Characteristics of High-Risk Polycythemia Vera Patients with Suboptimal Response to First-Line Therapy Who Switched to Ruxolitinib Vs Those Who Did Not Switch: Findings from PV-Switch, a Multinational, Retrospective Chart Review Study
Authors: Koschmieder Steffen , Schulte Clemens , von der Heyde Eyck , Busque Lambert , Boyer-Perrard Françoise , Devos Timothy , Passamonti Francesco , Zuurman Mike W. , Paley Carole , Gilotti Geralyn , Cheng Wendy Y. , Gao Chi , Cheng Mu , Wu Melody , Duh Mei Sheng , Harrison Claire N. 
Published: November 2021

Abstract

Introduction:
Cytoreductive therapy such as hydroxyurea and interferon is recommended for high-risk polycythemia vera (PV) patients (pts) and is often used as first-line (1L) therapy. Yet, nearly a quarter of pts discontinue 1L therapy due to resistance or intolerance, requiring second-line (2L) therapy. While ruxolitinib (RUX) is an FDA- and EMA-approved agent for treating resistant or intolerant PV, many pts continue 1L therapy in real-world clinical practice. With a primary objective to assess the event-free survival (EFS) of RUX as 2L therapy in high-risk PV pts ("switchers") relative to pts who stay on 1L therapy ("non-switchers") after suboptimal response, we initiated a multinational, retrospective chart review study with a recruitment target of 350 pts across 25 clinical sites in 9 countries. This study is the first of its kind; the current analysis describes the characteristics of an interim sample of RUX switchers and non-switchers following suboptimal response to 1L therapy.
Methods:
The analysis included an interim sample of eligible pts with data extracted from medical charts from Feb 2020-Jun 2021. Pt eligibility included those ≥18 years old with JAK2 positive PV diagnosed in 2012 or later and a high-risk constellation, suboptimal response to 1L therapy (criteria in Table 1) after ≥12 months of treatment, and ≥6 months of follow-up after suboptimal response except in the event of death. Pts were excluded if they initiated PV treatment other than RUX after suboptimal response. Pts were classified into switchers vs non-switchers based on whether they switched to RUX following first suboptimal response (i.e., index date). Descriptive statistics were used to summarize criteria for suboptimal response, pt characteristics and comorbidities at any time prior to the index date, and PV-related symptoms 12 months prior to the index date (i.e., baseline period). Analyses were conducted separately for switchers and non-switchers.
Results:
In the interim sample of 137 pts, 44 (32.1%) were classified as switchers and 93 (67.9%) as non-switchers. Switchers tended to be younger at PV diagnosis than non-switchers (mean [SD]: 66.5 [12.0] vs 70.2 [8.5] years) and were more likely to be male (52.3% vs 47.3%). Median (interquartile range) time from PV diagnosis to index date was shorter for switchers than non-switchers (13.6 [12.3-22.3] vs 20.6 [14.7-37.0] months). Distribution of suboptimal response criteria differed for the two groups: "persistence of PV-related symptoms or presence of new PV-related symptoms" was the most common criterion for switchers, reported in 47.7% of pts vs 15.1% of non-switchers, while "the need for ≥3 phlebotomies to maintain hematocrit &lt;45% within 1 year" was most common in non-switchers, reported in 45.2% of pts vs 22.7% of switchers (Table 1).
More switchers (54.4%) than non-switchers (31.2%) had a history of thrombosis at time of PV diagnosis. Commonly reported comorbidities included hypertension (43.2% switchers vs 66.7% non-switchers), cardiac conditions (18.2% vs 29.0%), hypercholesterolemia (9.1% vs 25.8%), and diabetes (2.3% vs 16.1%) and tended to be less prevalent in switchers than non-switchers. The most observed PV-related symptoms in the baseline period for both groups were fatigue (18.2% switchers vs 16.1% non-switchers) and pruritus (15.9% vs 14.0%). Fewer switchers (36.4%) than non-switchers (60.2%) received phlebotomies in the baseline period while the mean (SD) number of procedures was similar (3.8 [2.3] vs 3.9 [2.8]). Spleen size assessment by palpation was available in 13 switchers (29.5%) and 38 non-switchers (40.9%) on index date, with switchers tending to have a lower proportion of normal size (18.2% vs 37.6%) and a higher proportion of mild or moderate splenomegaly (11.4% vs 3.3%).
Conclusions:
This analysis shows the trending existence of clinical differences between switchers and non-switchers, with a milder comorbidity profile in switchers. Moreover, while switchers experienced similar PV-related symptoms relative to non-switchers at baseline, switchers were more likely to experience persistence of PV-related symptoms or presence of new symptoms as their suboptimal response type. Taken together, these two factors may have influenced clinicians' decisions to switch to RUX or continue 1L therapy. Upon completion, this novel study will examine the potential impact of switching vs non-switching on EFS in this population.
Figure 1 Figure 1.

Disclosures
Koschmieder: Alexion: Other: Travel support; Geron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support); AOP Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: (e.g. travel support), Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Shire: Honoraria, Other; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; Karthos: Other: Travel support; Abbvie: Other: Travel support; Baxalta: Membership on an entity's Board of Directors or advisory committees, Other; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, Research Funding; CTI: Membership on an entity's Board of Directors or advisory committees, Other; Image Biosciences: Other: Travel support. Schulte: Novartis: Consultancy. von der Heyde: BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ipsen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees. Busque: Novartis: Consultancy. Boyer-Perrard: Novartis: Consultancy. Devos: Alexion, AstraZeneca Rare Disease Inc.: Consultancy; Novartis: Consultancy; AbbVie: Consultancy; Incyte: Consultancy; Bristol Myers Squibb - Celegene: Consultancy. Passamonti: Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zuurman: Novartis: Current Employment. Paley: Novartis: Ended employment in the past 24 months. Gilotti: Novartis: Current Employment. Cheng: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study.. Gao: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study.. Cheng: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study.. Wu: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study. Duh: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study.. Harrison: Incyte Corporation: Speakers Bureau; Geron: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Keros: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Promedior: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Constellation Pharmaceuticals: Research Funding; Sierra Oncology: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Galacteo: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AOP Orphan Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.