Induction therapy with inotuzumab ozogamicin followed by conventional chemotherapy has shown promise in older patients with acute lymphoblastic leukemia (ALL), according to study findings presented by Matthias Stelljes, MD, University of Muenster, Germany, at the virtual 62nd American Society of Hematology (ASH) Annual Meeting and Exposition.

“Due to increased toxicity and infection rates in older patients, dose intensification of induction treatment often is no justifiable option. Consequently, new treatment options are needed to improve the survival of older ALL patients,” explained Dr Stelljes and colleagues.

With this in mind, the researchers conducted an open-label, phase 2 clinical trial of the German Multicenter Study Group on ALL, including patients aged 55 years or older with newly diagnosed acute B-cell ALL. 

The first induction cycle consisted of inotuzumab ozogamicin 0.8 mg/m² on day 1, 0.5 mg/m² on days 8 and 15 together with dexamethasone 10mg/m2 (days7-8, days 14-17), and 1 intrathecal injection of methotrexate, cytarabine, and dexamethasone.

The second and third induction cycle lowered the inotuzumab ozogamicin dosage to 0/.5 mg/m² on days 1,8, and 15, plus an intrathecal injection of methotrexate, cytarabine, and dexamethasone. Responses underwent evaluation after each scheduled cycle.

The primary endpoint was event-free survival (EFS) at 12-months follow-up; events included: persisting bone marrow blasts after 2 cycles of inotuzumab ozogamicin, relapse, or death. An event rate of less than or equal to 40% at the time of follow-up is considered very promising for additional testing. 

The study included 31 patients, with induction results available for 29 of them (median age, 64 years). Of the 29 patients, 25 were diagnosed with a common, 4 with pro-B lymphoblastic leukemia.
The media CD22 expression on leukemic blasts was 70% (range 21-99%)

Due to possible therapy-related liver toxicities, 1 patient received just 1 induction cycle, another received 2 induction cycles, however, both were in remission after the 1st induction. Furthermore, minimal residual disease (MRD) results measured by PCR were available for 23 patients, with 18 being MRD-negative after first induction.

At the median follow-up of 242 days, the probability of overall survival (OS) at 1 year was 82.4%, while 2 patients received an allogeneic stem cell transplantation in ongoing first remission. 4 events have occurred so far, 2 were deaths in remission, 1 relapsed ALL in the first year of treatment, and 1 relapsed disease in the second year.

The most common adverse events (AEs) during induction therapy 1, 2, and 3 were leukocytopenia (in 64%, 33% and 13% of all cases, respectively), anemia (54%, 28%, 13%), thrombocytopenia (68%, 17%, 26%), and elevation of liver enzymes (31%, 22%, 20%).

“Replacement of conventional induction chemotherapy by inotuzumab ozogamicin is feasible, results in promising remission rates, and may reduce the risk of early morbidity and lethality, particular in older patients with acute B-cell ALL,” concluded Dr Stelljes et al.—Alexandra Graziano

Stelljes M, Raffel S, Wäsch R, et al. First Results of an Open-Label Phase II Study to Evaluate the Efficacy and Safety of Inotuzumab Ozogamicin for Induction Therapy Followed By a Conventional Chemotherapy Based Consolidation and Maintenance Therapy in Patients Aged 56 Years and Older with Acute Lymphoblastic Leukemia (INITIAL-1 trial). Presented at: the 62nd ASH Annual Meeting and Exposition; December 5-8, 2020; virtual. Abstract 267.