Ruxolitinib Shows Benefit for Certain Patients with Polycythemia Vera


Results from the phase 2 MAJIC-PV study showed that patients with polycythemia vera who are intolerant to hydroxycarbamide chemotherapy had superior efficacy results on ruxolitinib.

Patients with polycythemia vera (PV) that are intolerant or resistant to hydroxycarbamide chemotherapy had superior responses with ruxolitinib compared to patients on the best available therapy (BAT), according to results from the MAJIC-PV (ISRCTN61925716) study.1

Results from the phase 2 open-label, randomized controlled trial of ruxolitinib in these patients who were resistant or intolerant of hydroxycarbamide reached their primary end point of a complete response to treatment within 12 months. CR was defined as hematocrit levels less than 45% without venesection for 3 months; platelets equal to or less than 400 × 109/L; a white blood cell (WBC) count of less than or equal to 10 × 109/L, and normal spleen size. Of the 180 patients eligible for the analysis, 93 patients were randomized to the ruxolitinib arm and 87 were given BAT, of those 93 patients in the ruxolitinib arm 43% (n = 40) had a CR vs 26% (n = 23) in the BAT arm (OR, 2.12; 90% CI, 1.25-3.60, P = .02).

A best response of partial response (PR) was seen in 50 patients (54%) of the patients on ruxolitinib compared with 58 (67%) of patients in the BAT arm during the first year. Between these 2 groups 45 patients in the ruxolitinib arm had a hematocrit level less than 0.45 and were venesection-free for 3 months during their first PR, in comparison, this was seen in 50 patients in the BAT arm. The overall response rate (ORR) was similar between the ruxolitinib and BAT arms, at 97% vs 93%, respectively, but the duration of CR in patients on the JAK2 inhibitor was more durable (HR, 0.38; 95% CI, 0.24-0.61, P < .001).

In the BAT-treatment arm, 52% of patients had at least 1 venesection compared with 29% in the ruxolitinib arm, but hemoglobin and hematocrit levels were lower in the ruxolitinib arm and thromboembolic event-free, but not hemorrhage-free, survival (EFS) was significantly improved with ruxolitinib (HR, 0.56; 95% CI, 0.32-1.00; P = .05). EFS overall was better with ruxolitinib than BAT (HR, 0.58; 95% CI, 0.35-0.94, P = .03) and was associated with a better outcome for patients that had a CR at 12 months (HR, 0.41; 95% CI, 0.21-0.78, P = .01). The 3-year progression-free survival (PFS) continued to demonstrate the effectiveness of ruxolitinib with a PFS of 75% (95% CI, 63%-83%) for BAT and 84% (95% CI, 74%-90%) for ruxolitinib and overall survival showing similar results.

“The MAJIC-PV study delivers several important insights into management of PV patients who are resistant or intolerant to hydroxycarbamide. Novel findings included that ruxolitinib prolonged thrombosis free survival, and event free survival, and that controlling blood count and spleen size was also associated with better EFS,” Claire Harrison, MD, FRCP, consultant hematologist and deputy director, and professor at Guy's and St. Thomas' Hospital, NHS Foundation Trust, told Targeted Oncology™.

What they observed in the study was that ruxolitinib was associated with patients who had a 50% reduction in their VAF (P < .001) and that those who responded to the JAK2V617F molecular inhibitor at a year were also more likely to have a CR (P = .09). This association was also seen for an improved PFS (P =.001), EFS (P = .006), and OS (P = .04) for those patients on ruxolitinib. Moreover, early JAK2V617F molecular responders had an event occur in 24% of responders compared with 43% of non-responders (P = .005).

At a median age of 66 years old with a median follow up of 4.8 years at the time of data cut off, 54 patients were resistant to hydroxycarbamide chemotherapy, 80 patients were intolerant, and 46 were both resistant and intolerant to hydroxycarbamide chemotherapy. Patients with diabetes and hypertension were more prevalent in the ruxolitinib arm, but adverse events (AEs) on this study were consistent with AEs observed on ruxolitinib before.

The most common grade 3 blood related AEs for patients on ruxolitinib included 12 patients with anemia and 20 patients overall with any grade blood related AEs. Thirty-three patients between both arms had any grade infections and infestations with 55 patients on ruxolitinib having any grade respiratory infections and 31 with cutaneous infections. Moreover, the most common any grade malignant neoplasms were a squamous cell carcinoma transformation in 11 patients.

“The MAJIC PV study is the first study ever to show that reduction of the JAK2 V617F variant allele frequency by 50%, which was more frequent with ruxolitinib, was linked to prolonged overall and progression-free survival as well as event free survival. In ruxolitinib molecular responders single cell studies demonstrated that treatment resulted in clearance of diseased stem cells,” said Harrison

Harrison CN, Nangalia J, Boucher R, et al. Ruxolitinib Versus Best Available Therapy for Polycythemia Vera Intolerant or Resistant to Hydroxycarbamide in a Randomized Trial. J Clin Oncol. 2023 May 1:JCO2201935. doi: 10.1200/JCO.22.01935
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