Abstract
Introduction: A number of treatment (Tx) options are available for ND AML pts including high-intensity (HI) chemotherapy ("7+3" regimen) followed by consolidation chemotherapy or allogeneic hematopoietic cell transplantation, low/intermediate-intensity (LI) therapies (low-dose cytarabine or hypomethylating agents), best supportive care (BSC), or no Tx. While data describing HCRU by AML pts informs health systems, clinicians, and pts of the requirements for managing AML pts, HCRU studies in this population are lacking. An analysis of ND AML pts from the Connect® MDS/AML Disease Registry was conducted to examine HCRU in pts receiving different Tx modalities.
Methods: The Connect MDS/AML Disease Registry (NCT01688011) is an ongoing, prospective observational cohort study of pts in the USA with ND AML (aged ≥ 55) or myelodysplastic syndromes (aged ≥ 18). All interventions are conducted in accordance with physicians' standard of care. Pt demographics, disease characteristics, and Tx information were collected at screening and every 3 months from AML pts enrolled from December 2013 to March 2018. HCRU was assessed in ND AML pts according to Tx groups defined as HI, LI, BSC, or no Tx initiated ≤ 45 days post-diagnosis. Unplanned hospitalizations related to disease or Tx-related complications were assessed in all pts at 3 and 6 months post-enrollment. Response to Tx was analyzed in pts receiving HI and LI therapy only. Number of transfusion episodes (red blood cell or platelet) was calculated over 6 months post-enrollment, and at each month in pts receiving HI or LI therapy; data for partial months were excluded to accurately assess transfusion episodes/month.
Results: A total of 434 AML pts, treated at 20 academic and 85 community/government centers, were included in the analysis. Median age was 70 years (range 55-92), 65% were male, and 83% were white. 95 (21.9%) pts received BSC/no Tx, 153 (35.3%) received LI therapy and 186 (42.9%) received HI therapy. A higher proportion of pts receiving HI therapy had ≥ 1 hospitalization compared with LI and BSC/no Tx groups (59.7% vs 49.0% vs 24.2%; P < 0.05). Mean number of hospitalization days/month in the HI, LI, and BSC/no Tx groups was 6.8 vs 5.7 vs 3.2 days, respectively. During the first 3 months of Tx, pts in the HI group spent a mean of 20.5 days in hospital vs 11.4 days for pts in the LI group, and 9.5 days for pts receiving BSC/no Tx. During the last 3 months of the study period, the number of hospitalization days decreased across all Tx groups to 10.4, 7.0, and 7.7 days, respectively.
There were significant differences in mean monthly transfusion burden over the first 6 months of the study for pts in the HI and LI groups (4.9 vs 2.7 transfusion episodes/month; P < 0.01). During month 1 post-enrollment, the mean number of transfusion episodes in the HI group was 8.3 vs 3.4 in those receiving LI therapy (P < 0.01 after adjusting for insurance status). Over the 6-month study period, the transfusion rate decreased in both groups with a mean decrease of 6.3 and 1.8 transfusion episodes from month 1 to month 6 for HI and LI therapy, respectively (P < 0.01). At month 4, the transfusion rate in pts receiving HI therapy fell below that of the LI group (Figure), coinciding with the end or near completion of consolidation chemotherapy in the HI group. In logistic regression analyses, pts receiving HI therapy were significantly more likely to achieve complete remission (CR) vs pts receiving LI therapy, after adjusting for age, comorbidities, and disease risk (odds ratio = 4.2, 95% confidence interval 1.7-9.1; P < 0.01). Results from a sensitivity analysis, which excluded pts who had received a transplant, were consistent with the main analysis. Mortality rates were not significantly different between LI and HI groups at day 30 and day 60 but were at day 180 (P < 0.01; Table).
Conclusions: These findings from the Connect MDS/AML Disease Registry highlight the level of HCRU in ND AML pts treated with different intensity therapies. While HCRU, as measured by transfusion burden and unplanned hospitalizations, was highest in the HI group, pts in the HI group were significantly more likely to achieve CR, and had lower mortality rates at a 180-day landmark. Higher HCRU rates during early Tx in the HI group are likely a reflection of cytopenia-related complications due to the highly myelosuppressive nature of HI regimens. Therefore higher HCRU during early therapy in the HI group may be offset by improved pt outcomes.
Abedi:BMS: Speakers Bureau; CIRM: Research Funding; Amgen: Research Funding; Celgene: Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau. Erba:Astellas: Research Funding; Janssen: Research Funding; Janssen: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Amgen: Research Funding; Pfizer: Consultancy, Other: grant; Novartis: Consultancy, Speakers Bureau; Amgen: Research Funding; Novartis: Consultancy, Speakers Bureau; Astellas: Research Funding; Celgene: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Astellas: Research Funding; Janssen: Research Funding; Celgene: Consultancy, Speakers Bureau; Incyte: Consultancy, Speakers Bureau; Amgen: Research Funding; Immunogen: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Janssen: Research Funding; Amgen: Research Funding; Jazz: Consultancy, Speakers Bureau; Immunogen: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Astellas: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Pfizer: Consultancy, Other: grant; Daiichi Sankyo: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Novartis: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Pfizer: Consultancy, Other: grant; Takeda/Millenium: Research Funding; MacroGenics: Consultancy; Pfizer: Consultancy, Other: grant; MacroGenics: Consultancy; Juno: Research Funding; Juno: Research Funding; Seattle Genetics: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Research Funding; Incyte: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Incyte: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau; Takeda/Millenium: Research Funding; Immunogen: Consultancy, Research Funding; MacroGenics: Consultancy; Jazz: Consultancy, Speakers Bureau; Celgene: Consultancy, Speakers Bureau; MacroGenics: Consultancy; Immunogen: Consultancy, Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Juno: Research Funding; Celgene: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Juno: Research Funding; Glycomimetics: Consultancy, Other: Chair, Data and Safety Monitoring Committee; Agios: Consultancy, Speakers Bureau; Daiichi Sankyo: Consultancy, Research Funding; Agios: Consultancy, Speakers Bureau. Pollyea:Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Argenx: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celyad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy; Curis: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Roboz:Novartis: Consultancy; Aphivena Therapeutics: Consultancy; Argenx: Consultancy; Celgene Corporation: Consultancy; Roche/Genentech: Consultancy; Eisai: Consultancy; Astex Pharmaceuticals: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Otsuka: Consultancy; Sandoz: Consultancy; Daiichi Sankyo: Consultancy; Janssen Pharmaceuticals: Consultancy; Orsenix: Consultancy; AbbVie: Consultancy; Eisai: Consultancy; Cellectis: Research Funding; Astex Pharmaceuticals: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Roche/Genentech: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Novartis: Consultancy; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy; Celltrion: Consultancy; Aphivena Therapeutics: Consultancy; Celgene Corporation: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy; Jazz Pharmaceuticals: Consultancy; Orsenix: Consultancy; Otsuka: Consultancy; Bayer: Consultancy; Cellectis: Research Funding. Louis:Celgene: Employment; Cellmedica: Patents & Royalties. Flick:Celgene: Employment. Nifenecker:Celgene: Employment. Kiselev:Celgene: Employment, Equity Ownership. Swern:Celgene: Employment, Equity Ownership. Cogle:Celgene: Other: Steering Committee Member of Connect MDS/AML Registry.
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