Efficacy of inotuzumab ozogamicin in patients with Philadelphia chromosome-positive relapsed/refractory acute lymphoblastic leukemia

Cancer. 2021 Mar 15;127(6):905-913. doi: 10.1002/cncr.33321. Epub 2020 Nov 24.


Background: Patients with relapsed/refractory (R/R) Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) have a poor prognosis and limited treatment options.

Methods: The efficacy of inotuzumab ozogamicin (InO), a humanized anti-CD22 monoclonal antibody conjugated to the cytotoxic antibiotic calicheamicin, was evaluated in R/R ALL patients in the phase 1/2 study 1010 (NCT01363297) and open-label, randomized, phase 3 study 1022 (INO-VATE; NCT01564784). This analysis focused specifically on Ph+ R/R ALL patients. In study 1022, Ph+ patients were randomly assigned 1:1 to InO (n = 22) or standard intensive chemotherapy (SC) (n = 27) and 16 Ph+ patients in study 1010 received InO.

Results: In study 1022, rates of complete remission/complete remission with incomplete hematologic recovery (CR/CRi) and minimal residual disease (MRD) negativity (patients achieving CR/CRi) were higher with InO (CR/CRi = 73%; MRD = 81%) versus SC (CR/CRi = 56%; MRD = 33%). The corresponding rates in study 1010 were 56% (CR/CRi) and 100% (MRD). The hematopoietic stem cell transplantation (HSCT) rate in study 1022 was 41% versus 19% for InO versus SC; however, there was no benefit in overall survival (median OS: 8.7 vs 8.4 months; hazard ratio, 1.17 [95% CI, 0.64-2.14]). The probability of being event-free (progression-free survival) at 12 months was greater with InO versus SC (20.1% vs 4.8%).

Conclusion: Given the substantial improvement in responses and rates of HSCT, InO is an important treatment option for patients with R/R Ph+ ALL. Future studies need to consider better characterization of disease characteristics, more sensitive MRD measurements, MRD-directed therapy before HSCT, and potentially combination therapies, including tyrosine kinase inhibitors.

Keywords: Philadelphia chromosome; acute lymphoblastic leukemia; efficacy; hematopoietic stem cell transplantation; inotuzumab ozogamicin.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Inotuzumab Ozogamicin / therapeutic use*
  • Neoplasm, Residual
  • Philadelphia Chromosome
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / mortality
  • Recurrence


  • Inotuzumab Ozogamicin

Associated data

  • ClinicalTrials.gov/NCT01363297
  • ClinicalTrials.gov/NCT01564784

Grant support