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HomeAboutDosingEfficacy & SafetyEfficacy & Safety Clinical TrialEfficacySafetySavings & SupportSavings & SupportEventsMaterialsVideosPersonalized patient supportOrdering BESPONSANCCN Guidelines® Recommendations
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Clinical Trial

Study overview

Patient characteristics

Selected patient characteristics

Tab Number 4

Tab Number 5

INO-VATE ALL: a global, randomized, Phase 3 clinical trial1,2

BESPONSA demonstrated efficacy and safety as a single agent vs SC in 326 adult patients with Ph– or Ph+ R/R ALL1-3​

INO-VATE ALL: a global, randomized, Phase 3 clinical trial1,2

1.8 mg/m2 was fractionated as 0.8 mg/m2, 0.5 mg/m2, and 0.5 mg/m2 on Days 1, 8, and 15, respectively. 1.5 mg/m2 was fractionated as 0.5 mg/m2 on Days 1, 8, and 15.
  • The efficacy of BESPONSA was established on the basis of CR, duration of CR, and proportion of MRD-negative CR in the first 218 patients randomized1
Additional inclusion criteria1
  • Patients were required to have ≥5% bone marrow blasts
  • Patients must have received 1 or 2 previous induction chemotherapy regimens for ALL
  • Patients with Ph+ B-cell precursor ALL must have failed treatment with at least 1 TKI and SC
Study populations1,4
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Population-based analysis Patients (n) Description
Remission


 
218


 
Response assessments were performed in the first 218 patients randomized (1:1) per study protocol.
Survival


 
326


 
Survival analyses were completed in the full survival analysis population of 326 patients.
Safety



 
307



 
All randomized patients who received ≥1 dose of study drug, excluding patients who did not initiate therapy (19 patients in the SC arm).
ALL=acute lymphoblastic leukemia; Ara-C + MXN=cytarabine + mitoxantrone; CR=complete remission; CRi=complete remission with incomplete hematologic recovery; DoR=duration of remission; FLAG=fludarabine, cytarabine, and granulocyte colony-stimulating factor; HiDAC=high-dose cytarabine; HSCT=hematopoietic stem cell transplant; MRD=minimal residual disease; OS=overall survival; Ph—=Philadelphia chromosome—negative; Ph+=Philadelphia chromosome—positive; R/R=relapsed or refractory; SC=standard chemotherapy; TKI=tyrosine kinase inhibitor.
References BESPONSA Prescribing Information. New York, NY: Pfizer Inc. 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.  Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019;125(14):2474-2487. Data on file. Pfizer Inc., New York, NY.
Patient characteristics in the INO-VATE ALL trial1-3
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  BESPONSA
(n=164)
SC
(n=162)
Total
(n=326)
Age
Median (range) 46.5 (18-78) 47.5 (18-79) 47.0 (18-79)
<55 years, n (%) 104 (63.4) 103 (63.6) 207 (63.5)
≥55 years, n (%) 60 (36.6) 59 (36.4) 119 (36.5)
ECOG performance status, n (%)
0 62 (37.8) 61 (37.7) 123 (37.7)
1 81 (49.4) 80 (49.4) 161 (49.4)
2 21 (12.8) 20 (12.3) 41 (12.6)
Baseline bone marrow blasts, n (%)
<50% 53 (32.3) 48 (29.6) 101 (31.0)
≥50% 109 (66.5) 113 (69.8) 222 (68.1)
Salvage status, n (%)
First salvage 111 (67.7) 102 (63.0) 213 (65.3)
Second salvage 51 (31.1) 59 (36.4)  110 (33.7)
Prior HSCT, n (%)
Yes 29 (17.7) 32 (19.8) 61 (18.7)
Baseline cytogenetics, n (%)
Normal 46 (28.0) 42 (25.9) 88 (27.0)
Ph+ 22 (13.4) 27 (16.7) 49 (15.0)
t(4;11) 6 (3.7) 8 (4.9) 14 (4.3)
Complex 28 (17.1) 22 (13.6) 50 (15.3)
Other 29 (17.7) 29 (17.9) 58 (17.8)
Duration of first remission, n (%)
<12 months 96 (58.5) 106 (65.4) 202 (62.0)
≥12 months 68 (41.5) 56 (34.6) 124 (38.0)
ECOG=Eastern Cooperative Oncology Group; HSCT=hematopoietic stem cell transplant; Ph=Philadelphia chromosome; SC=standard chemotherapy.
References BESPONSA Prescribing Information. New York, NY: Pfizer Inc.  Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019;125(14):2474-2487. Data on file. Pfizer Inc., New York, NY.
The majority of patients were in first salvage, had no prior HSCT, had high tumor burden (baseline BMBs), and had a short duration of first remission1The INO-VATE ALL study also included patients with Ph+ disease and extramedullary disease (EMD)* or lymphoblastic lymphoma (LBL)1-3

Patients with Ph+ disease were required to have failed treatment with at least 1 TKI and SC.4

Patients with LBL were allowed in the study, provided bone marrow involvement was ≥5%.2

Included lesions that could be accurately measured in 2 dimensions with a greatest transverse diameter of ≥1 cm, palpable lesions with both diameters ≥2 cm, or all other lesions documented by indirect evidence only (eg, lab values).2BMB=bone marrow blast; HSCT=hematopoietic stem cell transplant; Ph–=Philadelphia chromosome–negative; Ph+=Philadelphia chromosome–positive; SC=standard chemotherapy. 
References Kantarjian HM, DeAngelo DJ, Stelljes M, et al. Inotuzumab ozogamicin versus standard of care in relapsed or refractory acute lymphoblastic leukemia: final report and long-term survival follow-up from the randomized, phase 3 INO-VATE study. Cancer. 2019;125(14):2474-2487.  Data on file. Pfizer Inc., New York, NY.  DeAngelo DJ, Advani AS, Marks DI, et al. Inotuzumab ozogamicin for relapsed/refractory acute lymphoblastic leukemia: outcomes by disease burden. Blood Cancer J. 2020;10(8):81. BESPONSA Prescribing Information. New York, NY: Pfizer Inc. 
Efficacy & Safety

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PP-MCL-USA-0367
INDICATIONBESPONSA® (inotuzumab ozogamicin) is indicated for the treatment of adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
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.

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

Please see full Prescribing Information, including BOXED WARNING.