BESPONSA SC

Median OS in patients treated with BESPONSA was 7.7 months ( 95 % CI , 6.0-9.2 ) vs 6.2 months ( 95 % CI , 4.7-8.3 ) in patients treated with SC ( HR = 0.75 ; P = 0.0105 ). ^‡ The analysis of OS did not meet a prespecified boundary for statistical significance of P = 0.0104 . ^{1 , 2}

The most common ( ≥2 %) serious adverse events were infection , febrile neutropenia , hemorrhage , abdominal pain , pyrexia , VOD , and fatigue ^{1 , 2}

Study design : INO-VATE ALL was a Phase 3 , open-label , randomized ( 1:1 ) study of BESPONSA vs investigator ’ s choice of SC in 326 adult patients with relapsed or refractory B-cell precursor ALL . The primary endpoints of the study were CR / CRi and OS . The secondary endpoints were MRD-negativity , HSCT rate , and DoR . Inference regarding statistical significance of secondary endpoints should not be made . SC included FLAG , HiDAC , or Ara-C + MXN . All patients were required to have ≥5 % bone marrow blasts and to have received 1 or 2 previous induction chemotherapy regimens for ALL . Patients with Ph + B-cell precursor ALL were required to have failed treatment with ≥1 TKI and SC . Single-agent BESPONSA was given by 1-hour IV infusion in 3 fractionated doses at 1.8 mg / m ² each 3- to 4-week cycle , reduced to 3 fractionated doses at 1.5 mg / m ² per cycle after achieving CR / CRi , for up to 6 cycles . For patients proceeding to HSCT , the recommended treatment duration with BESPONSA is 2 cycles . Patients who do not achieve a CR or CRi within 3 cycles should discontinue treatment . ^{1 , 3}

Ara-C + MXN = cytarabine + mitoxantrone ; CI = confidence interval ; CR = complete remission ; CRi = CR with incomplete hematologic recovery ; DoR = duration of remission ; FLAG = fludarabine , Ara-C , and granulocyte colony-stimulating factor ; HiDAC = high-dose cytarabine ; HR = hazard ratio ; HSCT = hematopoietic stem cell transplant ; IV = intravenous ; MRD = minimal residual disease ; OS = overall survival ; Ph += Philadelphia chromosome – positive ; SC = standard chemotherapy ; TKI = tyrosine kinase inhibitor ; VOD = hepatic veno-occlusive disease .

* Response assessments were performed in the first 218 patients randomized . ^† 1-sided P value using chi-square test . ^‡ 1-sided P value using log-rank test .

Infusion-Related Reactions : Infusion-related reactions ( all Grade 2 ) were reported in 4 / 164 patients ( 2 %). Premedicate with a corticosteroid , antipyretic , and antihistamine prior to dosing . Monitor patients closely during and for at least 1 hour after the end of the infusion for the potential onset of infusion-related reactions including symptoms such as fever , chills , rash , or breathing problems . Interrupt the infusion and institute appropriate medical management if an infusion-related reaction occurs . Depending on the severity , consider discontinuation of the infusion or administration of steroids and antihistamines . For severe or life-threatening infusion reactions , permanently discontinue BESPONSA .

QT Interval Prolongation : Increases in QT interval corrected for heart rate using Fridericia ’ s formula of ≥60 msec from baseline were measured in 4 / 162 patients ( 3 %). Administer BESPONSA with caution in patients who have a history of or predisposition to QTc prolongation , who are taking medicinal products that are known to prolong QT interval , and in patients with electrolyte disturbances . Obtain electrocardiograms and electrolytes prior to treatment and after initiation of any drug known to prolong QTc , and periodically monitor as clinically indicated during treatment .

Embryo-Fetal Toxicity : BESPONSA can cause embryo-fetal harm . Apprise pregnant women of the potential risk to the fetus . Advise males and females of reproductive potential to use effective contraception during BESPONSA treatment and for at least 5 and 8 months after the last dose , respectively . Advise women to contact their healthcare provider if they become pregnant or if pregnancy is suspected during treatment with BESPONSA .

Adverse Reactions : The most common ( ≥20 %) adverse reactions observed with BESPONSA were thrombocytopenia , neutropenia , infection , anemia , leukopenia , fatigue , hemorrhage , pyrexia , nausea , headache , febrile neutropenia , transaminases increased , abdominal pain , gamma-glutamyltransferase increased , and hyperbilirubinemia . The most common ( ≥2 %) serious adverse reactions were infection , febrile neutropenia , hemorrhage , abdominal pain , pyrexia , VOD , and fatigue .

Nursing Mothers : Advise women against breastfeeding while receiving BESPONSA and for 2 months after the last dose .

INDICATION

BESPONSA is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia ( ALL ).

Please see brief summary of full Prescribing Information , including BOXED WARNING , on adjacent pages .

References : 1 . BESPONSA Prescribing Information . New York , NY : Pfizer Inc . 2 . Data on file . Pfizer Inc ., New York , NY . 3 . Kantarjian HM , DeAngelo DJ , Stelljes M , et al . Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia . N Engl J Med . 2016 ; 375 ( 8 ): 740-753 .

PP-INO-USA-0351-02 © 2020 Pfizer Inc . All rights reserved . January 2020