Pacritinib May Fill Unmet Symptom Burden Need for Patients With Myelofibrosis With Moderate/Severe Thrombocytopenia

Physical function-related symptoms were prominent in the symptom burden of adult patients with myelofibrosis and moderate or severe thrombocytopenia, according to a retrospective analysis of the phase 3 PERSIST-2 study.

Physical function-related symptoms were prominent in the symptom burden of adult patients with myelofibrosis and moderate or severe thrombocytopenia, according to a retrospective analysis of the phase 3 PERSIST-2 study (NCT02055781) presented at the National Comprehensive Cancer Network (NCCN) 2022 Annual Conference.

“Tiredness and inactivity represent the most prevalent burden for patients with myelofibrosis with moderate to severe thrombocytopenia,” Ruben A. Mesa, MD, the director of The University of Texas Health San Antonio MD Anderson Cancer Center, said.

Data from the analysis showed that tiredness was the most severe symptom in the overall population (N = 259) with a median symptom severity score of 6. Patients with moderate or severe baseline thrombocytopenia were included and stratified by baseline platelet count; 50-100 × 109/L (n = 118) vs less than 50 × 109/L (n = 141).

Patients with severe thrombocytopenia had a higher combined median score of tiredness plus inactivity compared with patients with moderate thrombocytopenia, 12 vs 10, respectively (P = .014).1

Investigators of the PERSIST-2 study (NCT02055781) evaluated the safety and efficacy of the oral JAK2 inhibitor pacritinib (Vonjo) in adult patients with primary or secondary myelofibrosis. To be eligible for the trial, patients needed to have a platelet count of 100 × 109/L or less. Prior treatment with a JAK2 inhibitor was permitted.

The trial randomized a total of 311 patients 1:1:1 to receive pacritinib 400 mg once daily, pacritinib 200 mg twice daily, or best available therapy. The coprimary end points of the trial were spleen volume response of at least a 35% at week 24 and at least a 50% total symptom score (TSS) reduction at week 24.

On February 28, 2022, the FDA granted pacritinib an accelerated approval for the treatment of adults with intermediate or high-risk primary or myelofibrosis with a platelet count below 50 × 109/L. The approval was based on results from PERSIST-2.2

In the analysis presented at the NCCN 2022 Annual Conference, symptom scores were evaluated using TSS 2.0 and were averaged for the week prior to randomization. Symptom prevalence was defined by a symptom score of at least 1 on a scale of 1 to 10.

Patients in the moderate group had a median age of 69 years (range, 64-74) compared with 67 years (range, 62-74) in the severe group. The median platelet count in moderate group was 28 × 109/L (range, 18 × 109/L to 40 × 109/L) vs 70 × 109/L (range, 58 × 109/L to 82 × 109/L) among patients with a higher platelet count. Median hemoglobin was comparable in both arms, 9.2 g /dL (range 8.2 g/dL to 10.6 g/dL) and 9.4 g/dL (range, 8.4 g/dL to 11.0 g/dL) in the lower and higher platelet count arms, respectively. Patients with peripheral blasts of at least 1% were more common in the moderate cohort (48.2%) compared with the severe group (40.7%).

Patients with moderate thrombocytopenia had a mean TSS score of 22 and the average TSS score in this group was 23.7 (range, 4.0-58.4). Similarly, patients with severe thrombocytopenia had a median TSS score of 23 and the average TSS score was 25.7 (range, 3.0-64.3).

Additional results from the analysis showed that inactivity had a symptom severity score of approximately 5.5 and approximately 4.5 among patients in the moderate and severe cohorts, respectively. In terms of spleen-related symptom severity, patients with moderate thrombocytopenia had median symptom severity scores of approximately 5 for early satiety, approximately 3 for abdominal discomfort, and 2.5 for left rib pain. For patients with severe thrombocytopenia, these scores were approximately 5, approximately 4, and approximately 2, respectively.

Patients with moderate disease also had higher median symptom severity scores compared with those with severe disease for the cytokine-related symptoms of night sweats (approximately 3 vs approximately 2.5, respectively) and bone pain (approximately 2 vs approximately 1.5, respectively).

All symptoms examined in the analysis had a prevalence of at least 50% at both platelet levels. Common symptoms in the moderate group included tiredness (approximately 95%), inactivity (approximately 90%), early satiety (approximately 90%), abdominal discomfort (approximately 80%), and night sweats (approximately 70%). Among patients with severe thrombocytopenia common symptoms were made up of tiredness (approximately 95%), inactivity (approximately 85%), early satiety (approximately 85%), abdominal discomfort (approximately 75%), and night sweats (approximately 70%).

“As pivotal phase 2 studies for the JAK1/2 inhibitors ruxolitinib [Jakafi] and fedratinib [Inrebic] excluded patients based on lower platelet counts less than 50,000/µL or 100,000/µL, respectively, an unmet need remains for therapies that can improve symptomatic disease with myelofibrosis and limits [the effect] to their platelet count; pacritinib may fill this role,” Mesa said. “These data are even more relevant in light of the recent approval of pacritinib for patients with a platlet count of less than 50,000/µL.”

Specifically, pacritinib showed a marked spleen volume reduction of at least 35% compared with BAT. Among Investigators individuals with a platelet count of less than 50 × 109/L, those who received pacritinib at the recommended 200-mg twice-daily dose (n = 31), 29.0% (95% CI, 14.2%-48.0%) had a reduction in symptom burden vs 3.1% (95% CI, 0.1%-16.2%) of those who received BAT (n = 32).3

In terms of TSS, 26% of patients who received pacritinib had a reduction of at least 50% using the Modified Myelofibrosis Symptom Assessment Form compared with 9% of those who received BAT.3


  1. Mesa R, Palmer J, Bose P, et al. Symptom burden in patients with myelofibrosis who have moderate or severe thrombocytopenia: a retrospective analysis of patients enrolled in the PERSIST-2 study. J Natl Compr Canc Netw. 2022;20(3.5):CLO22-067. doi:10.6004/jnccn.2021.7287
  2. CTI BioPharma announces FDA accelerated approval of Vonjo (pacritinib) for the treatment of adult patients with myelofibrosis and thrombocytopenia. News release. CTI BioPharma. February 28, 2022. Accessed April 14, 2022.
  3. Vonjo. Prescribing information. CTI BioPharma Corp; 2022. Accessed April 15, 2022.