Inotuzumab ozogamicin in the management of acute lymphoblastic leukaemia

ABSTRACT

Whilst most adult patients with acute lymphoblastic leukaemia will go into remission with standard induction chemotherapy, many will relapse. Response rates to standard salvage chemotherapy regimens are low and the outlook on relapse is very poor and associated with significant morbidity and mortality hence the need for newer targeted approaches. Inotuzumab ozogamicin (previously known as CMC-544) is an antibody-drug conjugate and consists of a monoclonal anti-CD22 antibody bound to calicheamicin. The target, CD22, is widely expressed on acute lymphoblastic leukaemia cells making it a potential therapeutic target. The calicheamicin is delivered intracellularly and causes leukaemia cell apoptosis. Overall response rates of 57% were observed in a Phase II study and the final results of a Phase III randomised controlled trial comparing this drug to the investigator choice ‘standard of care’ chemotherapy are eagerly awaited. Whilst initial results are promising, there have been concerns regarding liver toxicity and the incidence of veno-occlusive disease of the liver especially in patients who have previously received or go on to allogeneic stem cell transplant.

KEYWORDS:

• Acute lymphoblastic leukaemia
• Inotuzumab Ozogamicin
• CD22
• calicheamicin
• veno-occlusive disease of the liver
• relapse

Financial & competing interests disclosure

NJ Morley has served on the advisory boards for Roche and Amgen. DI Marks has served on the advisory boards and consulted for Pfizer and Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Most adult patients with ALL will go into remission with standard induction chemotherapy but many will relapse.

• Response rates to standard salvage chemotherapy regimens are low, and the outlook in relapse is very poor and associated with significant morbidity and mortality, hence the need for newer targeted approaches.

• Inotuzumab ozogamicin (Previously known as CMC-544) is an antibody drug conjugate and consists of a monoclonal anti-CD22 antibody bound to calicheamicin.

• The target, CD22, is widely expressed on acute lymphoblastic leukemia cells making it a potential therapeutic target.

• Overall response rates of 57% were seen in a Phase II study, and final results of a Phase III randomized controlled trial comparing this drug to investigator choice ‘standard of care’ chemotherapy are awaited.

• Whilst initial results are promising, there have been concerns regarding liver toxicity and the incidence of veno-occlusive disease of the liver especially in patients who have previously received or go on to allogeneic stem cell transplant.

• This drug is likely to become a standard of care treatment for relapsed ALL in adults

• Future studies investigating the role of this drug in the front line setting are needed.