The implementation of 3 cycles of inotuzumab ozogamicin induction therapy as a treatment measure showed promising remission rates in patients aged >55 years with de novo acute B-lymphoblastic leukemia (B-precursor ALL), according to findings from an open label, phase 2 study.

At the 2022 ASH Annual Meeting and Exposition in New Orleans, LA, Matthias Stelljes, Prof. Dr. Med, University of Muenster, Germany, presented data from the open label, phase 2 GMALL-Initial1 trial.

Dr Stelljes and coauthors wrote, “Incorporation of novel antibody-based therapies in the first line induction therapy [for acute lymphoblastic leukemia] bears the potential of a significantly increased response rates and survival together with a reduction of treatment toxicity.”

There were 43 evaluable patients aged >55 years with recently diagnosed Ph/BCR-ABL negative B-precursor ALL (at least CD20 positivity of leukemic blasts) enrolled in this study. The median age was 64 years old (range: 56 to 80 years; ≥65 years, n = 20; ≥70 years, n = 12). Patients received 3 induction cycles of inotuzumab ozogamicin therapy. The first induction cycle included 0.8mg/m2 inotuzumab ozogamicin administered on day 1, and 0.5mg/m2 on day 8 and day 15, combined with 10 mg/m2 dexamethasone (days 7 through -8, days 14 through-17), as well as 1 intrathecal injection of methotrexate, cytarabine, and dexamethasone. The second and third induction cycles included 0.5 mg/m2 inotuzumab ozogamicin on days 1, 8, and 15, plus 1 intrathecal injection of methotrexate, cytarabine, and dexamethasone.

Patients who achieved complete remission (CR) were offered to receive 5 conventional consolidation therapies and 1 reinduction therapy in combination with rituximab and followed by a maintenance therapy with mercaptopurine (6-MP)/methotrexate. The primary endpoint of this study was event-free survival (EFS) at the 12-month follow-up point, with an event rate of ≤40% considered necessary as qualification for additional future testing of this inotuzumab ozogamicin treatment. 

Of the 43 patients, 53% and 74% were minimal residual disease (MRD) negative after the second and third induction therapy, respectively. At a median follow-up duration of 697 days, the overall survival (OS) rates at 1 and 2 years was 91% and 81% respectively. There were no deaths within the first 6 months of the study period. However, within the first year after the conclusion of the study there were 3 deaths in CR and 2 instances of relapsed ALL. This resulted in an event rate of 12% and a 1-year EFS rate of 88% (95% confidence interval [CI], 79 to 98). At 2 years, the EFS rate was 73% (95% CI, 59 to 88). Factors which are classically associated with inferior survival outcomes (age, pro-B ALL, disease burden at diagnosis, comorbidity, no MRD negative CR after induction) did not significantly impact OS or EFS in this study.

The 7 patients who exhibited persisting/reappearing MRD (n = 2) or relapse (n = 5) were treated with blinatumomab. Of the 9 patients who received an autologous stem cell transplant (aSCT), 6 of them are currently alive in CR.

During induction cycles 1, 2, and 3, the most common adverse events were leukocytopenia (in 74%, 19% and 2% respectively), anemia (37%, 5%, 0%), thrombocytopenia (49%, 7%, 2%), and elevation of liver enzymes (14%, 5%, 0%). Following second induction, 1 patient was reported with suspected veno occlusive disease.

Dr Stelljes et al concluded, as the study met the primary end point, “these promising study results could be a rationale for integrating inotuzumab ozogamicin induction therapy in future treatment recommendations,” adding, “this novel induction therapy should be evaluated in prospective randomized trials.”

Source:

Stelljes M, Alakel N, Wäsch R, et al. Inotuzumab Ozogamicin Induction Followed By Standard Chemotherapy Yields High Remission Rates and Promising Survival in Older (>55 Years) Patients with De Novo B-Lymphoblastic Leukemia (GMALL-Initial1 Trial). Presented at ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, LA. Abstract 212