Salvage therapy for immune-mediated bone marrow failure

Abstract Most acquired idiopathic bone marrow failure syndromes (BMFS) are thought to be cytotoxic T cell-mediated and are responsive to immunosuppressive therapies (IST) targeting T cells. However, in addition to frequent relapses, a proportion of cases remain refractory to first- and second-line agents due to a lack of clinical trials in the refractory and relapsed disease setting. Recently, the landscape of IST has expanded significantly, harnessing multiple molecular pathways that could be theoretically useful in the BMFS setting. In this manuscript, we retrospectively analyzed clinical responses to selected salvage IST, including sirolimus, tofacitinib, and subcutaneously administered abatacept and alemtuzumab, in a cohort of 151 patients with aplastic anemia, pure red cell aplasia, large granular lymphocytic leukemia, and other rare hypoproliferative BMFS. Our results indicate significant salvage rates with these agents and differential efficacy in specific clinical scenarios, showing differences in responses in affected lineages and in different disease states. We report that different modalities of IST may have lineage-restricted and overall responses in relapsed or refractory BMFS states, and durable response can be achieved in clinically difficult cases. These findings underscore the need for clinical trials to establish the safety and efficacy of alternative agents as substitute lines of therapy in BMFS.