among them, 15/22 (68%) patients responded (1 CR, 4 VGPR, 8 PR, 2 MR), 3 remained stable and 4 progressed. Interestingly, 10 out of 13 (77%) patients who received PCD responded. Median PFS for all patients was 4 months (range 2.9-4.8). Median time to next treatment (TtNT) for the whole study cohort as well as for those who received the same IMiD pre- and post-exposure to anti-CD38 was 4.2 months as well. Median duration of response (DoR) for the responders was 7 months. Median TtNT for those who received pomalidomide after previous exposure to lenalidomide (n=22) was 3.9 months; median DoR among the responders was 6.6 months. Median OS 5.3 range 0.5-35.5. Conclusion IMiD retreatment in patients refractory to both an IMiD and an anti-CD38 antibody can induce significant response rates, even among patients re-exposed to the same IMiD. This indicates that after anti-CD38 therapy a long lasting, probably immunomodulatory effect may be associated with some degree of re-sensitization to IMiDs. The subgroup of patients receiving PCD derived the most benefit. In this context, a prospective study evaluating the role of PCD in this population is currently ongoing.