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

ABSTRACT 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/m 2 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.