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.

• Authors: Elias J Jabbour, Koji Sasaki, Farhad Ravandi, Nicholas J Short, Guillermo Garcia-Manero, Naval Daver, Tapan Kadia, Marina Konopleva, Nitin Jain, Jorge Cortes, Ghayas C Issa, Jovitta Jacob, Monica Kwari, Philip Thompson, Rebecca Garris, Naveen Pemmaraju, Musa Yilmaz, Susan M O'Brien, Hagop M Kantarjian
• Journal: Cancer (Cancer) Vol. 125 Issue 15 Pg. 2579-2586 (08 01 2019) ISSN: 1097-0142 [Electronic] United States
• PMID: 30985931 (Publication Type: Journal Article)
• Copyright: © 2019 American Cancer Society.

Chemical References

• Antibodies, Bispecific
• Antineoplastic Agents, Immunological
• blinatumomab
• Inotuzumab Ozogamicin

Topics

• Aged
• Aged, 80 and over
• Antibodies, Bispecific (pharmacology, therapeutic use)
• Antineoplastic Agents, Immunological (pharmacology, therapeutic use)
• Female
• Humans
• Inotuzumab Ozogamicin (pharmacology, therapeutic use)
• Male
• Middle Aged
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, mortality)
• Propensity Score
• Survival Rate