NEW YORK (Reuters Health) – Over half of patients with refractory and relapsed acute lymphocytic leukemia (ALL) achieve a complete or partial response when treated with the CD22 monoclonal antibody agent, inotuzumab ozogamicin.

This agent and other monoclonal antibodies “potentially offer the first highly active modalities that produce bone marrow CR (complete response) rates equivalent or superior to those observed with intensive chemotherapy but without the notorious toxicities of the latter,” according to a report from The University of Texas M. D. Anderson Cancer Center in Houston.

Writing in the April 30 online issue of Cancer, Dr. Hagop Kantarjian and colleagues note that 90% of lymphocytic leukemic cells express CD22. Inotuzumab ozogamicin is a CD22 monoclonal antibody conjugated with the toxin calicheamicin. It is rapidly internalized by leukemic cells and causes apoptosis.

In the current study, the authors update their experience using inotuzumab ozogamicin to treat 90 patients with refractory-relapsed ALL, 68% of whom were in salvage 2 or beyond. The patients received inotuzumab as a single dose or in smaller multiple doses, every 3 or 4 weeks.

Seventeen patients had a complete response, 27 had a complete response except for recovery of platelet counts, and 8 had a bone marrow response without recovery of platelets or neutrophils, for an overall response rate of 58%, the investigators found.

The multiple-dose schedule was as effective as the single-dose schedule, they report, but less toxic. For example, persistent liver function abnormalities occurred in 2 of 49 single-dose patients, but not in any of the 41 multiple-dose recipients.

However, response durations were relatively short-lived and the median overall survival was 6.2 months, with a 1-year survival rate of 20%. Median survival was longer for patients in salvage 1 (9.2 months) than for patients in salvage 2 (4.3 months) or salvage 3 and later (6.6 months).

Although the survival benefit was “modest,” it nonetheless allowed 36 of the 90 patients (40%) to undergo allogeneic stem cell transplantation (SCT), Dr. Kantarjian and colleagues point out. That compares with a historical rate of only 17% among patients who achieved a complete response with intensive chemotherapy.

“This suggests that, with proper modifications of the preparative regimens and perhaps with combinations of inotuzumab and chemotherapy before SCT, in the future, we may achieve long-term disease-free survival in a substantial proportion of patients using sequential combined modality strategies and allogeneic SCT,” the authors conclude.

SOURCE: Results of inotuzumab ozogamicin, a CD22 monoclonal antibody, in refractory and relapsed acute lymphocytic leukemia
Cancer 2013.