Inotuzumab Moves Forward in Relapsed/Refractory ALL 

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Single-agent inotuzumab ozogamicin achieved an encouraging overall response rate of 57% in the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL) in a phase II trial reported at the 54th Annual Meeting of the American Society of Hematology (ASH). Response was independent of monthly or weekly schedule and correlated with clearance of leukemia cells from the bone marrow.

No difference was observed in response between the weekly and monthly schedule of administration, though the weekly schedule will be preferred going forward in clinical trials because of less toxicity, said lead author Susan M. O’Brien, MD, Ashbel Smith Professor of Medicine, Professor in the Department of Leukemia, Division of Cancer Medicine, at The University of Texas MD Anderson Cancer Center, Houston.

Clear Benefit

“When we compare inotuzumab data with any regimen or investigational agent in our MD Anderson database, no matter which cohort we look at, there is a clear benefit for inotuzumab in relapsed/refractory ALL,” she stated.

Additional studies of inotuzumab include a pivotal trial of the weekly schedule vs the best standard of care in relapsed/refractory ALL, and a study of inotuzumab in combination with low-intensity chemotherapy in elderly patients with ALL.

CD22 B-cell–specific antigen expression is seen in > 90% of patients with ALL, she explained. Inotuzumab is an antibody-antigen complex that binds to CD22 cells, releasing calicheamicin inside the tumor cell. Calicheamicin is a potent cytotoxic agent that binds to DNA, inducing double-stranded DNA breaks leading to apoptosis of the cell.

Study Data

At the ASH meeting, Dr. O’Brien reported results with inotuzumab in patients with refractory or relapsed CD22-positive ALL (N = 89). The first 10 patients were aged 18 or older, and then the trial was opened to children. Two schedules were studied: weekly and monthly, with the same total dose for both schedules. Patients could receive up to eight cycles.

Median age was 39 years, and about 28% were over age 60; 10% had an ECOG performance status of 2 or higher; 11% had prior allogeneic stem cell transplantation; one-third were receiving third-line or higher salvage therapy; and about 25% had high-risk cytogenetics. More than 90% of patients expressed CD22 antigen.

An overall response rate of 57% was similar in the two arms (weekly vs monthly schedule).

The complete remission rate (eradication of all clinical and/or radiologic evidence of disease) was 18% in both arms; CRp rate (complete response except for platelets < 100 × 109/L) was 29% in the monthly arm and 30% in the weekly arm. CRi (complete response without recovery of neutrophils or platelet counts) was 10% in both arms.

Resistance occurred in 39% and 38% of the two arms, respectively, and there were two deaths in each arm in less than 4 weeks. Cytogenetic complete response was seen in 89% and 90% of patients. Overall, 63% and 70%, respectively, were determined to be minimal residual disease–negative.

Median progression-free survival was 4.9 months, with a progression-free survival rate of 21% at 1 year. Duration of complete response was a median of 7 months, and some patients are still responding at 27 months, Dr. O’Brien said. Median overall survival is 5.6 months; 20% are alive at 1 year, with no difference between the treatment arms.

Median overall survival was 8.8 months for those in first salvage, 4.3 months for those in second salvage, and 7.4 months for those in third or more salvage. “We found the best data in first salvage, not surprisingly,” she stated.

Clinical Toxicity

Although infusion reactions and liver function abnormalities were generally grade 1/2 in both arms, they were significantly more frequent in the monthly schedule (where the full dose was given as one large infusion, rather than spaced out over 3 weeks). Thus, the weekly schedule was chosen to move forward into the forthcoming pivotal trial.

The investigators found that older age, at least two salvage regimens, and Philadelphia chromosome–positive status were associated with slightly lower response rates. ■

Disclosure: Dr. O’Brien reported no potential conflicts of interest.


1. O’Brien S, Thomas D, Jorgensen J, et al: Experience with 2 dose schedules of inotuzumab ozogamicin, single-dose, and weekly in refractory-relapsed acute lymphocytic leukemia. 2012 Annual Meeting of ASH. Abstract 671. Presented December 10, 2012.

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