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Inotuzumab ozogamicin improves outcomes in adult ALL
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Patients with acute lymphoblastic leukemia were more likely to achieve complete remission and disease levels below the threshold for minimal residual disease with inotuzumab ozogamicin than standard therapy, according to the results of a randomized phase 3 study.
Further, results — published in The New England Journal of Medicine and presented at the European Hematology Association Congress — also showed inotuzumab ozogamicin (CMC-544, Pfizer) prolonged PFS and OS, and more patients assigned the therapy were able to undergo stem cell transplantation.
Hagop M. Kantarjian
Adult patients with ALL face a grim prognosis, with frequent relapses and 3-year DFS rates between 30% and 50%.
“Standard chemotherapy regimens result in complete remission in 31% to 41% of patients who relapse earlier, and just 18% to 25% of those who relapse later,” Hagop M. Kantarjian, MD, chair of the department of leukemia at The University of Texas MD Anderson Cancer Center, said in a press release.
Kantarjian and colleagues compared inotuzumab ozogamicin, a humanized anti-CD22 monoclonal antibody conjugated to calicheamicin, with standard intensive chemotherapy in 326 patients with relapsed or refractory ALL.
The efficacy analysis included data from 218 patients (median age, 47 years; range, 18-79) assigned to inotuzumab ozogamicin for up to six cycles or investigator’s choice standard intensive chemotherapy (n = 109 for each).
Complete remission — including complete remission with incomplete hematologic recovery — and OS served as coprimary endpoints.
Eighty-eight patients assigned inotuzumab ozogamicin achieved a complete remission (80.7%; 95% CI, 72.1-88.7), compared with 32 patients (29.4%; 95% CI, 21-38.8) on standard chemotherapy (P < .001).
Significantly more patients in the inotuzumab ozogamicin arm had bone marrow blast results below the threshold (0.01%) for minimal residual disease (78.4% vs. 28.1%; P < .001). Patients assigned inotuzumab ozogamicin also had longer median duration of remission (4.6 months vs. 3.1 months; HR = 0.55; 95% CI, 0.31-0.96).
The survival analysis included data from 326 patients (inotuzumab ozogamicin, n = 164; standard chemotherapy, n = 162).
Patients assigned inotuzumab ozogamicin achieved a median PFS of 5 months, whereas patients assigned standard chemotherapy demonstrated a median PFS of 1.8 months (HR = 0.45; 97.5% CI, 0.34-0.61).
Median OS was also higher among patients in the inotuzumab ozogamicin arm (7.7 months vs. 6.7 months; HR = 0.77; 97.5% CI, 0.58-1.03).
The safety analysis included data from 259 patients (inotuzumab ozogamicin, n = 139; standard therapy, n = 120). Both groups had similar rates of any grade (48% vs. 46%) and grade 3 or worse (46% vs. 43%) adverse events.
Fifteen patients in the inotuzumab ozogamicin group experienced veno-occlusive liver disease, compared with one patient on standard chemotherapy.
The researchers observed 17 grade 5 adverse events in the inotuzumab ozogamicin arm and 11 in the standard chemotherapy arm. Six grade 5 adverse events were fatal (inotuzumab ozogamicin, n = 4; standard chemotherapy, n = 2) and deemed treatment related.
More patients assigned inotuzumab ozogamicin underwent stem cell transplantation after treatment, according to Kantarjian.
“Forty-one percent of patients with ALL in the study were able to proceed to transplant after receiving inotuzumab ozogamicin, compared with the 11% we have seen qualify through standard chemotherapy,” Kantarjian said. “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.” – by Cameron Kelsall
Disclosure: Pfizer provided funding for this study. Kantarjian reports grants from Amgen, Ariad, Bristol-Myers Squibb, Novartis and Pfizer outside of the submitted work. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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