Inotuzumab Ozogamicin Receives FDA Approval for Acute Lymphoblastic Leukemia (ALL)

On 17 August 2017, the United States Food and Drug Administration, FDA, approved treatment for adults with relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL), inotuzumab ozogamicin(marketed as Besponsa).

Approval followed an international multicenter open-label trial involving 326 Philadelphia chromosome-negative or positive relapsed/refractory precursor B-cell ALL patients randomized (1:1). Participants needed at least %5 marrow blasts and one or two previous ALL induction treatments. Philadelphia-positive patients needed failure of at least one tyrosine kinase inhibitor and standard chemotherapy.

Patients received inotuzumab ozogamicin or investigator-selected chemotherapy. Among the initial 218 randomized patients, %35.8 on inotuzumab achieved complete remission averaging 8 months; %89.7 of these were minimal residual disease-negative, meaning no detectable cells escaping treatment that could cause recurrence despite absent clinical findings. With chemotherapy, %17.4 achieved complete remission, disappearance of all disease signs, averaging 4.9 months; %31.6 of these were residual-disease-negative.

Common effects in at least %20 included low white cells (neutropenia, leukopenia), low platelets (thrombocytopenia), infection, anemia, weakness, bleeding, fever, nausea, headache, febrile neutropenia, elevated liver tests (ALT, AST, GGT), abdominal pain and increased bilirubin (jaundice). Common effects leading to discontinuation (≥%2) were infection, thrombocytopenia, jaundice, elevated liver tests and bleeding.

The recommended inotuzumab ozogamicin dosefor the first cycle is, on day 1, 0.8 mg/m2; day 8, 0.5 mg/m2; day 15, 0.5 mg/m2, a three-part total of 1.8 mg/m2. Subsequent doses depend on response.