Differences in response to immunotherapy drugs including blinatumomab and inotuzumab ozogamicin in B-ALL patients

The treatment of B-cell precursor acute lymphoblastic leukemia (B-ALL) has undoubtedly transitioned into the immunotherapy era. We conducted a retrospective study on B-ALL immunotherapy, especially regimens including blinatumomab (Blina) and inotuzumab ozogamicin (InO), at our center. A total of 21 B-ALL patients were involved in this study, including 18 with newly diagnosed (ND) B-ALL and 3 with relapsed B-ALL. RNA sequencing identified a total of five new fusions (ADD1::JAK2, PVT1::IGLL5, PAX5::KANK2, ETV6::BCL2L14, and CDKN2A::TGFBR3) in five different patients. All ND patients can be divided into four groups according to treatment response. Group 1, which included patients with PAX5::KANK2 and CREBBP::ZNF384, responded best to Blina. Group 2, which included one patient with CDKN2A::TGFBR3 fusion and one who was BCR::ABL positive, showed an inferior response to Blina compared with Group 1. Group 3 initially showed no response but subsequently responded very favorably to InO and showed further improvement with Blina. Group 4, which included patients with PVT1::IGLL5 fusion, had the poorest prognosis. In conclusion, Blina and InO showed specific treatment advantages for different patient groups in our cohort that may be attributed to intrinsic genetic characteristics, such as new fusion genes.