Successful treatment of two refractory acute lymphoblastic leukemia cases with an orelabrutinib-based regimen

Abstract Background The traditional treatment strategy for B-cell acute lymphoblastic leukemia (B-ALL) primarily relies on chemotherapy, but patient outcomes vary significantly, with some exhibiting primary resistance or a high propensity for relapse. Particularly for high-risk, refractory, and relapsed patients, treatment options are extremely limited, and the prognosis is especially poor. This study reports the efficacy of an orelabrutinib-containing regimen in two cases of refractory B-ALL. Case Reports This study describes the clinical outcomes of two refractory B-ALL patients treated with an orelabrutinib-containing regimen. Case 1: A 31-year-old male diagnosed with B-ALL positive for the E2A-PBX1 fusion gene relapsed after 4 cycles of chemotherapy. Treatment with the CD22 monoclonal antibody (Inotuzumab ozogamicin) reached a CRi (complete remission with incomplete hematologic recovery), but relapse occurred one month later. The patient then received one cycle (28 days) of orelabrutinib combined with venetoclax, achieving CR with a minimal residual disease (MRD) level of 0.8% by flow cytometry. No significant adverse effects were observed during treatment. Subsequently, blinatumomab was administered to eradicate MRD, followed by a matched sibling allogeneic hematopoietic stem cell transplant. The patient remained relapse-free during an 18-month follow-up. Case 2: A 48-year-old female diagnosed with B-ALL harboring IKZF1 deletion and SETD2 alterations showed no response to standard induction chemotherapy(VICLP). Due to financial constraints, she was unable to receive immunotherapy and was instead treated with orelabrutinib combined with venetoclax and chidamide. After one cycle, she achieved CR with an MRD level of 1.5% by flow cytometry, with no significant adverse effects observed. She is currently undergoing consolidation chemotherapy, with serial MRD monitoring showing a gradual decline. Conclusion The successful treatment of these two cases demonstrates the potential of orelabrutinib in refractory or primary resistant B-ALL patients, offering a novel therapeutic option for this high-risk population. This study supports further exploration of orelabrutinib-containing regimens in the clinical management of B-ALL.