P-226: Clinical outcomes of Multiple Myeloma patients after anti-CD38 monoclonal antibodies failure

Abstract

<h3>Background</h3> Anti-CD38 monoclonal antibodies (Mab) have significantly improved the prognosis of patients with multiple myeloma. However, not all patients sustain durable responses. Patients relapsed or refractory (R/R) to anti-CD38 Mab present dismal prognosis and constitute a group for whom therapeutic needs are still not defined. We aimed to describe the natural history of patients relapsed or refractory to CD38 monoclonal antibodies. <h3>Methods</h3> Unicentric retrospective analysis of 57 MM patients R/R to anti-CD38 Mab. Refractoriness was defined as progression within the first two months of treatment. We used chi-square test to compare categorical variables, the Kaplan-Meier method and log rank test for the survival analysis and multivariable analysis using logistic regression. IBM SPSS (v25.0) was used for the statistical analysis. <h3>Results</h3> The median age was 66 years, 57.9% were female. The cohort received a median of 2; R(0-11) lines of treatment previous to anti-CD38 Mab. 49% had undergone autologous transplant and 64.9% had received a proteasome inhibitor and an immunomodulatory previously. 21 patients (37%) were refractory and 20 (35%) achieved very good partial response or better response. The most frequent combinations were with lenalidomide (DRd; 11%), bortezomib (DVd; 16%), bortezomib and melphalan (D-VMP; 13%) and with carfilzomib (KDd; 27%). 26% received daratumumab in monotherapy or with corticosteroids. Median time to treatment progression was 7 months and median overall survival (OS) was 12 months for the global cohort. OS was longer in patients who achieved a deeper response (49, 12 and 4 months for patients with complete response, partial response and stable disease or progression respectively; p=0.001). High cytogenetic risk was related to poor outcomes, with an OS of 5 months and more frequent CD38 Mab refractoriness (63% vs 37% for the global cohort; p=0.007). Resistance to daratumumab as a first line treatment was observed in 8 patients. 7 of them were treated within a clinical trial for non eligible AHCT patients Median time to daratumumab progression within this group was 12 months and median OS was 49 months. 49 (86%) of the patients received at least one line of treatment after anti-CD38 Mab R/R and 47% of them had and objective response to at least one of the subsequent therapies employed, with median progression free survival (PFS) of 5 months. Daratumumab-resistant patients had longer OS when treated with regimens containing pomalidomide compared to other agents (median OS 26 vs 6 months respectively; p=0.021). <h3>Conclusion</h3> Patients R/R to CD38 targeted monoclonal antibodies present dismal prognosis, with a median OS of 12 months. Patients with high cytogenetic risk have worse outcomes, with shorter OS and higher probability to anti-CD38 Mab refractoriness. Treatment with pomalidomide-based regimens may be an interesting option for this population. The authors declare no conflicts of interest.