Efficacy

BESPONSA (inotuzumab ozogamicin) induced significantly more CR/CRi* vs SC

CR/CRi was a primary endpoint and was analyzed in the first 218 patients randomized (remission analysis population) per the statistical plan.3

*CR, per Endpoint Adjudication Committee (EAC), was defined as <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, full recovery of peripheral blood counts (platelets ≥100 x 109/L and absolute neutrophil counts [ANC] ≥1 x 109/L), and resolution of any EMD. CRi, per EAC, was defined as <5% blasts in the bone marrow and the absence of peripheral blood leukemic blasts, incomplete recovery of peripheral blood counts (platelets <100 x 109/L and/or ANC <1 x 109/L), and resolution of any EMD.2

1-sided P value using chi-square test.

  • In the remission analysis of 218 randomized patients, 73% (n=64/88) treated with BESPONSA responded in Cycle 1 and 24% (n=21/88) responded in Cycle 2. All responses occurred within 3 cycles2,4

Median DoR was longer with BESPONSA than with SC2

  • Median duration of CR was 8.0 months (n=39; 95% CI, 4.9-10.4) with BESPONSA vs 4.9 months (n=18; 95% CI, 2.9-7.2) with SC
  • 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

DoR, based on a later cutoff date than CR/CRi, was defined for patients who achieved CR/CRi per investigator’s assessment as time since first response of CR/CRi per investigator’s assessment to the date of a progression-free survival (PFS) event or censoring date if no PFS event was documented.

CI=confidence interval; CR=complete remission; CRi=complete remission with incomplete hematologic recovery; DoR=duration of remission; EMD=extramedullary disease; SC=standard chemotherapy.

References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed February 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
  2. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
  3. Kantarjian HM, DeAngelo DJ, Stelljes M, et al. lnotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740-753.
  4. Data on file. Pfizer Inc., New York, NY.

The rate of MRD negativity* was higher for those receiving BESPONSA vs SC2

MRD was a secondary endpoint analyzed among responding patients in the first 218 patients randomized.3

*Patients were considered MRD negative when leukemic cells comprised <1 x 10-4 of bone marrow nucleated cells, as measured by flow cytometry.

  • MRD-negative CR rate was 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 SC2
  • MRD-negative CRi rate was 69.4% (n=34/49; 95% CI, 54.6-81.7) with BESPONSA vs 23.1% (n=3/13; 95% CI, 5.0-53.8) with SC2
  • In the final ITT analysis of 326 patients, 45.7% (n=42/92) of MRD-negative responses with BESPONSA occurred in Cycle 1, 41.3% (n=38/92) in Cycle 2, and 12.0% (n=11/92) in Cycle 33

The analysis of MRD-negativity rate by cycle was not prespecified and is analyzed among responding patients in the full ITT population (N=326).3

CI=confidence interval; CR=complete remission; CRi=complete remission with incomplete hematologic recovery; ITT=intent to treat; MRD=minimal residual disease; SC=standard chemotherapy.

References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed February 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
  2. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
  3. Data on file. Pfizer Inc., New York, NY.

CR/CRi rates were evaluated across a range of patients2,3

These subgroup analyses were exploratory and not powered to detect statistical significance. Small patient numbers and lack of multiplicity adjustments can be a limitation of these analyses. No conclusion about efficacy in subgroups can be drawn from these data.

Exploratory subgroup analyses

CR/CRi and MRD-negative CR/CRi rates in patient subgroups2-4

These subgroup analyses were exploratory and not powered to detect statistical significance. Subgroup data for CR/CRi rates are presented in the full forest plot. Small patient numbers and lack of multiplicity adjustments can be a limitation of these analyses. No conclusion about efficacy by subgroup can be drawn from these data.

Additionally, MRD-negative CR/CRi rates are presented for the selected subgroups below. MRD negativity rates are derived from a central laboratory subgroup analysis in patients achieving a CR/CRi per EAC from the ITT218 population.

  • Patients were stratified at randomization based on duration of first remission (<12 months vs ≥12 months), salvage status (first or second), and patient age at randomization (<55 years or ≥55 years)

First salvage 95% CI for CR/CRi: BESPONSA, 77.9-94.2; SC, 18.8-40.6. Second salvage 95% CI for CR/CRi: BESPONSA, 49.0-81.4; SC, 16.3-48.1.

First remission <12 months 95% CI for CR/CRi: BESPONSA, 66.0-86.5; SC, 14.6-35.5. First remission ≥12 months 95% CI for CR/CRi: BESPONSA, 71.9-95.6; SC, 24.0-56.6.

§<50% BMB 95% CI for CR/CRi: BESPONSA, 69.3-96.2; SC, 23.5-61.1. ≥50% BMB 95% CI for CR/CRi: BESPONSA, 67.0-86.6; SC, 15.3-35.4.

BMB=bone marrow blast; CI=confidence interval; CR=complete remission; CRi=complete remission with incomplete hematology recovery; EAC=Endpoint Adjudication Committee; HSCT=hematopoietic stem cell transplant; ITT=intent to treat; MRD=minimal residual disease; Ph+=Philadelphia chromosome–positive; SC=standard chemotherapy.

References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed February 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
  2. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
  3. Kantarjian HM, DeAngelo DJ, Stelljes M, et al. lnotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med. 2016;375(8):740-753.
  4. Data on file. Pfizer Inc., New York, NY.

In the INO-VATE ALL study, HSCT rates more than doubled with BESPONSA vs SC2,3

*This rate represents the percentage of patients who proceeded directly to HSCT without the use of additional or follow-up induction therapies.

  • The median time from the last dose of BESPONSA (inotuzumab ozogamacin) to HSCT was 4.9 weeks (n=71; range, 1-19 weeks)3

Consider involving the transplant team early in treatment planning, particularly when assessing a patient receiving BESPONSA for HSCT eligibility.

CI=confidence interval; HSCT=hematopoietic stem cell transplant; SC=standard chemotherapy.

References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed February 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
  2. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
  3. Data on file. Pfizer Inc., New York, NY.

BESPONSA demonstrated a median OS of 7.7 months vs 6.2 months with SC and a 25% relative reduction in the risk of death2,3

The analysis of OS did not meet a prespecified boundary for statistical significance of P=0.0104.

*1-sided P value using log-rank test.

Clinical variables predictive of OS in the INO-VATE ALL study4

A multivariate analysis using stepwise Cox regression modeling identified the following clinical variables associated with improved OS for each arm. Only patients with measurements for relevant variables were included. Small patient numbers are a limitation of these analyses.

CI=confidence interval; CR=complete remission; CRi=complete remission with incomplete hematology recovery; HR=hazard ratio; HSCT=hematopoietic stem cell transplant; MRD=minimal residual disease; OS=overall survival; SC=standard chemotherapy.

References
  1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Acute Lymphoblastic Leukemia V.1.2020. © National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed February 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content or its use or application and disclaims any responsibility for its use or application in any way.
  2. BESPONSA Prescribing Information. New York, NY: Pfizer Inc.
  3. Data on file. Pfizer Inc., New York, NY.
  4. 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.