February 2016, Vol. 5, No. 1
Promising Combo in Elderly Patients with ALL
Elderly patients with acute lymphoblastic leukemia (ALL) are difficult to treat. A new study suggests that frontline treatment with the combination of the investigational antibody-drug conjugate inotuzumab ozogamicin plus deintensified chemotherapy is a good option for older patients with this disease.
In a phase 2 trial, the combination had impressive results. Overall response rate (ORR) was 97%, complete cytologic response rate was 100%, and minimal residual disease (MRD) negativity was 100%. Phase 3 trials are needed to confirm these results before it can be adopted in clinical practice.
“Early results for response rates and 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 author Elias Jabbour, MD, MD Anderson Cancer Center, Houston, TX.
Inotuzumab ozogamicin 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—a modification of hyper CVAD used in younger patients with ALL. Mini-hyper-CVD has lower cyclophosphamide, dexamethasone, methotrexate, and cytarabine doses and no anthracycline.
“The combination of inotuzumab ozogamicin and mini-hyper-CVD has the potential for high efficacy and low toxicity,” Jabbour said.
The study enrolled 38 patients aged ≥60 years with newly diagnosed ALL. Median age was 69 years (the oldest patient was 79 years). Following induction therapy, 34 of 35 evaluable patients achieved a complete response (CR); ORR 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 MRD negativity.
Median time to platelet recovery was 23 days in cycle 1 and 22 days in subsequent cycles. Median time to neutrophil recovery was 16 days and 17 days, respectively.
Notable grade 3/4 adverse events included thrombocytopenia (74%), infection during consolidation (74%), infection during induction (53%), and hyperglycemia (50%). Veno-occlusive disease occurred in 4 patients (10%).
Two-year CR duration was 81%, and 2-year overall survival was 64%. At a median follow-up of 23 months, 9 patients in CR died. 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 DeAngelo, MD, Dana-Farber Cancer Institute, Boston, MA.
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