Inotuzumab Ozogamicin: A Review in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukaemia
The intravenous CD22-directed antibody drug conjugate inotuzumab ozogamicin (Besponsa®) is approved in several countries including in the USA, EU and Japan, as monotherapy for the treatment of adults with relapsed/refractory B-cell acute lymphoblastic leukaemia (ALL). In adults with relapsed/refractory B-cell ALL who had received one or two prior treatment regimens, inotuzumab ozogamicin was associated with significantly higher rates of complete remission (including complete remission with incomplete haematological recovery) [CR/CRi] than standard therapy in the pivotal INO-VATE ALL trial. Inotuzumab ozogamicin was associated with significantly longer progression-free survival (PFS), duration of remission and higher haematopoietic stem cell transplantation (HSCT) rates than standard therapy. Although there was no significant between-group difference in overall survival duration as per the study design, the 2-year survival probability in the inotuzumab ozogamicin arm was twice that in the control arm. Inotuzumab ozogamicin had an acceptable tolerability profile. Thus, inotuzumab ozogamicin is an important new treatment option for patients with relapsed/refractory CD22-positive B-cell ALL.
During the peer review process, the manufacturer of inotuzumab ozogamicin was also offered the opportunity to review this article. Changes from comments received were made on the basis of scientific and editorial merit.
Compliance with Ethical Standards
The preparation of this review was not supported by any external funding.
Conflict of Interest
Zaina T. Al-Salama is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.
- 1.National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: acute lymphoblastic leukemia (version 1.2018). 2018. http://www.nccn.org. Accessed 9 Jul 2018.
- 6.European Medicines Agency. Besponsa (inotuzumab ozogamicin): EU summary of product characteristics. 2017. https://www.ema.europa.eu. Accessed 9 Jul 2018.
- 7.US FDA. Besponsa (inotuzumab ozogamicin) for injection, for intravenous use: US prescribing information. 2017. https://www.accessdata.fda.gov. Accessed 9 Jul 2018.
- 9.Pfizer Japan Inc. Besponsa (inotuzumab ozogamicin): Japanese prescribing information. 2018. https://www.pmda.go.jp. Accessed 9 Jul 2018.
- 15.Jani D, Nowak J, Chen Y, et al. Assessment of clinical immunogenicity of inotuzumab ozogamicin in patients with non-Hodgkin lymphoma and acute lymphoblastic leukemia. AAPS Open. 2018; https://doi.org/10.1186/s41120-018-0021-5.
- 16.Garrett M, Ruiz-Garcia A, Parivar K, et al. Characterization of inotuzumab ozogamicin time dependent clearance in relapsed/refractory acute lymphoblastic leukemia patients by nonlinear mixed-effects analysis [abstract no. PI-128]. Clin Pharmacol Ther. 2016;99(Suppl 1):S64–5.Google Scholar
- 17.Advani AS, Jabbour EJ, Stelljes M. Inotuzumab ozogamicin (InO) for relapsed/refractory acute lymphoblastic leukemia (R/R ALL) in the global phase 3 INO-VATE trial: efficacy by MLL status [abstract no. 2557]. Blood. 2017;130(Suppl 1).Google Scholar
- 18.Advani AS, Jabbour EJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard of care for relapsed/refractory acute lymphoblastic leukemia in the phase 3 randomized INO-VATE trial: outcomes by salvage treatment phase [abstract]. Blood. 2016;128(22):5188.Google Scholar
- 19.Jabbour E, Advani A, Stelljes M, et al. Prognostic implications of pretreatment cytogenetics in adults with relapsed/refractory acute lymphoblastic leukemia treated with inotuzumab ozogamicin [abstract no. P519]. Haematologica. 2017;102(Suppl 2):198.Google Scholar
- 20.Kantarjian HM, Stock W, Cassaday RD, et al. Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia in the global phase 3 INO-VATE trial: efficacy and safety by baseline CD22 expression level [abstract no. 1272]. Blood. 2017;130(Suppl 1).Google Scholar
- 21.Su Y, Van Oostrum I, Vandendries E, et al. Hospitalization for patients in the United States (US) and European Union (EU) treated with inotuzumab ozogamicin (InO) vs standard of care (SOC) for relapsed/refractory acute lymphoblastic leukemia (R/R ALL) in a global phase 3 trial [abstract no. e18500]. J Clin Oncol. 2017;35(15 Suppl).Google Scholar
- 22.van Oostrum I, Su Y, Heeg B, et al. Quality-adjusted life years (QALY) for inotuzumab ozogamicin vs standard of care for relapsed/refractory acute lymphoblastic leukemia (R/R ALL) [abstract no. e18506]. J Clin Oncol. 2017;35(15 Suppl).Google Scholar
- 23.Kantarjian HM, DeAngelo DJ, Stelljes M. Inotuzumab ozogamicin (InO) vs standard of care (SC) in patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL): long-term results of the phase 3 INO-VATE study [abstract no. 2574]. Blood. 2017;130(Suppl 1).Google Scholar
- 24.European Medicines Agency. Besponsa (inotuzumab ozogamicin): EU assessment report. 2017. https://www.ema.europa.eu. Accessed 9 Jul 2018.
- 26.Kantarjian HM, DeAngelo DJ, Advani AS, et al. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Lancet Haematol. 2017;4(8):e387–e98.CrossRefPubMedGoogle Scholar
- 28.Cassaday RD, De Angelo DJ, Martinelli G, et al. Extensive safety profile of inotuzumab ozogamicin (Ino) in relapsed/refractory acute lymphoblastic leukemia (ALL) patients enrolled in the phase 3 INO-VATE trial [abstract no. 7029] J Clin Oncol. 2018;36(Suppl).Google Scholar
- 30.National Institute for Health and Care Excellence (NICE). Inotuzumab ozogamicin for treating relapsed or refractory B-cell acute lymphoblastic leukaemia: final appraisal determination. 2017. https://www.nice.org.uk. Accessed 9 Jul 2018.