In a randomized phase III study of the drug inotuzumab ozogamicin, a statistically significant percentage of patients with acute lymphoblastic leukemia (ALL) whose disease had relapsed following standard therapies, qualified for stem cell transplants after treatment with the drug.1
Inotuzumab ozogamicin is a type of drug known as an antibody-drug conjugate. It is also known as CMC-544, and it links an antibody that targets CD22, a protein found on the surface of more than 90% of ALL cells, to calicheamicin. The ALL cells draw the antibody and its drug inside, and then the calicheamicin leads to apoptosis.
Complete remission rates were nearly 81% in the inotuzumab ozogamicin treatment arm and 29.4% in the standard intensive chemotherapy arm. Progression-free survival was a median of 5.0 months with the study drug and 1.8 months with standard care (hazard ratio (HR) = 0.45; P < .001); median overall survival was 7.7 months vs 6.7 months, respectively, (HR = 0.77; P = .04).
“Forty-one percent of ALL patients in the study were able to proceed to transplant after receiving inotuzumab ozogamicin compared with the 11% we have seen qualify through standard chemotherapy,” said Hagop Kantarjian, MD, chair of leukemia at The University of Texas MD Anderson Cancer Center, Houston.
“Given that stem cell transplant is considered the only curative treatment option, the ability of inotuzumab ozogamicin to increase the number of patients able to bridge to transplant is encouraging.”
Donor stem cell transplants generally are considered curative for this aggressive form of leukemia expected to be diagnosed in more than 6500 American adults in 2016. However, patients must be in complete remission before they are eligible for transplant.
Current therapies for adults with newly diagnosed B-cell ALL result in complete remission (CR) rates of 60% to 90%. However, many of those patients will relapse and only approximately 30% to 50% will achieve long-term, disease-free survival lasting more than 3 years.
“Standard chemotherapy regimens result in complete remission in 31% to 41% of patients who relapse earlier, and just 18% to 25% in those who relapse later,” said Kantarjian. “Patients in the inotuzumab ozogamicin study had remission rates of 58%, higher than previously reported, possibly due to patients being treated later in the disease course.”
The study reported moderate side effects, the most common was cytopenia, a disorder that reduces blood cell production, and liver toxicity.
Funding for this study was provided by Pfizer Inc.
1.Kantarjian HM, DeAngelo DJ, Stellges M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia [published online June 12, 2016]. N Engl J Med. doi:10.1056/NEJMoa1509277.