In an update from the ongoing phase III INO-VATE trial, treatment with inotuzumab ozogamicin prolonged overall survival (OS) and progression-free survival (PFS) in patients with relapsed/refractory acute lymphocytic leukemia (ALL), compared with standard care. Hagop Kantarjian, MD, from the University of Texas MD Anderson Cancer Center, presented the results at the European Hematology Association’s 21st Congress.
“Standard chemotherapy regimens result in complete remission in 31 to 41 percent of patients who relapse earlier, and just 18 to 25 percent of those who relapse later,” Dr. Kantarjian said during his presentation of the data. Inotuzumab ozogamicin is a humanized antibody targeting CD22, which is expressed in approximately 90 percent of patients with B-cell ALL, and “may represent an important new [treatment] option in relapsed/refractory ALL.”
He presented updated results from 279 relapsed/refractory ALL patients from 18 countries who underwent randomization to one of two treatment arms:
- inotuzumab: starting dose of inotuzumab ozogamicin 1.8 mg/m2 per cycle (0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15 of a 21- to 28-day cycle) for ≤6 cycles
- investigator’s choice of standard care: either fludarabine/cytarabine/granulocyte colony-stimulating factor, cytarabine + mitoxantrone, or high-dose cytarabine
The first 218 patients (109 in each group; median age = 47 years; age range = 18-79 years) were included in the primary intention-to-treat analysis.
Patients were randomized based on the duration of first complete response (CR; ≥12 months vs. <12 months), salvage therapy lines (2 vs. 1), and age (≥55 years vs. <55 years). Primary endpoints were OS and CR or CR with incomplete hematologic recovery (CRi). Patients who achieved CR or CRi were permitted to undergo hematopoietic cell transplantation (HCT) at the investigator’s discretion.
As of the data cut-off date, the median OS was 7.7 months in the inotuzumab arm, compared with 6.7 months in the standard care arm (hazard ratio [HR] = 0.77; 97.5% CI 0.58-1.03; p=0.0203).
However, the authors reported, “a statistically significant improvement in final OS with inotuzumab versus standard care was not met at the pre-specified significance level (0.0104).”
The two-year OS rates were 23 percent (95% CI 16-30) for patients treated with inotuzumab versus 10 percent (95% CI 5-16) for those treated with standard care, but Dr. Kantarjian and authors noted that the OS departed from the proportional hazards assumption.
Patients receiving inotuzumab also had longer median PFS than patients receiving standard care: 5 months (95% CI 3.7-5.6) versus 1.8 months (95% CI 3.7-5.6; HR=0.45; p<0.0001).
Nearly four times as many patients in the inotuzumab group than the standard care group were able to proceed to HCT (41% vs. 11%; p<0.001). “Given that 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,” Dr. Kantarjian said.
The safety population included 259 patients (139 in the inotuzumab-treated group and 120 in the standard-therapy group) who received one or more doses of the study drug; the remaining 20 patients underwent randomization but did not receive treatment by the cut-off date. Serious, any-grade adverse events (AEs) occurred in 67 patients (48%) in the inotuzumab group and 55 (46%) in the standard-therapy group. The most common grade ≥3 AEs in both groups included febrile neutropenia (24% vs. 49%) and thrombocytopenia (37% vs. 59%).
Hepatic AEs were “much more common” with inotuzumab than with standard care, the authors noted. Veno-occlusive liver disease, for example, occurred in 11 percent of inotuzumab-treated patients and one percent of standard care patients.
“Inotuzumab is well tolerated with appropriate prevention measures,” Dr. Kantarjian said. “My hope is that in the future, inotuzumab will be used not as a single agent but in combination with chemotherapy or with other antibodies, and this will improve the outcomes of people with relapsed/refractory ALL and with newly diagnosed ALL significantly compared with what we see today.”
Kantarjian HM, DeAngelo DJ, Advani AS, et al. Overall survival in relapsed/refractory B-cell acute lymphoblastic leukemia patients receiving inotuzumab ozogamicin vs standard care in the phase 3 INO-VATE study. Abstract LB2233. Presented at the EHA 21st Congress, June 12, 2016; Copenhagen, Denmark.