Characteristics and Clinical Outcomes in Patients (Pts) With Polycythemia Vera (PV) Receiving Ruxolitinib (RUX) After Hydroxyurea (HU): A Longitudinal Analysis From REVEAL

Background: Resistance or intolerance to first-line HU occurs in ~24% of pts with PV; RUX is a recommended second-line treatment (tx). In the large, real-world, multicenter, prospective Observational Study of pts with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159), demographics, disease burden, clinical management, and pt-reported outcomes data of pts with PV were collected from 227 community or academic centers between 2014 and 2019. This analysis describes the characteristics and clinical outcomes of pts with PV who switched to RUX after HU tx.

Methods: This analysis included pts (≥18 y) with a clinical diagnosis of PV who were treated with HU at least 3 mo prior to study enrollment and did not switch to an alternative therapy during the observation period (index: study enrollment date) or who switched to RUX after previous HU tx (index: RUX initiation date). Descriptive statistics were used to describe demographics, disease characteristics, and tx patterns. Blood count, Myeloproliferative Neoplasm-Symptom Assessment Form total symptom score (MPN-SAF TSS), and spleen length measurements were analyzed at index and at 3 and 12 mo post index for pts who switched to RUX.

Results:Characteristics of pts who switched to RUX vs who were treated with HU

Out of 2510 pts enrolled in REVEAL,1053 were eligible for this analysis and comprised of 906 pts treated with HU and 147 who switched to RUX (Table 1). Median age for both groups at index was similar (RUX, 67 y; HU, 70 y); 44.2% and 51.8% were women in the RUX and HU groups, respectively. In RUX vs HU, median (range) time to index date from PV diagnosis was 6.9 (0.3-36.3) vs 4.8 (0.1-36.5) y.

The median (range) duration of HU tx prior to index date was 27.6 (0.1-221.0) mo in the RUX and 26.7 (3.0-435.7) mo in the HU group. Main reasons for HU discontinuation prior to RUX tx were lack of efficacy (n=53, 36.1%), adverse events (n=47, 32.0%), and disease progression (n=10, 6.8%). Pts who switched to RUX vs HU had higher mean (SD) MPN-SAF TSS (27.5 [17.7] vs 17.3 [15.1]) and higher percentage of pts (n=40, 27.2% vs n=84, 9.3%) with a palpable spleen. At index, 26 (18.1%) vs 65 (7.8%) pts who switched to RUX vs HU had an elevated white blood cell (WBC) count, with mean (SD) of 16.1 (16.3) vs 9.2 (6.2) ×10⁹/L, respectively. Mean (SD) number of phlebotomies (PHL) 6 mo prior to index date was 1.3 (2.3) in the RUX and 0.7 (1.45) in the HU groups. In RUX vs HU, 27.2% vs 19.3% had a thrombotic event (TE) history prior to index date.

Tx patterns and clinical outcomes in pts who switched to RUX (n=147)

Ninety-two pts (62.6%) received the recommended initial dose of RUX (10 mg BID); additional initial doses were 5 mg BID (n=19), 20 mg BID (n=16), 15 mg BID (n=10), and other (n=10). Seventy-two (49.0%) required a dose modification. The median (range) RUX tx duration was 22.6 (3.0-54.5) mo; most pts (89.1%) received RUX for ≥6 mo. At the end of study, 118 pts (80.3%) were still on RUX.

Compared with index, MPN-SAF TSS, proportion of pts with palpable spleen, and spleen length decreased at 3- and 12-mo follow-up (Table 2). The number of pts with hematocrit >0.45 L/L decreased from 49 at index to 19 and 16 at 3 and 12 mo, respectively (Table 2). The number of pts with WBC counts >10×10⁹/L decreased from 87 at index to 66 and 48 at 3 and 12 mo, respectively (Table 2). Pts with no blood count test at 3- or 12-mo follow-up more likely had controlled hematocrit/WBC at index. Mean (SD) number of PHL decreased from 1.3 (2.3) at index (6 mo prior) to 0.5 (1.3) after 6 mo; 110 pts (74.8%) no longer required PHL 12 mo after index date. The TE rate after index date was numerically lower in RUX vs HU (2.7% vs 4.2%) after a median follow-up of 26 and 44 mo, respectively.

Conclusion: This analysis of REVEAL, the largest real-world cohort of PV pts to date, demonstrated that pts who switched from HU to RUX had more severe disease burden vs those who were treated with HU. RUX tx resulted in significant improvements in PV-related symptoms, correlating with reduction in spleen size and sustained improvement in hematologic parameters. This resulted in a reduction of PHL within 6 mo, with most pts becoming PHL-free at 12 mo. There was also a trend towards lower rates of TEs with RUX. This longitudinal analysis validates the efficacy of RUX for the tx of PV after HU exposure in the real-world and suggests monitoring of PV pts on HU to identify those who are likely to benefit from transition to RUX in order to meet tx goals and become PHL-free.

Gerds:Sierra Oncology: 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; Accurate Pharmaceuticals: Research Funding; Incyte Corporation: Research Funding; Kratos Pharmaceuticals: Research Funding; CTI BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb/Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys/Constellation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees; Imago BioSciences: Research Funding. Grunwald:Genetech/Roche, Incyte Corporation, Janssen: Research Funding; Medtronic: Current equity holder in private company; Daiichi Sankyo, Gamida Cell, Gilead Sciences, Incyte Corporation, Invitae, Karius, Novartis, Ono Pharmaceutical, Pfizer, Pharmacosmos, Premier, Sierra Oncology, Stemline Therapeutics: Consultancy; AbbVie, Agios/Servier, Amgen, Astellas Pharma, Blueprint Medicines, Bristol Myers Squibb, Cardinal Health, CTI BioPharma, Daiichi Sankyo, Gamida Cell, Gilead Sciences, Incyte Corporation, Invitae, Karius, Novartis, Ono Pharmaceuticals, Pfizer, ,: Consultancy. Oh:AbbVie, Blueprint Medicines, Constellation Pharmaceuticals, CTI BioPharma, Disc Medicine, Geron, Incyte Corporation, PharmaEssentia, Sierra Oncology: Consultancy. Braunstein:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Xue:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Bhatt:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Yu:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Mesa:Bristol Myers Squibb: Consultancy; AOP: Consultancy; CTI: Research Funding; Promedior: Research Funding; Blueprint: Consultancy; Samus: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; AbbVie: Research Funding; Constellation Pharmaceuticals, Inc., a MorphoSys Company: Consultancy, Research Funding; LaJolla Pharmaceutical: Consultancy; Gilead: Research Funding; Genotech: Research Funding; Geron: Consultancy; Roche: Consultancy; Celgene: Research Funding; Imago: Research Funding; Novartis: Consultancy; Sierra Oncology: Consultancy, Research Funding.