Ruxolitinib In The Treatment Of Polycythemia Vera: An Update On Health-Related Quality Of Life And Patient-Reported Outcomes

Figures & data

Figure 1 PRISMA diagram of clinical trials of ruxolitinib in polycythemia vera.

Table 1 Common Instruments Used In Myeloproliferative Neoplasms For Quantitatively Measuring Symptoms And Quality Of Life

Abbreviated QoL Instrument	Full title	Scoring	Description	References
MPN-SAF	Myeloproliferative Neoplasm Symptoms Assessment Form	14 individual symptoms scores, multiplied by 10 to achieve 0–100 scale.	3 symptom clusters: Mechanisms related to cytokines (TSS-C); Hyperviscosity (TSS-H), and splenomegaly (TSS-S); MPN SAF is validated in PV.	Emanuel et al^Citation28
				Johansson et al^Citation33
				Scherber et al^Citation24
PSIS	Pruritus Symptom Impact Scale	Five point questionnaire.10 point scale; zero equals “no itching/not bothered at all” and 10 equals “bothered as bad as you can imagine/interfered as bad as you can.”	Evaluates severity, interruption of daily life and improvement or worsening of their itching/pruritus since the start of treatment.	Vannucchi et al^Citation4
EORTC-QLQ-C30	European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire-for all cancer patients.	Multi-item scales and single-item measures. Five functional scales, three symptom scales, a global health status/QoL scale, and six single items. All of the scales and single-item measures range in score from 0 to100.	High score represents a high/healthy status/QoL. High score for a symptom represents a high level of symptomatology. Validated for all cancers but does not capture some hematological symptoms.	Aaronson et al^Citation34
EQ-5D-5L	EuroQOL Group non-disease specific QoL instrument	Measures health outcomes for a wide range of health conditions and treatments. Descriptive system and a visual analogue scale (EQ VAS). Five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.	Endpoints are labeled “best imaginable health state” and “worst imaginable health state.” Scores can be summarized into a single index score that provides a simple measure of health for clinical and economic appraisal.	Herdman et al^Citation35
WPAI	Work Productivity and Activity Impariment Questionnaire	Six-item questionnaire that measures self-reported productivity loss during the past seven days	Questions about absence from work, hours spent at work, reduction in productivity at work, and reduction in productivity while performing regular activities.	Relly et al^Citation3^Citation6
PGIC	Patient Global Impression of Change	Scale from 1 to 7 from “very much improved” to “very much worse”	Evaluates all aspects of patients’ health and assesses in there has been an improvement or decline in clinical status	Dorwkin et al^Citation3^Citation7

Table 2 Published Studies Of Ruxolitinib In PV And Quality Of Life And PRO

Topic	Authors	Year	Patient Group	QoL Instruments	No Of Patients	Outcome	Main Symptom Topics	Limitations	Quality Assessment
QoL PRO	Vannucchi et al^Citation4	2015	PV, intolerant/resistant to HA on RUX	MPN-SAF EORTC-QLQ-C30 PSIS PGIC	222 RUX=110 SOC=112	At week 32, 36/74 had 50% reduction of MPN SAF symptom score. Reduction in score by PSIS. EORTC QLQ-C30 scores were higher compared to standard. PGIC comparable to SOC.	Pruritus Tiredness, Night sweats Headaches DizzinessVision problems Muscle aches Abdominal discomfort Early satiety	Open-label, potential treatment bias	**** >20% missing PRO data
QoL PRO	Mesa et al^Citation11	2016	PV, intolerant/resistant to HA on RUX	EORTC-QLQ-C30MPN-SAFPSISPGIC	222 RUX=110 SOC=112	At week 32, 44% on RUX achieved MID (minimally important difference) in GHS/QoL compared to 9% MPN SAF 49% achieved better total symptom score compared to 5% PSIS Improvement in the 5 components of PSIS as early as week 4 PGIC 46% condition improved at week 4 versus 11%	Fatigue Insomnia Pain Dyspnea Appetite loss Diarrhea, Nausea and vomiting Pruritus Role functioning Cognitive functioning Social functioning Physical functioning	Open label Not powered for statistical comparisons	****
QoL PRO	Passamonti et al^Citation3^Citation8	2017	PV without splenomegaly, intolerant/resistant to HA	MPN-SAF EuroQoL-5D-5L PSIS WPAI PGIC	173 RUX=74 BAT=75	Median percentage change from baseline (−45.3%) in RUX vs BAT. At week 28, 29/64 had 50% or greater reduction in MPN-SAF score. EQ-5D-5L no problems in 5 dimensions and improvement in work productivity. Reduction in score by PSIS. Improvements in scores from PGIC and WPAI.	Pruritus Overall QoL, Fatigue Activity impairment	Open-label	*****
QoL PRO	Mesa et al^Citation23	2016	PV on HA ≥ 4 weeks with cytokine symptom cluster (TSS-C)	MPN-SAF PGIC	110 RUX=54 HA=56	At week 16, ≥50% improvement from baseline TSS-C in 43.4% of RUX no statistically significant	Tiredness Muscle aches, Night sweats Itching	Did not anticipate high proportion of patients achieving endpoint on HA arm	*** Drop-out rate >20%

Notes: ****Represents a quality assessment of 80%, and *****Represents a quality assessment of 100%.

Figure 2 Histograms comparing ruxolitinib with standard therapy or hydroxyurea alone in RESPONSE at 32 weeks, RESPONSE at 28 weeks and RELIEF at 16 weeks. Graph 1 depicts proportion of patients who achieved a ≥50% reduction in the MPN-SAF TSS. The RELIEF study only reported the TSS- C (Cytokine symptoms). Graph 2 depicts the proportion of patients who reported “very much” or “much improved” on the PGIC scale.

Abbreviations: TSS, Total Symptom Score; PGIC, Patient Global Impression of Change.

Table 3 Ongoing Clinical Trials In Polycythemia Vera Incorporating PRO In Efficacy Assessment

Title	Clinical Trial Identifier	PRO Instruments	Phase	Recruitment Status
TGR-1202 + Ruxolitinib in Subjects With Myelofibrosis, MDS/MPN, or Polycythemia Vera Resistant to Hydroxyurea	NCT02493530	MPN-SAF TSS	Phase I	Recruiting
Expanded Treatment Protocol (ETP) of Ruxolitinib in Patients With Polycythemia Vera Who Are Hydroxyurea Resistant or Intolerant and for Whom no Treatment Alternatives Are Available.	NCT02292446	MPN-SAF	Phase III	Completed
SAR302503 in Patients With Polycythemia Vera or Essential Thrombocythemia	NCT01420783	MPN-SAF	Phase II	Completed
Low Dose Interferon Alpha Versus Hydroxyurea in Treatment of Chronic Myeloid Neoplasms (DALIAH)	NCT01387763	EORTC QLQ C-30 and MPN-SAF	Phase III	Active, not recruiting
The Benefit/Risk Profile of AOP2014 in Low-risk Patients With PV (Low-PV)	NCT03003325	Functional Assessment of cancer Therapy-Anaemia (FACT-An) and MPN-SAF TSS	Phase II	Recruiting
Idasanutlin Monotherapy in Patients With Hydroxyurea-Resistant/Intolerant Polycythemia Vera	NCT03287245	MPN-SAF TSS EORTC QLQ-C30 PGIC	Phase II	Recruiting
KRT-232 Compared to Ruxolitinib in Patients With Phlebotomy-Dependent Polycythemia Vera	NCT03669965	MPN-SAF TSS EORTC-QLQ-C30	Phase II	Recruiting

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