Spleen Volume Reduction Associated With Overall Survival Benefit in Patients With Myelofibrosis Receiving Pacritinib


For patients with myelofibrosis receiving pacritinib, spleen volume reduction was associated with improved overall survival.

Naveen Pemmaraju, MD

Naveen Pemmaraju, MD

Regardless of baseline platelet counts and hemoglobin levels, patients with myelofibrosis achieved improvements in spleen and symptom response with pacritinib (Vojno) comparable with other JAK inhibitors, according to findings from the pivotal phase 3 PERSIST-1 (NCT01773187) and PERSIST-2 (NCT02055781) trials that were presented at the 2023 ASCO Annual Meeting.1,2 Moreover, patients who achieved spleen volume reduction (SVR) also achieved improvements in overall survival (OS).

Symptoms of myelofibrosis include marrow fibrosis, splenomegaly, and progressive cytopenia and prior approved agents include ruxolitinib (Jakafi) and fedratinib (Inrebic).

“The previous 2 JAK inhibitors ruxolitinib and fedratinib were for patients at a certain platelet cutoff, so that’s 50 [x 109/L] and above, and pacritinib ended up becoming approved for patients with myelofibrosis with platelets less than 50 [x 109/L], filling that urgent unmet medical need,” Naveen Pemmaraju, MD, associate professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, said in an interview with Oncology Nursing News®.

Pacritinib is a JAK1-sparing inhibitor of JAK2/IRAK1/ACVR1 associated with improved SVR vs best available therapy (BAT), including ruxolitinib, in patients with myelofibrosis with platelets below 100 x 109/L in the PERSIST-2 trial. However, the relationship between SVR and OS in patients with thrombocytopenia is not well known. As such, investigators evaluated whether SVR with pacritinib or BAT is associated with improved survival in those with thrombocytopenia.

The analysis included patients from PERSIST-2 who were alive and on study who had received 200 mg of pacritinib twice daily or BAT at week 10 (week-12 SVR window).

In the pivotal PERSIST-2 trial, baseline characteristics in the pacritinib arm for responders (n = 65) and nonresponders (n = 24), respectively, were presented for age (median in years: 66 vs 67), Dynamic International Prognostic Scoring System (DIPSS) high risk (18.5% vs 46%), platelet count (median, 58 x 109/L vs 67 x 109/L), hemoglobin (median, 9.7 g/dL vs 9.3 g/dL), red blood cell transfusion requirement (38% vs 58%), prior JAK2 exposure (45% vs 50%), spleen volume (median, 2573 cm3 vs 2094.5 cm3), and palpable spleen length (median, 15.00 cm vs 12.75 cm).

Responders (n = 28) and nonresponders (n = 56) in the BAT arm had median ages of 66 years and 69 years, respectively. Moreover, 21% and 25% of patients, respectively, had DIPSS high-risk disease, median platelet counts of 68 x 109/L and 47 x 109/L, median hemoglobin of 10.0 g/dL and 9.6 g/dL, red blood cell transfusion requirement in 32% and 54%, prior JAK2 exposure in 64% and 45%, median spleen volume of 2907 cm3 and 2393 cm3, and median palpable spleen length of 12.00 cm and 14.50 cm.

Results showed that at least 10% SVR with pacritinib was prognostic for survival between responders and nonresponders (P <.0001). At least 20% and 35% or more SVRs were also prognostic for survival but to a lesser extent, with values of .0199 and .3516, respectively. Authors also noted that any degree of SVR was associated with improved survival with pacritinib (HR, 0.08; 95% CI, 0.01-0.51; P = .0007).

Adjusting for baseline spleen volume and red blood cell transfusion requirement in univariate analysis did not affect the survival benefit with pacritinib at the 10% or greater SVR threshold.

Notably, SVR was not associated with survival with BAT at any threshold (SVR ≥10%, P = .4888; SVR ≥20%, P = .9821; SVR ≥35%, P = .8881).

“What is very encouraging is that we’re starting to see disease modification with these JAK inhibitors, not only showing spleen and symptom improvement, but also trying to show OS improvement and that the two can correlate,” Pemmaraju said. “Once we start to see spleen symptom improvement, as well as OS improvement, we can start to try to aim for and achieve disease modification, [which is] what matters to the patient. We’re starting to see that now, as we did with ruxolitinib and perhaps now with the newer JAK inhibitors.”

Additional findings from the analysis indicated that median dose intensity through week 12 was maintained with pacritinib at 200 mg twice daily in all patients who achieved SVR of at least 10%. Of the 28 patients who achieved SVR of at least 10% on BAT, the majority (n = 23) received ruxolitinib prior to the week-12 SVR evaluation. Of these patients, 78% were receiving no more than 10 mg of ruxolitinib twice daily and 43% were receiving no more than 5 mg of ruxolitinib twice daily. Other BATs included hydroxyurea (Hydrea) and prednisone.

Additionally, OS was associated with achieving at least 20% reduction in spleen length with pacritinib (HR, 0.14; 95% CI, 0.02-1.26; P =.0406; OS by spleen length reduction ≥35% and ≥50%, P =.0990 and P =.3008). However, separation of the curves was not as great for prognostication as SVR among responders and nonresponders.

“As pacritinib can be given at full dose regardless of platelet count, it is possible that pacritinib may offer a unique survival advantage for patients with myelofibrosis with moderate or severe thrombocytopenia who achieve ≥10% spleen reduction,” the authors wrote in the poster.

Although pacritinib is approved for use in patients with low platelet counts, clinical studies with the agent have included patients regardless of baseline anemia and thrombocytopenia. As such, another analysis was conducted, pooling the results of the PERSIST-1 and PERSIST-2 trials, to determine dosing patterns and efficacy outcomes by degree of baseline cytopenia.

Results showed that patients maintained median dose intensity of 100% regardless of whether they had baseline platelet counts below or above 100 x 109/L or baseline hemoglobin levels below 8 g/dL, between 8 g/dL and 10 g/dL, or 10 g/dL or above.

Additionally, between 21% and 28% of all patients, regardless of platelet and hemoglobin levels, achieved SVR of at least 35%; between 39% and 44% of patients achieved SVR of at least 25%; between 75.5% and 82% achieved SVR of at least 10%; and between 84% and 93% of patients achieved any spleen volume reduction. Moreover, the depth of the 24-week spleen reduction was similar across all platelet and hemoglobin strata.

Similarly, all patients achieved spleen reduction by week 12, and SVR remained consistent over time across all subgroups. Median hemoglobin also remained stable through week 24 across all hemoglobin thresholds, though some improvement was reported in patients with baseline levels below 8 g/dL.

Any improvement in total symptom score (TSS) was documented in between 80% and 87.5% of patients across all cytopenic groupings, although most patients with baseline hemoglobin below 8 g/dL (62.5%) derived the greatest magnitude in symptom improvement (TSS ≥50). Notably, 12-week TSS improvement occurred with deepening improvement through week 36, particularly in patients with baseline hemoglobin below 8 g/dL.

Regarding Patient Global Impression of Change response across all baseline blood count strata, approximately 80% of patients reported clinical improvement in disease symptoms and approximately 50% of patients classified their symptoms as “much” or “very much” improved at week 24.

“[This study] takes a look at the totality of the pacritinib data across doses across levels of cytopenias among patients and shows that while this drug is best known for its efficacy in cytopenic patients, it shows that the efficacy is about the same in those with higher blood counts as well, or at least it is certainly preserved in those patients as well,” Prithviraj Bose, MD, associate professor in the Department of Leukemia, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center in Houston, told Oncology Nursing News®.


  1. Ajufo H, Bewersdorf JP, Harrison C, et al. Spleen volume reduction (SVR) predicts overall survival (OS) in myelofibrosis (MF) patients on pacritinib (PAC) but not best available therapy (BAT): PERSIST-2 landmark OS analysis. J Clin Oncol. 2023;41(suppl 16):7018. doi:10.1200/JCO.2023.41.16_suppl.7018
  2. Bose P, Gagelmann N, Gupta V, et al. Consistency of pacritinib for spleen and symptom reduction in patients with myelofibrosis regardless of cytopenias. J Clin Oncol. 2023;41(suppl 16):7068. doi:10.1200/JCO.2023.41.16_suppl.7068
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