Efficacy and Safety of CPX-351 Versus 7+3 in a Phase 3 Exploratory Analysis in Patients with High-Risk/Secondary Acute Myeloid Leukemia (AML) with Prior Hypomethylating Agent Exposure Who Achieved Remission

Autor: Donna E. Hogge, Daniel H. Ryan, Jorge E. Cortes, Jonathan E. Kolitz, Robert J. Ryan, Stefan Faderl, Tara L. Lin, Scott R. Solomon, Matthew J. Wieduwilt, Ellen K. Ritchie, Stephen A. Strickland, Gary J. Schiller
Rok vydání: 2019
Předmět:
Zdroj: Blood. 134:1316-1316
ISSN: 1528-0020
0006-4971
0169-6084
Popis: Introduction: Patients (pts) with newly diagnosed, secondary AML (sAML) may have previously received hypomethylating agent (HMA) therapy for an antecedent hematologic malignancy (eg, myelodysplastic syndrome [MDS]). Outcomes for pts with MDS who progress following HMA therapy are typically poor, with remission rates Methods: Pts were randomized 1:1 to receive 1-2 induction cycles with CPX-351 (100 units/m2 [C 100 mg/m2 + D 44 mg/m2] as a 90-minute infusion on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (C 100 mg/m2/day continuously for 7 days [2nd induction: 5 days] + D 60 mg/m2 on Days 1-3 [2nd induction: Days 1-2]). Pts achieving CR+CRi could receive up to 2 consolidation cycles with CPX-351 (65 units/m2 [C 65 mg/m2 + D 29 mg/m2] on Days 1 and 3) or 5+2 (as in 2nd induction). Pts could receive hematopoietic cell transplantation (HCT) at the discretion of the treating physician. This exploratory subgroup analysis included pts with any prior HMA exposure who achieved CR+CRi to study treatment. Results: A total of 309 pts were enrolled in the study, including 133 (43%) pts who had received prior HMA therapy. Among pts with any prior HMA exposure, 23/62 (37%) receiving CPX-351 and 20/71 (28%) receiving 7+3 (odds ratio [OR] = 1.50 [95% CI: 0.73-3.12]) achieved CR+CRi and were included in this analysis. Baseline characteristics for these pts were generally balanced between treatment arms; 9% and 5% of pts in the CPX-351 and 7+3 arms, respectively, were classified as having therapy-related AML, 78% and 90% had antecedent MDS, and 13% and 5% had antecedent chronic myelomonocytic leukemia. In pts with any prior HMA exposure who achieved CR+CRi to CPX-351 or 7+3, median OS was longer with CPX-351 (14.72 vs 10.17 months; HR = 0.55 [95% CI: 0.26-1.15]; Figure 1). More of the pts with prior HMA exposure who achieved CR+CRi and received CPX-351 underwent HCT versus those who received 7+3 (57% vs 35%; relative risk = 1.39 [95% CI: 0.73-2.67]), and OS landmarked from the HCT date was longer with CPX-351 versus 7+3 (not reached vs 14.09 months; HR = 0.43 [95% CI: 0.12-1.51]; Figure 2). In pts without prior HMA exposure, 50/91 (55%) receiving CPX-351 and 32/85 (38%) receiving 7+3 (OR = 2.02 [95% CI: 1.11-3.69]) achieved CR+CRi; among those who achieved CR+CRi to CPX-351 versus 7+3, median OS was also longer with CPX-351 (26.32 vs 10.43 months). The most common treatment-emergent adverse events (TEAEs) in pts with any prior HMA exposure who achieved CR+CRi were febrile neutropenia (CPX-351: 83%; 7+3: 75%), nausea (48%; 55%), fatigue (48%; 45%), diarrhea (43%; 70%), constipation (43%; 50%), peripheral edema (39%; 65%), and dizziness (13%; 50%). The most common grade ≥3 TEAEs were febrile neutropenia (CPX-351: 83%; 7+3: 75%) and fatigue (22%; 0%). The most common serious TEAEs were febrile neutropenia (CPX-351: 13%; 7+3: 10%), ejection fraction decreased (9%; 10%), and subdural hemorrhage (0%; 10%). There was no early mortality by Day 60 in either arm. Conclusions: Pts with prior HMA exposure for an antecedent hematologic malignancy typically have poor outcomes and are a challenging subgroup of AML. Among pts in this study who had any prior HMA exposure and achieved CR+CRi, CPX-351 increased median OS, the rate of HCT, and median OS landmarked from the HCT date versus 7+3. The safety profile for CPX-351 in this subgroup was consistent with the overall study population and the known safety profile of 7+3. Disclosures Lin: Jazz Pharmaceuticals: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees. Ryan:University of Rochester: Patents & Royalties; AbbVie: Equity Ownership. Ritchie:Ariad, Celgene, Incyte, Novartis: Speakers Bureau; AStella, Bristol-Myers Squibb, Novartis, NS Pharma, Pfizer: Research Funding; Celgene, Novartis: Other: travel support; Jazz Pharmaceuticals: Research Funding; Genentech: Other: Advisory board; Tolero: Other: Advisory board; agios: Other: Advisory board; Pfizer: Other: Advisory board, travel support; Celgene: Other: Advisory board; Celgene, Incyte, Novartis, Pfizer: Consultancy. Strickland:Astellas Pharma: Consultancy; Sunesis Pharmaceuticals: Research Funding; AbbVie: Consultancy; Jazz: Consultancy; Kite: Consultancy; Pfizer: Consultancy. Kolitz:Astellas: Research Funding; Boeringer-Ingelheim: Research Funding; Roche: Research Funding. Schiller:Astellas: Research Funding; Amgen: Other, Research Funding; Genzyme: Research Funding; Gilead: Research Funding; Incyte: Research Funding; J&J: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Karyopharm: Research Funding; Novartis: Research Funding; Onconova: Research Funding; Pfizer Pharmaceuticals: Equity Ownership, Research Funding; Sangamo Therapeutics: Research Funding; FujiFilm: Research Funding; Eli Lilly and Company: Research Funding; Daiichi Sankyo: Research Funding; Constellation Pharmaceutical: Research Funding; Celgene: Research Funding, Speakers Bureau; Agios: Research Funding, Speakers Bureau; Biomed Valley Discoveries: Research Funding; Bristol Myer Squibb: Research Funding. Wieduwilt:Celgene: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Reata Pharmaceuticals: Equity Ownership; Amgen, Leadiant, Merck, Servier: Research Funding. Ryan:Jazz Pharmaceuticals: Employment, Equity Ownership. Faderl:Jazz Pharmaceutics: Employment, Equity Ownership. Cortes:Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; BiolineRx: Consultancy; Sun Pharma: Research Funding; Biopath Holdings: Consultancy, Honoraria; Takeda: Consultancy, Research Funding.
Databáze: OpenAIRE
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