NCCN Guidelines for Acute Myeloid Leukemia V.3.2018 – Follow-up – November 28, 2018

Guideline Page Panel Discussion/References Institution Vote and Request YES NO ABSTAIN ABSENT

AML-12, AML-13, AML-16 Based on a review of the supporting data and FDA label 23 0 0 4 Internal request to review the data and information, the Panel consensus was to add venetoclax in FDA label information for venetoclax in combination with azacitidine or decitabine for the treatment of the combination with azacitidine, decitabine, or following indications: low-dose cytarabine for the treatment of • Candidate for intensive remission induction therapy newly-diagnosed AML in patients who are o Unfavorable cytogenetic/molecular markers/ age 75 or older or who have comorbidities Antecedent hematologic disorder/ that preclude use of intensive induction Therapy-related AML therapy. Based on a review of the supporting data and FDA label information, the Panel consensus was to add venetoclax in External request from AbbVie and combination with azacitidine, decitabine, or low-dose cytarabine Genentech requesting review of the for the treatment of the following indications: updated and published data in patients • Not a candidate for intensive remission induction therapy or with AML and the US Prescribing declines intensive therapy Information for venetoclax. On November • Post-remission therapy for patients treated with lower 21, the FDA expanded the label and intensity therapy approved venetoclax in combination with azacitidine or decitabine or low-dose References cytarabine for the treatment of newly • DiNardo CD, Pratz KW, Letai A, et al. Safety and preliminary diagnosed AML in adults who are age 75 efficacy of venetoclax with decitabine or azacitidine in elderly or older or who have comorbidities that patients with previously untreated acute myeloid leukaemia: a preclude use of intensive induction non-randomised, open-label, phase 1b study. Lancet Oncol chemotherapy. 2018;19:216-228. • Wei A, Strickland SA, Roboz GJ, et al. Phase 1/2 Study of Venetoclax with low-dose Cytarabine in treatment-naive, elderly patients with acute myeloid leukemia unfit for intensive chemotherapy: 1-year outcomes. Blood 2017;130:890-890. • Wei A, Strickland SA, Roboz GJ, et al. Updated safety and efficacy results of phase 1/2 study of venetoclax plus low- dose cytarabine in treatment-naïve acute myeloid leukemia patients aged ≥65 years and unfit for standard induction therapy. Haematologica 2017;Abstract S473. • See FDA Prescribing Information www.fda.gov • See Submission for references.

NCCN Guidelines for Acute Myeloid Leukemia V.3.2018 – Follow-up – November 28, 2018

AML-13 and AML-16 Based on a review of the supporting data and FDA label 23 0 0 4 Internal request to review the data and information, the Panel consensus was to add glasdegib in FDA label information for glasdegib in combination with low-dose cytarabine for the treatment of the combination with low-dose cytarabine for following indications: the treatment of newly diagnosed AML in • Not a candidate for intensive remission induction therapy or patients who are age 75 or older or who declines intensive therapy have other chronic health conditions or • Post-remission therapy for patients treated with lower diseases that may preclude the use of intensity therapy intensive chemotherapy. References • Cortes JE, Heidel FH, Heuser M, et al. A phase 2 randomized study of low dose Ara-C with or without Glasdegib (PF- 04449913) in untreated patients with acute myeloid leukemia or high-risk myelodysplastic syndrome. Blood. 2016;128:99- 99. • See FDA Prescribing Information www.fda.gov AML-F Based on a review of the data and the FDA label information, the 23 0 0 4 Internal request to review the data and Panel consensus was to add gilteritinib for patients with FDA label information for gilteritinib for the relapsed/refractory disease and a FLT3 mutation. treatment of adult patients who have relapsed or refractory AML with a FLT3 References mutation as detected by an FDA-approved • Perl AE, Altman JK, Cortes J, et al. Selective inhibition of test. FLT3 by gilteritinib in relapsed or refractory acute myeloid leukaemia: a multicentre, first-in-human, open-label, phase 1- 2 study. Lancet Oncol 2017;18:1061-1075. • See FDA Prescribing Information www.fda.gov