Dose-Dense Mini-Hyper-CVD, Inotuzumab Ozogamicin, and Blinatumomab Shows Safety, Efficacy Among Patients With Philadelphia Chromosome-Negative B-Cell ALL

Retrospective Analysis Findings

A dose-dense delivery of mini-hyper fractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine (mini-hyper-CVD), inotuzumab ozogamicin, and blinatumomab yields rapid and deep measurable residual disease (MRD)-negativity and as well as safety among patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (ALL), according to a retrospective analysis published in Clinical Lymphoma, Myeloma & Leukemia. 

Nicholas J Short, MD, The University of Texas MD Anderson Cancer Center, Houston, Texas, and coauthors explain that prior research shows that “the combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL.” 

In the present study, Short et al aimed to evaluate the potential efficacy of earlier, dose-dense delivery of blinatumomab in achieving earlier and deeper MRD responses and more beneficial outcomes. 

A total of 21 patients with B-cell ALL were included in this study. Among the 9 patients in the frontline cohort, all patients achieved complete remission (CR) or complete remission with incomplete recovery (CRi), as well as MRD negativity by flow cytometry at the end of the first cycle. In both the frontline and MRD consolidation cohorts, 91% of patients (n = 10) achieved next-generation sequencing MRD negativity at a sensitivity of 10–6. This included 60% of evaluable patients (n = 6) who achieved next-generation sequencing MRD negativity after the first cycle. 

In the relapsed/refractory cohort, the CR/CRi rate was 63%, with all responders achieving MRD negativity by flow cytometry after the first cycle. In the combined cohort of frontline and MRD-positive patients, the 1-year overall survival rate was 83%. The study authors noted that there were no novel safety signals observed in patients taking this regimen. 

Short and the study authors concluded, “Dose-dense delivery of mini-hyper-CVD, [inotuzumab ozogamicin], and blinatumomab was safe and resulted in rapid and deep MRD negativity in patients with B-cell ALL.”

“This regimen is now being prospectively evaluated in both the frontline and relapsed/refractory settings,” they added. 

Source: 

Short NJ, Jabbour E, Jamison T, et al. Dose-dense mini-hyper-CVD, inotuzumab ozogamicin and blinatumomab achieves rapid MRD-negativity in Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia. Clin Lymph Myel & Leuk. Published online: December 29, 2023. doi: 10.1016/j.clml.2023.12.016