High Response Rates and Transition to Transplant after Novel Targeted and Cellular Therapies in Adults with Relapsed/Refractory Acute Lymphoblastic Leukemia with Philadelphia-Like Fusions.

Philadelphia (Ph)-like acute lymphoblastic leukemia (ALL) is associated with poor response to standard chemotherapy. However, outcomes with novel antibody and cellular therapies in relapsed/refractory (r/r) Ph-like ALL are largely unknown. We conducted a single-center retrospective analysis of adult patients (n= 96) with r/r B-ALL with fusions associated with Ph-like who received novel salvage therapies. Patients were treated with 149 individual novel regimens [blinatumomab= 83, inotuzumab ozogamicin (InO)= 36 and CD19CAR T cells = 30]. The median age at first novel salvage therapy was 36 years (range; 18-71). Ph-like fusions were IGH::CRLF2 (n= 48), P2RY8::CRLF2 (n= 26), JAK2 (n= 9), ABL-class (n= 8), EPOR::IGH (n= 4) and ETV6::NTRK2 (n= 1). CD19CAR T cells were administered later in the course of therapy compared to blinatumomab and InO (P<0.001) and more frequently in recipients who relapsed after allogeneic hematopoietic cell transplantation (alloHCT) (P=0.002). Blinatumomab was administered at older age compared to InO and CAR T-cells (P=0.004). The complete remission (CR)/CR with incomplete hematologic recovery (CRi) rates were 63%, 72%, and 90% following blinatumomab, InO and CD19CAR, respectively, among which 50%, 50%, and 44% of responders underwent consolidation with alloHCT, respectively. In multivariable analysis, the type of novel therapy (P= 0.044) and pretreatment marrow blasts (P=0.006) predicted CR/CRi rate, while Ph-like fusion subtype (P= 0.016), pretreatment marrow blasts (P=0.022) and post response consolidation with alloHCT (P< 0.001) influenced event-free survival. In conclusion, novel therapies are effective in inducing high remission rates in patients with r/r Ph-like ALL and successfully transitioning the responders to alloHCT. This article is protected by copyright. All rights reserved.