acute lymphoblastic leukemia

Despite the availability of chemotherapeutic agents for the treatment of acute lymphoblastic leukemia, some patients won’t respond to the drugs or experience relapse.  A phase 3 clinical trial examined the safety profile of inotuzumabozogazamin, a novel chemotherapeutic drug which has a potential to be used for relapsed and refractory acute lymphoblastic leukemia.


There are many available treatment options for acute lymphoblastic leukemia. However, despite treatment with chemotherapeutic drugs, some of the patients won’t respond to these agents or experience relapse. Inotuzumabozogamizin is a novel drug which is tested for its potential use in refractory and relapsed acute lymphoblastic leukemia.

In a study published in Lancet Haematology this 2017, a group of researchers led by Hagop M. Kantarjian did a phase 3 clinical trial examining the adverse effects of inotuzumabozogamizin, a novel chemotherapeutic agent, in the treatment of adult patients with relapsed and refractory acute lymphoblastic leukemia. A total of 326 adults who were diagnosed with relapsed or refractory acute lymphoblastic leukemia from August 27, 3012 to March 8, 2016, were included in the study. Participants were randomized to receive either inotuzumabozogazimin (0.8 mg/m2 on the 1st day, 0.5 mg/m2 on the 8th and 15th day of a 21-28 day cycle for ≤6 cycles) or the standard treatment (either high-dose cytarabine, fludarabine + cytarabine + granulocyte colony stimulating factor, or mitoxantrone + cytarabine). Participants were also followed-up after treatment to determine if they underwent subsequent hematopoietic stem cell transplantation (HSCT). The safety profile of the drugs, with focus on treatment-induced hepatotoxicity, was measured. The diagnosis of veno-occlusive disease during study treatment and thereafter (with or without subsequent HSCT) was also observed in this study.

The results show that treatment-induced hepatotoxicity was higher in the group who received inotuzumabozogazimin (51%) compared to those who received standard therapy (34%). The frequency of veno-occlusive disease diagnosed during treatment and thereafter was also higher in the group who received inotuzumabozogamizin. Overall, among patients with relapsed and refractory acute lymphoblastic leukemia, treatment with inotuzumabozogamizin is associated with more hepatotoxicity compared to the standard treatment.

The authors concluded that, although associated with significant risks including severe hepatotoxicity, HSCT is a treatment option that offers the possibility of a cure.  Compared to patients assigned to standard care, significantly more patients in the inotuzumabozogamizin group achieved complete remission, and more than twice as many proceeded to HSCT.  That means that overall, in spite of the risks inotuzumabozogamicin might still afford patients a long-term survival advantage.  Careful monitoring is recommended to minimize the risks.

Written by Karla Sevilla


Kantarjian, H.M., et al. (2017). Hepatic adverse event profile of inotuzumabozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study. Lancet Haematol.

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