Inotuzumab Ozogamicin May Benefit Patients With Acute Lymphoblastic Leukemia

Researchers published a study June 12, 2016, in the online issue of The New England Journal of Medicine that suggests progression-free survival (PFS) and overall survival (OS) may both be longer with inotuzumab ozogamicin compared with conventional chemotherapy for acute lymphoblastic leukemia (ALL).

Inotuzumab ozogamicin (CMC-544) links an antibody that targets CD22, a protein found on the surface of more than 90% of ALL cells. Once the drug connects to CD22, the ALL cell draws it inside and dies.

Researchers conducted a randomized phase III study with inotuzumab ozogamicin in patients with ALL who had relapsed following standard therapies, but qualified for stem cell transplants. There were 326 patients who underwent randomization and the first 218 patients were included in the primary intention-to-treat analysis of complete remission.

The study showed that the rate of complete remission was significantly higher in the inotuzumab ozogamicin group (n=109) than in the standard therapy group (n=109). The difference was rather dramatic (80.7% compared to 29.4%). Among the patients who had complete remission, a higher percentage in the inotuzumab ozogamicin group had results below the threshold for minimal residual disease (0.01% marrow blasts). Again, the numbers were dramatically higher (78.4% compared to 28.1%). The study also demonstrated the duration of remission was longer in the inotuzumab ozogamicin group, with a median of 4.6 months compared to 3.1 months.

“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 study author Hagop Kantarjian, MD, Chair of Leukemia at The University of Texas MD Anderson Cancer Center, in a news release. “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.”

Current therapies for adults with newly diagnosed B-cell ALL result in complete remission rates (CR) of 60% to 90%. However, many of those patients will relapse and only about 30% to 50% will achieve long-term, disease-free survival lasting more than 3 years. Dr. Kantarjian said 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. He said patients in the inotuzumab ozogamicin study had remission rates of 58%, higher than previously reported. The study reported moderate side effects. The most common side effects were cytopenia and liver toxicity.