Use of Gemtuzumab Ozogamicin for the Treatment of Relapsed or Refractory Acute Myeloid Leukemia (AML) or Acute Promyelocytic Leukemia (APL) in an Expanded Access Setting at Our Cancer Consortium

摘要: INTRODUCTION: Gemtuzumab ozogamicin (GO, MylotargTM) was re-approved by the FDA and has been commercially available since September 2017. Prior to re-approval, adults children with relapsed/refractory AML or APL were treated GO obtained through an expanded access program under institutional IND at our Cancer Consortium: Fred Hutchinson Research Center (FHCRC), University of Washington Medical (UWMC), Seattle Children9s Hospital (SCH), Care Alliance (SCCA). METHODS: Between 2014-2017, we enrolled 44 patients (median age 40); patient characteristics are summarized in Table 1. Twelve SCH 32 SCCA/UWMC. Forty had AML, 3 mixed phenotype acute leukemia 1 APL. Forty-two relapsed disease 2 primary refractory. Median duration CR1 11.2 months (range 0-104). number prior induction attempts 1-8). Eligibility initially required intermediate "good" risk cytogenetics, though subsequently whose blasts CD33 positive included regardless cytogenetics. Additional inclusion criteria ECOG performance status (PS) ≤3, bilirubin ≤2.0 mg/dl, ALT/AST ≤5 fold upper limit normal. RESULTS: Two received single-agent (9mg/m2 day 1), + ATRA Aza, remainder typically 3mg/m2 chemotherapy for a single dose on days 1, 4, 7 (Table 2). Patients median cycles 1-6) (the 6 cycles). Timing around hematopoietic stem cell transplant (HCT) is also noted 2. shows grade 3-4 toxicities occurring within 60 receipt per patients, rather than events. developed sinusoidal obstructive syndrome (SOS) >60 post GO. Both incidences allogeneic (HCT), one 15 HCT other 28 HCT. The first complete resolution SOS remains alive years later, second then died invasive mucormycosis infection setting immunosuppression 37 Six deaths occurred beginning GO: from cardiogenic shock, multiorgan failure aspiration event, pneumonia/sepsis, progression. No attributed Thirteen (29%; 95% CI:18-44%) achieved remission (CR), measurable residual (MRD 7%) 4). MRD detected flow cytometry PCR inversion 16 patient. Sixteen CR incomplete hematologic recovery (CRi) resistant before assessment. Eight remain event free survival (EFS) 31 7-47). Thirty-six have died, 17.2 0.5-9.4). 4 outlines response "more" "less" intense regimens (intensity defined 2) adult vs. pediatric populations. We found higher rates who combined more intensive [78% CR+CRi] less therapy [44% those fewer [100% CR+CRi regimen compared 48% ≥2 regimens]. In addition, responses cytogenetics (11 out 19 total = 58%) unfavorable (3 8 37%), although fraction seen favorable [t(8;21, inv16, t(15;17)] (15 17 88%). CONCLUSION: safe well tolerated. Based salvage regimens, observed 9/28 rate compares expected 7/28 same without (Estey E, Blood [1996/88:756]). combinations reasonable option but might be value only disease. ACKNOWLEDGEMENTS: team wishes acknowledge Pfizer Inc. their commitment supplying drug, Investigational Pharmacy, Institutional Review Board, supporting efforts this making gemtuzumab accessible people refractory AML. Disclosures Walter:Boehringer Ingelheim Pharma GmbH & Co. KG: Consultancy; Genetics, Inc.: Consultancy, Other: Clinical trial support, Funding; Covagen AG: Aptevo Therapeutic: Amphivena Therapeutics: Equity Ownership, Amgen Actinium Pharmaceuticals, Pfizer: Consultancy. Scott:Celgene: Agios: Alexion: Novartis: Funding. Cassaday:Adaptive Biotechnologies: Merck: Amgen: Genetics: Spouse Employment, Jazz Pharmaceuticals: Kite Pharma: Incyte: Becker:GlycoMimetics: