Safety and Long-Term Survival Results of the Addition of Inotuzumab Ozogamicin to the Conditioning Regimen of Allogeneic Stem Cell Transplantation: A Single-Center Phase 1,2 Trial

Authors

Issa F Khouri
Kamal Alzahrani
Hagop Kantarjian
Denái R Milton
Alison M Gulbis
Koji Sasaki
Nitin Jain
Nicholas J Short
Tapan Kadia
May Daher
Hind Rafei
Jin S Im
David Marin
Amanda L Olson
Uday Popat
Muzaffar Qazilbash
Jeremy Ramdial
Gabriela Rondon
Samer Srour
Partow Kebriaei
Elizabeth Shpall
Richard Champlin
Elias J Jabbour

Publication Date

5-1-2024

Journal

American Journal of Hematology

Abstract

Here we report on the first prospective study evaluating the safety and long-term survival when an escalating dose of inotuzumab ozogamicin (INO) (0.6, 1.2, or 1.8 mg/m2 on day 13) was added to one alkylator-containing conditioning regimen in patients with relapsed CD22 (+) lymphoid malignancies who were candidates for hematopoietic stem cell transplantation (HSCT). Twenty-six patients were enrolled. Six (23%) of these patients entered the phase 1 study: four were treated at an INO dose of 0.6 mg/m2 and two at dose of 1.2 mg/m2. None of these patients experienced dose-limiting toxicities. The remaining 20 (77%) patients entered the phase 2 part of the study at the maximum dose of 1.8 mg/m2. One patient developed VOD; this patient had received nivolumab immediately before HSCT while simultaneously experiencing hyperacute graft-vs-host disease (GVHD). Treatment-related mortality (TRM) at 5 years was 12%. With a median follow-up of 48.7 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 84% and 80%, respectively. Compared with a historical cohort who received same conditioning for HSCT but without INO (n = 56), the INO group showed no significant differences in incidence of liver toxicity, engraftment time, TRM, or risk of acute GVHD. Patients with lymphoma who received INO had a trend for a better 5-year OS (93% versus 68%) and PFS (93% versus 58%) than those in the control group. In conclusion, our results showed that INO is safe with no increased risk of VOD when combined with one alkylator-containing regimen of HSCT.

Keywords

Humans, Inotuzumab Ozogamicin, Prospective Studies, Recurrence, Hematopoietic Stem Cell Transplantation, Graft vs Host Disease, Alkylating Agents, Transplantation Conditioning

DOI

10.1002/ajh.27254

PMID

38400519

PMCID

PMC11001510

PubMedCentral® Posted Date

5-1-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes