FROM LANCET ONCOLOGY
Inotuzumab ozogamicin appeared active and safe when added to reduced-intensity chemotherapy for older patients with Philadelphia chromosome–negative acute lymphoblastic leukemia, according to the results of a single-arm phase 2 study.
After a median follow-up of 29 months, 2-year progression-free survival was 59% with a median of 25 months for 52 patients with newly diagnosed disease who were aged 60 years or older, Hagop Kantarjian, MD , and his associates reported online in the Lancet Oncology .
Nearly every patient experienced an overall response (98%). The treatment also appeared to be safe, Dr. Kantarjian and associates wrote.
They reported that no patient died within 4 weeks of treatment and that four patients experienced veno-occlusive disease. Common grade 3 or 4 side effects included thrombocytopenia (81%), consolidation chemotherapy (69%), hyperglycemia (54%), infections during induction (52%), hypokalemia (31%), increased aminotransferases (19%), hyperbilirubinemia (17%), and hemorrhage (15%). Six patients died from treatment-related side effects, five of whom died from sepsis and one of whom died as a result of veno-occlusive disease.
Inotuzumab ozogamicin is an anti-CD22 monoclonal antibody that is bound to the toxin calicheamicin. It has shown “substantial improvements” for some patient subgroups when added to hyper-CVAD chemotherapy (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and high-dose cytarabine); however, older patients have yet to experience a similar benefit, Dr. Kantarjian and his associates said.
Both CVAD and inotuzumab ozogamicin have shown to be quite toxic for older patients. So – in order limit increased toxicity – Dr. Kantarjian and his associates lowered the intensity of hyper-CVAD. They accomplished this by reducing some aspects of the regimen by up to 50% and eliminating anthracyclines altogether. The researchers referred to this regimen as “mini–hyper-CVD.” The mini–hyper-CVD did not appear to impact activity.
“In our study, activity did not appear to be compromised by the use of lower-intensity chemotherapy in combination with a novel monoclonal antibody,” they wrote.
Dr. Kantarjian and his associates noted that, while they observed fewer deaths compared with previously published data, the number of deaths they did observe in patients who achieved a complete response was high.
They suggested that modifications to the regimen could further improve safety and that such modifications required further research.
For the time being, however, the researchers noted that this low-intensity regimen, in combination in inotuzumab ozogamicin, is highly effective and that these data now require prospective confirmation in a randomized, phase 3 setting.
The study was funded by the MD Anderson Cancer Center. Researchers reported that Pfizer provided inotuzumab ozogamicin free of charge and that Dr. Kantarjian and two other researchers received grants from Pfizer.
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SOURCE: Kantarjian H et al. Lancet Oncol. 2018 Jan 15. doi: 10.1016/S1470-2945(18)30011-1 .
