Following treatment with the monoclonal antibody inotuzumab ozogamicin, a large number of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL) proceeded to stem cell transplantation.

The treatment, which was tested in an open-label, randomized phase 3 trial, was associated with better survival outcomes than those of standard care, including higher rates of complete remission, longer duration of remission, improved progression-free survival (PFS), and improved overall survival (OS), in contrast to standard chemotherapy.1

Lead author Hagop M. Kantarjian, MD, chair of leukemia at MD Anderson Cancer Center, said that 41% of patients assigned to inotuzumab ozogamicin proceeded to transplantation after treatment, in contrast with just 11% for those assigned to standard therapy (P < .001).

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“It’s a big deal in the setting of ALL treatment,” Dr Kantarjian said in an interview with Cancer Therapy Advisor. “Inotuzumab, blinatumomab, and other monoclonal and chimeric antigen receptor (CAR) T cell therapies are going to revolutionize the treatment of ALL and significantly improve the cure rate in adult ALL.”

Complete remission is often a prerequisite for subsequent allogeneic stem-cell transplantation, which is currently the only potentially curative treatment for ALL. The low rates of complete remission currently associated with chemotherapy, however, preclude more than 5% to 30% of patients proceeding to transplantation.

Dr Kantarjian and colleagues randomly assigned patients in 18 countries to inotuzumab ozogamicin (141 patients) or the investigator’s choice of standard therapy (138 patients). There was no crossover between the 2 groups.

The rate of complete remission or complete remission with incomplete hematologic recovery was 80.7% (95% CI, 72.1-87.7) in the inotuzumab ozogamicin group, versus 29.4% (95% CI, 21.0-38.8) the standard therapy group (P < .001). Median duration of remission was 4.6 months in the inotuzumab ozogamicin group, versus 3.1 months in the standard therapy group (hazard ratio, 0.55; 95% CI, 0.31-0.96). In an analysis including all 326 patients, median PFS was significantly longer in the inotuzumab ozogamicin group (5.0 months versus 1.8 months; hazard ratio, 0.45). Median OS was 7.7 months versus 6.7 months (hazard ratio, 0.77; 97.5% CI, 0.58-1.03).

Among those who achieved a complete remission, 78% in the inotuzumab ozogamicin group had results below the threshold for minimal residual disease, in contrast with 28.1% in the standard group (P < .001).

The rate of serious adverse events was similar between the 2 groups (48% for inotuzumab ozogamicin, versus 46% for standard therapy). Febrile neutropenia was the most frequently reported serious adverse event in both the inotuzumab ozogamicin group (12%) and the standard therapy group (18%).

Veno-occlusive liver disease of any grade was more common in the inotuzumab ozogamicin group (15% versus 1%). Dr Kantarjian explained, however, that veno-occlusive liver disease occurred mainly after subsequent allogeneic stem cell transplantation, and can be avoided by not using double alkylator-preparative regimens and through preventive measures.

Dr Kantarjian said that inotuzumab ozogamicin is “extremely promising” as a single agent, but that combination therapies will lead to the most exciting advances for patients: “the real research will be when we start combining this monoclonal antibody with other monoclonal antibodies, or standard chemotherapy, because then we can improve survival significantly in both the salvage and the front-line setting.

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“In the front line setting, we cure only about 40% to 50% of patients. If we add the monoclonal therapies to standard chemotherapy, we may be able to increase the cure rate, shorten duration of chemotherapy, lessen intensity of the chemotherapy, improve compliance, and reduce long-term toxicity. It may be a situation where we will really see a significant increase in the cure rate of adults with ALL, while minimizing chemotherapy-related side effects and improving compliance.”

Hetty E. Carraway, MD, MBA, associate professor of oncology and staff physician in Hematologic Oncology and Blood Disorders at the Taussig Cancer Institute in Cleveland, Ohio, said that there has been a “desperate need” for novel treatments to address patients with relapsed ALL.

“In the setting of a relapsed leukemia in years past, we did not have many options that helped patients get into a second CR,” she said. “This study is highlighting a novel agent, inotuzumab ozogamicin, which is well-tolerated and, in this paper, demonstrates that patients are more likely to achieve a second CR, compared to prior standard chemotherapies that were used. Hopefully, we can figure out a way to capitalize on obtaining this second CR and maintain that remission for durable improvements in overall survival.”


1. Kantarjian HJ, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia N Engl Jour Med. 12 Jun 2016. doi: 10.1056/NEJMoa1509277 [epub published ahead of print]