Evaluation of the Impact of Myelosuppression on Treatment Response and Health-Related Quality of Life (HRQoL) in Patients with Chronic Myeloid Leukemia (CML).
Authors: Rosa K. , Crawford B. , Syat B. , Feng W. , Woodman Richard C. 
Published: October 2019

Abstract
Intro: Toxicity profiles (eg, myelosuppression, fluid retention) of 2nd generation tyrosine kinase inhibitors (TKIs) for imatinib resistant/intolerant CML appear to be different (1,2). Myelosuppression (neutropenia, thrombocytopenia, anemia) is commonly experienced by cancer patients (pts) receiving treatment. These cytopenias are associated with increased morbidity and mortality, high healthcare costs, and diminished HRQoL.
Objective: Examine relationship of myelosuppression with treatment response and HRQoL in CML pts.
Methods: Blinded data from the International Randomized IFN versus STI571 (IRIS) study, a multi-center, double-blind randomized controlled trial of newly-diagnosed CML pts (n=1,032), was analyzed to derive relationships of myelosuppression and response as well as between myelosuppression and HRQoL. Response to treatment was assessed by a major cytogenetic response (MCyR) and a complete cytogenetic response (CCyR) at the 3-mo visit. The Functional Assessment of Cancer Therapy-Biologic Response Modifier (FACT-BRM) questionnaire was used to assess HRQoL. As prior research has shown that pts experience most adverse events during the first few months of treatment, 2 groups were compared based on presence or absence of new or worsening Gr 3 or 4 myelosuppression at any time during the first 3 mos. HRQoL was measured at baseline and month 3. MCyR was achieved by ∼28% of pts with no myelosuppression versus 11% of pts with myelosuppression (p<0.0001) (Table 1). CCyR was achieved by significantly more pts with no myelosuppression than those with myelosuppression (12% vs 2%, respectively, p<0.0001). For a majority of the FACT domains, the decline in HRQoL from baseline to 3 mos was significantly greater for pts with vs without myelosuppression (Table 2).
Results: Myelosuppression was related to a negative impact on HRQoL and decreased response rates. Therefore, 2nd generation TKIs may impact HRQoL differently from one another, as the incidence of Gr 3/4 myelosuppression differs among certain TKIs. (1;2) This will be studied further in imatinib resistant or intolerant CML pts.
Table 1. Impact of Myelosuppression on Achieving MCyR and CCyR No Myelosuppression Myelosuppression p-value[1] [1]From Chi-square test of proportions. Proportion Achieving MCyR 28.03 11.06 <0.0001 Proportion Achieving CCyR 12.37 1.92 <0.0001 Table 2. Impact of Myelosuppression on Change in FACT Domains* No Myelosuppression Myelosuppression *Myelosuppression of Gr 3/4 in first 3 mos of study; FACT assessed at 3-mo visit. [1] p-value from Student’s t-test comparing group means. Note: Higher scores represent superior change from baseline scores. FACT Domain N Mean(SD) N Mean(SD) p-value[1] Emotional Well-Being 691 1.190(4.095) 184 0.880(3.838) 0.3560 Physical Well-Being 693 −2.249(6.252) 183 −3.453(5.849) 0.0192 Functional Well-Being 691 −0.972(5.947) 185 −2.419(5.646) 0.0030 Social/Family Well-Being 693 −0.781(4.352) 183 −1.265(4.869) 0.1925 Global Score 669 −2.732(15.301) 182 −6.273(15.150) 0.0057 Trial Outcome Index 670 −4.679(18.075) 181 −9.269(17.866) 0.0025 BRM Cognitive/Emotional 685 −0.0643(4.463) 183 −1.366(4.629) 0.0537 BRM Physical 687 −0.774(4.889) 183 −2.171(5.126) 0.0007