Elderly patients with Philadelphia-negative B-cell acute lymphoblastic leukemia (ALL) have overall poor outcomes with current therapies. Results of a new study presented at ASH 2015 suggest that frontline treatment with the investigational antibody-drug conjugate inotuzumab ozogamicin in combination with deintensified chemotherapy is a good option for older patients with this disease.
“Early results for response rates and the ability to achieve minimal residual disease negativity are better than those achieved with a chemotherapy-only approach, and this may become a new standard of care as frontline therapy for elderly ALL patients. Lower doses are being explored,” said lead investigator Elias Jabbour, MD, Associate Professor, Department of Leukemia, M.D. Anderson Cancer Center, Houston, at ASH 2015.
Inotuzumab ozogamicin is an antibody-drug conjugate that binds to CD22 on the tumor cell surface and releases potent chemotherapy into the tumor. The deintensified chemotherapy used in this trial was mini–hyper-CVD, which includes cyclophosphamide, dexamethasone at 50% dose reduction, no anthracycline, methotrexate at 75% dose reduction, and cytarabine (Cytosar-U) at 0.5 g/m2 for 4 doses. Mini–hyper-CVD has no anthracycline and has lower cyclophosphamide, dexamethasone, methotrexate, and cytarabine doses than the regimen it is modified from, which is used in younger patients with ALL.
In this phase 2 trial, the combination had impressive results. The overall response rate was 97%, the complete cytologic response rate was 100%, and minimal residual disease negativity was 100%. Phase 3 trials are needed to confirm these data before this regimen can be adopted in clinical practice.
“The combination of INO [inotuzumab ozogamicin] and mini–hyper-CVD has the potential for high efficacy and low toxicity,” Dr Jabbour said.
The study enrolled 38 patients aged ≥60 years with newly diagnosed Philadelphia-negative ALL. The median patient age was 69 years (the oldest patient was aged 79 years). After induction therapy, 34 of 35 evaluable patients achieved a complete response (CR). The overall response rate was 97%.
No deaths were reported during the first 4 weeks of induction therapy. All 19 patients with abnormal karyotype achieved a cytogenetic CR; 100% achieved minimal residual disease negativity. The median time to platelet recovery was 23 days in cycle 1, and 22 days in subsequent cycles. The median times to neutrophil recovery were 16 days and 17 days, respectively.
The 2-year CR rate was 81%, and the 2-year overall survival rate was 64%. However, at a median follow-up of 23 months, 9 patients who had a CR died.
Notable grade 3 or 4 adverse events included thrombocytopenia (74%), infection during consolidation (74%), infection during induction (53%), and hyperglycemia (50%). Veno-occlusive disease occurred in 4 (10%) patients.
Experts agree that this approach holds great promise. “The wave of the future is the combination of monoclonal antibodies plus chemotherapy. We will see extraordinary responses with this approach,” said Daniel J. DeAngelo, MD, PhD, Director, Clinical and Translational Research, Adult Leukemia Program, Dana-Farber Cancer Institute, Boston.