Hyper-CVAD and Sequential Blinatumomab Without and With Inotuzumab in Young Adults With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia.

Adding inotuzumab ozogamicin (InO) to hyper-CVAD and blinatumomab may improve outcomes in newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (B-ALL). Patients with newly diagnosed B-ALL received up to four cycles of hyper-CVAD followed by four cycles of blinatumomab. Beginning with patient #39, InO 0.3 mg/m2 was added on Days 1 and 8 to two cycles of high-dose methotrexate and cytarabine, and two cycles of blinatumomab. The primary endpoint was the relapse-free survival (RFS) rate. Seventy-five patients were treated (median age of 33 years; range, 18-59), of whom 37 (49%) received hyper-CVAD with blinatumomab and InO (cohort 2). Measurable residual disease (MRD) negativity by next-generation sequencing (sensitivity: 1 × 10-6) was achieved in 79% of patients in cohort 2. The median follow-up was 44 months (range, 13-90) overall, and 26 months (range, 8-39) in cohort 2. For the entire cohort, the estimated 3-year RFS rate was 82% and the 3-year overall survival rate was 90%. These rates were 90% versus 74% (p = 0.06) and 100% versus 82% (p = 0.01) in patients who did or did not receive InO, respectively. No sinusoidal obstruction syndrome was observed. In summary, hyper-CVAD with blinatumomab and InO improved the outcomes of patients with newly diagnosed B-ALL.