Long‐term follow‐up of salvage therapy using a combination of inotuzumab ozogamicin and mini–hyper‐CVD with or without blinatumomab in relapsed/refractory Philadelphia chromosome–negative acute lymphoblastic leukemia

BACKGROUND The outcome of patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. The combination of inotuzumab with low‐intensity mini–hyper‐CVD (mini‐hyper‐CVD; cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m 2 × 4 doses) chemotherapy has shown encouraging results. The sequential addition of blinatumomab might improve outcome in patients with R/R ALL. METHODS We used lower intensity chemotherapy, mini‐hyper‐CVD (cyclophosphamide and dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, cytarabine at 0.5 g/m 2 x 4 doses) compared to conventional hyper‐CVAD. RESULTS Ninety‐six patients with a median age of 37 years (range, 18‐87 years) were treated. Overall, 77 patients (80%) responded, 55 (57%) of whom achieved complete response. The overall measurable residual disease negativity rate among responders was 83%. Forty‐four (46%) patients underwent later allogeneic stem cell transplantation. Veno‐occlusive disease of any grade occurred in 10 (10%) patients. The rates were 13% with the original schedule and 3% with the use of lower‐dose inotuzumab and sequential blinatumomab. With a median follow‐up of 36 months, the median overall survival (OS) was 13.4 months, with 3‐year OS rates of 33%. The 3‐year OS rate for patients with CD22 expression ≥70% and without adverse cytogenetics ( KMT2A rearrangements, low hypodiploidy/near triploidy) was 55%. CONCLUSION The combination of inotuzumab and low‐intensity mini‐hyper‐CVD chemotherapy with or without blinatumomab shows sustained efficacy in patients with R/R ALL.