Inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-HCVD) with or without blinatumomab versus standard intensive chemotherapy (HCVAD) as frontline therapy for older patients with Philadelphia chromosome-negative acute lymphoblastic leukemia: A propensity score analysis

Abstract

Background: The outcome of older patients with newly diagnosed, Philadelphia chromosome (Ph)-negative acute lymphoblastic leukemia (ALL) is poor. The combination of targeted therapy with low-intensity chemotherapy is safe and effective. The objective of the current analysis was to compare the outcome of patients who received a combination of inotuzumab ozogamicin plus low-intensity chemotherapy (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone [mini-HCVD]) with or without blinatumomab versus the outcome of those who received the standard, intensive, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (HCVAD) regimen.

Methods: The authors analyzed 135 older patients with newly diagnosed, Ph-negative ALL who were treated prospectively with standard HCVAD (n = 77) or with the combination of inotuzumab ozogamicin plus mini-HCVD with or without blinatumomab (n = 58). A propensity score analysis was conducted using 1:1 matching using the nearest neighbor matching method.

Results: Propensity score matching identified 38 patients in each cohort. The antibody plus low-intensity chemotherapy combination induced higher response rates (98% vs 88%), with lower rates of early death (0% vs 8%) and lower rates of death in complete remission (5% vs 17%). With propensity score matching, the 3-year event-free survival rates for patients who received HCVAD and those who received the combination of inotuzumab ozogamicin plus mini-HCVD with or without blinatumomab were 34% and 64%, respectively (P = .003), and the 3-year overall survival rates were 34% and 63%, respectively (P = .004). By multivariate analysis, age (P = .019; hazard ratio, 1.045) and the combination of inotuzumab plus mini-HCVD with or without blinatumomab (P = .020; hazard ratio, 0.550) were identified as independent prognostic factors for survival.

Conclusions: The combination of inotuzumab ozogamicin plus mini-HCVD with or without blinatumomab is safe and effective in older patients with newly diagnosed, Ph-negative ALL and confers a better outcome compared with standard HCVAD chemotherapy.

Keywords: blinatumomab; inotuzumab; mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone (mini-HCVD); older acute lymphoblastic leukemia (ALL); outcome.