Abstract Topic: 16. Myeloproliferative neoplasms - Clinical
Background: Resistance or intolerance to first-line hydroxyurea (HU) occurs in ~24% of patients (pts) with polycythemia vera (PV); ruxolitinib (RUX) is a recommended second-line treatment (tx).
Aims: This analysis of data from the large, real-world, multicenter, prospective Observational Study of Pts with Polycythemia Vera in US Clinical Practices (REVEAL; NCT02252159) describes the characteristics and clinical outcomes of pts with PV who switched to RUX after HU.
Methods: The analysis included pts (≥18 y) with PV who received HU ≥3 mo prior to study enrollment and did not switch to alternative tx during the observation period (HU cohort; index: study enrollment date) or who switched to RUX after previous HU (HU-RUX cohort; index: RUX initiation date). Descriptive statistics were used for demographics, disease characteristics, and tx patterns collected between 2014 and 2019. Blood counts, MPN-SAF TSS, and spleen length were analyzed at index, 3 and 12 mo post-index for pts in HU-RUX.
Results: Of 2510 pts enrolled in REVEAL, 1053 were analyzed (HU-RUX, n=147; HU, n=906; Table 1). Median age was similar (HU-RUX, 67 y; HU, 70 y); 44.2% and 51.8% were women in HU-RUX and HU, respectively. For HU-RUX vs HU, median (range) time from diagnosis was 6.9 (0.3-36.3) vs 4.8 (0.1-36.5) y. Median (range) duration of tx in HU-RUX and HU was 2.3 (<0.1-18.4) and 2.2 (0.3-36.3) y. Main reasons for HU discontinuation prior to RUX were lack of efficacy (n=53, 36.1%), adverse events (n=47, 32.0%), and disease progression (n=10, 6.8%). For HU-RUX vs HU, mean (SD) MPN-SAF TSS was higher (27.5 [17.7] vs 17.3 [15.1]) and more pts had a palpable spleen (40.8% vs 9.3%). For HU-RUX vs HU at index, more pts had elevated white blood cell (WBC) counts (16.3% vs 6.2%), the mean (SD) number of phlebotomies (PHL) 6 mo pre-index was higher (1.3 [2.3] vs 0.7 [1.45]), and more had a thrombotic event (TE) history pre-index (27.2% vs 19.3%).For HU-RUX, 92 pts (62.6%) received the recommended initial RUX dose (10 mg, BID). The median (range) RUX tx duration was 1.9 (0.3-4.5) y; 89.1% of pts received RUX for ≥6 mo; 38 pts (25.9%) required dose modifications; and 124 pts (84.4%) remained on RUX tx at study end.
For HU-RUX, MPN-SAF TSS, percentage of pts with palpable spleen, and mean spleen length all decreased from index to 3 and 12 mo on RUX tx (Table 1). The number (n/N) of pts with hematocrit (HCT) >0.45 L/L decreased from 49/145 at index to 19/134 and 16/93 at 3 and 12 mo, respectively. The number (n/N) of pts with WBC counts >10×109/L decreased from 87/145 at index to 66/136 and 48/95 at 3 and 12 mo, respectively. Pts with controlled HCT/WBC more likely had no blood count test at follow-up and therefore were not included in the assessment. Mean (SD) number of PHL decreased from 1.3 (2.3) 6 mo pre-index to 0.5 (1.3) 6 mo post-index; 110 pts (74.8%) no longer required PHL 12 mo post-index. For HU-RUX vs HU, the TE rate post-index was numerically lower (2.7% vs 4.2%; median follow-up, 26 and 44 mo).
Summary/Conclusion: This longitudinal analysis of REVEAL demonstrated that HU-RUX had more severe disease burden vs HU. In HU-RUX, RUX tx resulted in significant improvements in PV-related symptoms, spleen size reduction, and sustained blood parameter improvements. This correlated with a reduction of PHL within 6 mo; most pts became PHL-free at 12 mo. The results validate the efficacy of RUX for tx of PV after HU tx in the real-world; monitoring PV pts on HU tx may help identify those likely to benefit from switching to RUX to meet tx goals and become PHL-free.
Keywords: Hydroxyurea, Clinical trial, Ruxolitinib, Polycythemia vera