Efficacy

mylotarg-ndaa-comb-efficacy

EFS

In adult patients with newly diagnosed AML, the addition of MYLOTARG nearly doubled median event-free survival (EFS) vs chemotherapy alone1
44% significant reduction in the risk of induction failure, relapse, or death with the addition of MYLOTARG vs chemotherapy alone
With the addition of MYLOTARG, the probability of survival with no events occurring was more than double at 2 and 3 years vs chemotherapy alone1,2*
*Number of censored patients: 62 (46%) in the MYLOTARG + chemo arm, 34 (25%) in the chemotherapy arm.
EFS was a clinically meaningful endpoint in the Phase 3, open-label study
  • MYLOTARG is the first drug approved by the FDA based on EFS as a primary endpoint, defined as the time from randomization to induction failure, relapse, or death1
  • EFS is an indirect measure of durable remission3
Exploratory EFS analyses across a range of patients2
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 can be drawn from these data.
If the hazard ratio was <1, EFS was favored in the MYLOTARG arm.
Chemo=daunorubicin and cytarabine; CHV=Centre Hospitalier de Versailles, Le Chesnay, France; CI=confidence interval; ECOG PS=Eastern Cooperative Oncology Group performance status; ELN=European LeukemiaNet; FDA=US Food and Drug Administration; HR=hazard ratio; NCCN=National Comprehensive Cancer Network.
REFERENCES
1. MYLOTARG Prescribing Information. New York, NY: Pfizer Inc.
2. Data on file. Pfizer Inc, New York, NY.
3. Jen EY, Ko CW, Lee JE, et al. FDA approval: gemtuzumab ozogamicin for the treatment of adults with newly diagnosed CD33‑positive acute myeloid leukemia [published online ahead of print February 23, 2018]. Clin Cancer Res. doi:10.1158/1078-0432.CCR-17-3179.

REMISSION/
MRD-NEGATIVITY

MYLOTARG reduced the need for a second induction1
The majority of patients receiving MYLOTARG achieved remission (CR/CRp) in first induction
  • 19 patients (14.1%) receiving MYLOTARG + chemo required a second induction course compared to 34 patients (25%) receiving chemotherapy alone
*CR was defined as absence of blasts in peripheral blood, with no report of extramedullary, molecular, or cytogenetic disease, blasts <5% in the bone marrow with no Auer rods, and complete blood count recoveries (neutrophils >1000/mm3, platelets >100,000/mm3, and transfusion-independent).
CRp was defined as CR with incomplete platelet recovery (<100,000/mm3).
MRD status evaluated in patients with NPM1 mutation2
MRD-negativity 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 can be drawn from these data.
Chemo=daunorubicin + cytarabine; CR=complete remission; CRp=CR with incomplete platelet recovery; ELN=European LeukemiaNet; MRD=minimal residual disease.
MRD-negativity was defined as <0.1% NPM1 mutation in the bone marrow.3
*Following second consolidation.
REFERENCES
1. Data on file. Pfizer Inc, New York, NY.
2. Lambert J, Lambert J, Nibourel O, et al. MRD assessed by WT1 and NPM1 transcript levels identifies distinct outcomes in AML patients and is influenced by gemtuzumab ozogamicin. Oncotarget. 2014;5(15):6280-6288.
3. Schuurhuis GJ, Heuser M, Freeman S, et al. Minimal/measurable residual disease in AML: a consensus document from the European LeukemiaNet MRD Working Party. Blood. 2018;131(12):1275-1291.

RFS

Median RFS among responding patients with MYLOTARG + chemo (n=110) vs chemotherapy alone (n=100)1
Median RFS was 28 months vs 11.4 months, a 47% reduction in the risk of relapse or death among responding patients, with the addition of MYLOTARG
  • In patients who responded, the probability of maintaining remission and being alive at 3 years was 48% with the addition of MYLOTARG vs 20% with chemotherapy alone
RFS was defined as the time from achievement of CR or CRp to the date of relapse or death.
Chemo=daunorubicin + cytarabine; CI=confidence interval; CR=complete remission; CRp=CR with incomplete platelet recovery; NE=not estimable; RFS=relapse-free survival.
REFERENCE
1. Data on file. Pfizer Inc, New York, NY.

OS

Median OS was 27.5 months with MYLOTARG + chemo vs 21.8 months with chemotherapy alone1
  • OS was a secondary endpoint and there was no statistically significant difference between treatment arms in overall survival1,2
    OS was not powered for statistical significance based on the number of events observed
The use of postremission therapies may have confounded the analysis of OS3
  • 30 patients (22.1%) who failed chemotherapy received MYLOTARG as a component of follow-up therapy1
  • OS was not censored for hematopoietic stem cell transplant (HSCT), with more patients receiving follow-up HSCT in the control arm (32 [24%] in the MYLOTARG + chemo arm vs 53 [39%] in the control arm)1
    Median OS among patients not proceeding to HSCT in the MYLOTARG arm vs the control arm was 23.7 months vs 14.9 months
In the Phase 3, open-label study, 32 patients (24%) treated with MYLOTARG went on to transplant1
  • With MYLOTARG, transplant remains a treatment option
Chemo=daunorubicin + cytarabine; CI=confidence interval; OS=overall survival.
REFERENCES
1. Data on file. Pfizer Inc, New York, NY.
2. MYLOTARG Prescribing Information. New York, NY: Pfizer Inc.
3. Jen EY, Ko CW, Lee JE, et al. FDA approval: gemtuzumab ozogamicin for the treatment of adults with newly diagnosed CD33-positive acute myeloid leukemia [published online ahead of print February 23, 2018]. Clin Cancer Res. doi:10.1158/1078-0432.CCR-17-3179.