Effect of Depression on Health Related Quality of Life and Adherence and Its Correlation with Response Rates in Patients of Chronic Myeloid Leukemia on First Line Imatinib and Nilotinib - a Prospective, Institutional Analysis of Real World Data from India
Authors: Bhatia Pratibha , Mirgh Sumeet Prakash , Khushoo Vishvdeep , Naim Faran , Garg Ambar , Ahmed Rayaz , Agrawal Narendra , Bhurani Dinesh 
Published: November 2019

Introduction: Clinical Depression experienced in Chronic Myeloid Leukemia (CML) is common, with a prevalence of 15- 30%. Compliance to TKI therapy in CML is a crucial factor. However, the lifelong duration of treatment impacts overall health related Quality of Life (QoL) in CML. In the absence of TKI resistance and depression, there is a better prognosis of patients conferring a better QoL and response to therapy.
Methods: 98 patients on first line Imatinib (n=81) and Nilotinib (n=17) with a minimum TKI duration of 6 months were prospectively recruited, including their data on baseline Sokal, Eutos and Hasford Scores. Measures of Depression, QoL and Adherence were evaluated using Patient Health Questionnaire 9 item (PHQ-9), Survey Form - Health Related Quality of Life 36 item (SF-36) and Medication Adherence Rating Scale (MARS), respectively. Correlation of Depressive scores with QoL and Adherence were analysed. Similarly, all three variables were studied for their impact on treatment response (assessed by RQ-PCR-BCR ABL).
Results: Frequency of Depression reported in CML patients was no (n=4), minimal (n=22), mild (n=47), moderate (n=19), moderately-severe (n=5), severe depression (n=1). Adherence was found to be 86%. In our study, majority of our Depressive Scores negatively correlated with QoL domains and Adherence using Pearson Correlation co-efficient (p value&lt;0.05).Similarly, severity of depression was found to be significantly associated with QoL domains using one way ANCOVA, where age was adjusted as covariate. Similarly, on evaluating treatment outcomes using SPSSv.23 in 94 patients, it was found that, there was a positive trend of Depression, QoL, and Adherence with response to therapy. Amongst 94 patients who responded to treatment, 8.5% (n=8) patients were found to be in Complete Cytogenetic Response (CCyR), 59.5% (n=56) patients were in Major Molecular Response (MMR), and 31.9% (n=30) patients were in Deep Molecular Response (MR4) with first line TKIs. Most frequent side effects seen with TKIs were hypopigmentation (94.8%;n=93), weight gain (40.8%;n=40), vomiting (17.34%;n=17), QT prolongation (12.24%;n=12), myalgia (5.1%;n=5), facial puffiness (9.47%;n=9), giddiness (7.1;n=7), leg aches (11.22%;n=11) and nausea (9.1%;n=9). Our study limitations were that a minority of patients who discontinued therapy on long term follow-up owing to personal reasons, may report more clinical depression and worsened QoL which could thereby impact response. Additionally, we only assessed impact on response rates with first line TKIs.
Conclusion: Clinical depression exists in CML which negatively impact QoL and compliance. To conclude, lesser depressive state leads to improved QoL and more adherence, which indirectly produces better response rates to TKI therapy. This could pave the way for screening patients on TKIs for early diagnosis of depression, and its impact on QoL before and after intervention with behavioural or pharmacological therapy.

Disclosures
No relevant conflicts of interest to declare.