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Letters to the Editor
Germany (EQ-5D-3L) (Online Supplementary Table S2).2,11,12 Median treatment durations for HRQoL-evalu- able patients were 12 cycles and 7 cycles in the Oral-AZA and placebo arms, respectively.
As reported previously, there were no clinically mean- ingful differences in observed mean changes from base- line FACIT-Fatigue or EQ-5D-3L HUI scores within treat- ment arms, or between the Oral-AZA and placebo arms, at any postbaseline visit.2 Longitudinal MMRM analyses confirmed the non-inferiority of Oral-AZA effects on fatigue and overall HRQoL relative to placebo, as the lower bounds of the 95% CI for between-group differ- ences in LS mean changes from baseline did not exceed the predefined MID for worsening on any instrument (Table 1).
In subgroup analyses, observed mean HRQoL scores generally remained similar to baseline over time within each arm. Mean changes in FACIT-Fatigue, EQ-5D-3L HUI, and EQ-5D VAS scores were comparable between treatment arms within patient subgroups defined by cytogenetic risk at diagnosis (intermediate/poor), response after induction (CR/CRi), receipt of consolida- tion chemotherapy (yes/no), ECOG PS score (0-1/2-3), age (<65/65-74/≥75 years), and HRQoL domain score (<25th/25th-74th/≥75th percentile). Overall, 45 HRQoL- evaluable patients experienced relapse with 5-15% blasts and received Oral-AZA for 21 days/cycle. Escalated Oral- AZA dosing was not associated with clinically meaning- ful differences in changes from baseline in mean FACIT- Fatigue, EQ-5D-3L HUI, or EQ-5D VAS scores at any visit compared with 14-day Oral-AZA dosing.
eCDF curves detailing individual FACIT-Fatigue changes from baseline in the Oral-AZA and placebo arms at cycles 3, 6, 12, and 24 generally overlapped, with sim- ilar proportions of patients reporting clinically meaning- ful improvement or deterioration at each visit (Figure 1). Proportions of patients with clinically meaningful deteri- oration for each measure were low in both treatment arms, and rates were similar between arms on each instrument at almost all post-baseline visits (Online Supplementary Figure S1); deterioration rates were signifi- cantly higher in the Oral-AZA arm at cycle 19 (EQ-5D VAS) and cycle 29 (FACIT-Fatigue), but these may have occurred by chance as these analyses did not include any adjustments for multiple testing. Times to confirmed deterioration were similar between the Oral-AZA and placebo arms on each instrument (Figure 2). Estimated median times to confirmed deterioration were 41 weeks for Oral-AZA and 44 weeks for placebo on the FACIT- Fatigue (hazard ratio [HR]: 1.06; 95% CI: 0.80-1.40); 200 and 164 weeks, respectively, on the EQ-5D-3L HUI (HR: 0.91; 95% CI: 0.62-1.34); and not reached versus 136 weeks on the EQ-5D VAS (HR: 0.86; 95% CI: 0.61-1.22). Similar findings were observed when censoring patients at the time of death.
While improving survival is the primary goal of AML treatment, systematic evaluation of the impact of treat- ment on HRQoL is essential because prolonged survival may be less meaningful if accompanied by drug-related HRQoL decrements. To our knowledge, QUAZAR AML- 001 is the first placebo-controlled study to prospectively investigate the impact of long-term maintenance therapy on HRQoL for patients with AML in remission post-IC. At study entry, these older patients (median age 68 years2) reported generally favorable levels of fatigue and overall HRQoL that were comparable to levels in general populations.11,12 Mean FACIT-Fatigue and EQ-5D-3L scores during Oral-AZA treatment remained at or above baseline levels at almost all post-baseline assessments,
and longitudinal MMRM analyses confirmed the nonin- feriority of Oral-AZA relative to placebo for preserving HRQoL. These HRQoL data are also consistent with the reported manageable safety profile and acceptable toler- ability of Oral-AZA in QUAZAR AML-001.2
A potential limitation of this study was that HRQoL assessments were conducted on day 1 of each 28-day treatment cycle, allowing for 14 days of recovery after each 14-day dosing period. Additionally, patients in both arms had to undergo routine hospital visits, testing, and marrow collections, which could potentially negatively affect HRQoL outcomes compared with an “observation- only” approach during AML remission.
Oral-AZA administration offers a number of potential benefits, including optimal convenience for patients, no injection-site reactions, fewer clinic visits and lower asso- ciated costs, and treatment flexibility for long-term use. Findings from QUAZAR AML-001 show that Oral-AZA significantly improves OS and RFS without compromis- ing fatigue or overall HRQoL for patients with AML in remission.
Gail J. Roboz,1,2 Hartmut Döhner,3 Christopher Pocock,4 Hervé Dombret,5 Farhad Ravandi,6 Jun Ho Jang,7 Dominik Selleslag,8 Jiří Mayer,9 Uwe M. Martens,10
Jane Liesveld,11 Teresa Bernal,12 Ming Chung Wang,13 Peiwen Yu,14 Ling Shi,14 Shien Guo,14 Ignazia La Torre,15 Barry Skikne,16,17 Qian Dong,16 Julia Braverman,16
Salem Abi Nehme,15 C. L. Beach16 and Andrew H. Wei18
1Weill Cornell Medical College, New York, NY, USA; 2New York Presbyterian Hospital, New York, NY, USA; 3Ulm University Hospital, Ulm, Germany; 4Kent & Canterbury Hospital, Canterbury, UK; 5Hôpital Saint-Louis, Assistance Publique - Hôpitaux de Paris (AP-HP) and Institut de Recherche Saint-Louis, Université de Paris, Paris, France; 6The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 7Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;
8AZ Sint-Jan Brugge-Oostende AV, Bruges, Belgium;
9University Hospital Brno, Brno, Czech Republic; 10SLK-Kliniken GmbH, MOLIT Institute for Personalized Medicine, Heilbronn, Germany; 11Wilmot Cancer Institute, University of Rochester, New York, NY, USA; 12Hospital Universitario Central de Asturias, Oviedo, Spain; 13Chang Gung Medical Foundation, Kaohsiung, Taiwan; 14Evidera, Waltham, MA, USA; 15Celgene, a Bristol-Myers Squibb Company, Boudry, Switzerland; 16Bristol Myers Squibb, Princeton, NJ, USA; 17University of Kansas Medical Center, Kansas City, KS, USA and 18The Alfred Hospital and Monash University, Melbourne, Vicoria, Australia
Correspondence:
GAIL J. ROBOZ - gar2001@med.cornell.edu doi:10.3324/haematol.2021.279174
Received: May 7, 2021.
Accepted: September 15, 2021.
Pre-published: September 23, 2021.
Disclosures: GJR reports consultancy or advisory board or data and safety monitoring committee of AbbVie, Actinium, Agios, Amphivena, Amgen, Argenx, Array Biopharma, Astex, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Celgene, Celltrion, Daiichi Sankyo, Eisai, Epizyme, GlaxoSmithKline, Helsinn, Janssen, Jasper Therapeutics, Jazz, Mesoblast, MEI Pharma (IDMC Chair), Novartis, Orsenix, Otsuka, Pfizer, Roche/Genentech, Sandoz, Takeda (IRC Chair), Trovagene; and research support from Cellectis. HD reports personal fees from Abbvie, Agios, Astellas, Astex Pharmaceuticals, Helsinn, Janssen, Oxford Biomedicals, and Roche; grants and personal fees from Amgen, Celgene, Jazz Pharmaceuticals, and Novartis; and grants from AROG Pharmaceuticals, Bristol Myers
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