BESPONSA ® ( inotuzumab ozogamicin ) is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia ( ALL )
AIM FOR DEEP
REMISSION
Deep remission refers to MRD-negative remission , defined in the INO-VATE ALL study as leukemic cells comprising < 1 x 10 -4 of bone marrow nucleated cells per flow cytometry . 1
The efficacy of BESPONSA was established on the basis of CR ( 35.8 % [ n = 39 / 109 ; 95 % CI , 26.8-45.5 ] with BESPONSA vs 17.4 % [ n = 19 / 109 ; 95 % CI , 10.8-25.9 ] with SC ), the duration of CR ( 8.0 months [ 95 % CI , 4.9-10.4 ] with BESPONSA vs 4.9 months [ 95 % CI , 2.9-7.2 ] with SC ), and the proportion of MRD-negative CR ( 89.7 % [ n = 35 / 39 ; 95 % CI , 75.8-97.1 ] with BESPONSA vs 31.6 % [ n = 6 / 19 ; 95 % CI , 12.6-56.6 ] with SC ) in the first 218 randomized patients . Median duration of CRi was 4.6 months [ n = 45 ; 95 % CI , 3.7-5.7 ] with BESPONSA vs 2.9 months [ n = 14 ; 95 % CI , 0.6-5.7 ] with SC . 1
IMPORTANT SAFETY INFORMATION
WARNING : HEPATOTOXICITY , INCLUDING HEPATIC VENO-OCCLUSIVE DISEASE ( VOD ) ( ALSO KNOWN AS SINUSOIDAL OBSTRUCTION SYNDROME ) and INCREASED RISK OF POST – HEMATOPOIETIC STEM CELL TRANSPLANT ( HSCT ) NON-RELAPSE MORTALITY ( NRM ):
• Hepatotoxicity , including fatal and life-threatening VOD , occurred in patients who received BESPONSA . The risk of VOD was greater in patients who underwent HSCT after BESPONSA treatment . The use of HSCT conditioning regimens containing 2 alkylating agents and last total bilirubin ≥ upper limit of normal ( ULN ) before HSCT were significantly associated with an increased risk of VOD
• Other risk factors for VOD in patients treated with BESPONSA included ongoing or prior liver disease , prior HSCT , increased age , later salvage lines , and a greater number of BESPONSA treatment cycles
• Elevation of liver tests may require dosing interruption , dose reduction , or permanent discontinuation of BESPONSA . Permanently discontinue treatment if VOD occurs . If severe VOD occurs , treat according to standard medical practice
• There was a higher post-HSCT non-relapse mortality rate in patients receiving BESPONSA , resulting in a higher Day 100 post-HSCT mortality rate
Hepatotoxicity , Including Hepatic VOD : Hepatotoxicity , including fatal and life-threatening VOD , occurred in 23 / 164 patients ( 14 %) during or following treatment with BESPONSA or following subsequent HSCT . VOD was reported up to 56 days after the last dose during treatment or follow-up without an intervening HSCT . The median time from HSCT to onset of VOD was 15 days .
Patients with prior VOD or serious ongoing liver disease are at an increased risk of worsening liver disease , including development of VOD , following treatment with BESPONSA . Monitor closely for signs and symptoms of VOD ; these may include elevations in total bilirubin , hepatomegaly ( which may be painful ), rapid weight gain , and ascites . For patients proceeding to HSCT , the recommended duration of treatment with BESPONSA is 2 cycles . A third cycle may be considered for patients who do not achieve a CR or CRi and MRD-negativity after 2 cycles . Monitor liver tests closely during the first month post HSCT , then less frequently thereafter , according to standard medical practice .
Grade 3 / 4 increases in aspartate aminotransferase , alanine aminotransferase , and total bilirubin occurred in 7 / 160 ( 4 %), 7 / 161 ( 4 %), and 8 / 161 ( 5 %) patients , respectively .
Increased Risk of Post-HSCT Non-Relapse Mortality ( NRM ): There was a higher post-HSCT NRM rate in patients receiving BESPONSA , resulting in a higher Day 100 post-HSCT mortality rate . The rate of post-HSCT NRM was 31 / 79 ( 39 %) with BESPONSA and 8 / 35 ( 23 %) with investigator ’ s choice of chemotherapy . In the BESPONSA arm , the most common causes of post-HSCT NRM included VOD and infections . Monitor closely for toxicities post HSCT , including signs and symptoms of infection and VOD .
Myelosuppression : Myelosuppression , and severe , life-threatening , and fatal complications of myelosuppression , including hemorrhagic events and infections , have occurred with BESPONSA . Thrombocytopenia and neutropenia were reported in 83 / 164 patients ( 51 %) and 81 / 164 patients ( 49 %), respectively . Febrile neutropenia was reported in 43 / 164 patients ( 26 %).
Monitor complete blood counts prior to each dose of BESPONSA and monitor for signs and symptoms of infection , bleeding / hemorrhage , or other effects of myelosuppression during treatment and provide appropriate management . As appropriate , administer prophylactic anti-infectives during and after treatment with BESPONSA . Dose interruption , dose reduction , or permanent discontinuation may be required .