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, defi ned in the INO-VATE
ALL study as leukemic cells
comprising <1 x 10 -4 of bone
marrow nucleated cells per
fl ow cytometry. 1
The effi cacy 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 fi rst 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 signifi cantly
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 fi rst 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.