Post-Approval Utilization of Pacritinib and Momelotinib in Patients with Myelofibrosis and Analysis of Early Treatment Outcomes

Introduction

Pacritinib (PAC) and momelotinib (MMB) have recently been approved for myelofibrosis (MF). Both agents target patients with cytopenic MF, with PAC approved for platelets < 50 x 10⁹/L and MMB for patients with MF and anemia. There is sizable overlap in efficacy profiles as both show the ability to improve spleen volume and disease-related symptoms while favorably impacting anemia and thrombocytopenia in a subset of patients. Optimal selection of PAC or MMB in cytopenic MF has not been well-defined. Direct comparison within the context of a clinical trial is lacking. Therefore, we analyzed patients treated with PAC and/or MMB since their respective FDA-approvals to characterize the profiles with each agent, early impact on hematologic values, and the overall outcomes.

Methods

We analyzed the first 50 patients who were treated at Moffitt Cancer Center with PAC or MMB. Treatment history, demographic, hematologic, and genetic information was obtained. Hematologic values and transfusion requirements were assessed every 3 months (+/- 1 month). Baseline values, change in blood counts over time, and treatment duration was compared between PAC and MMB-treated patients. T-tests and chi-square analysis were utilized for statistical analyses.

Results

Among 50 patients who received commercial PAC and/or MMB, 32 received MMB, 27 received PAC and 9 received both.

At baseline, patients receiving PAC had a median age of 77 years (y), median disease duration of 3.7 y, and received a median of 2.5 prior lines of therapy. High-risk mutations (HMR) were present in 14/27 (52%). MMB-treated patients had a median age of 75.5 y, median disease duration of 6.5 y, and a median of 2 prior lines of therapy. HMR were present in 15/32 (47%) patients. None of these variables were significantly different between the two agents.

At baseline, PAC-treated patients had median hemoglobin (hgb) and platelet (plt) count of 8.5g/dL (6.9-12.9g/dL) and 65 x 10⁹/L (18-441 x 10⁹/L), respectively. 8/27 (30%) were transfusion dependent (≥4 units RBCs/prior 8 weeks), 18/27 (67%) were transfusion-requiring with an average of 2.4 units/month. 21/27 (78%) had splenomegaly with median spleen length below left costal margin (LCM) of 7.5 cm. MMB-treated patients had baseline hgb and plt count of 8.7 g/dL (6.5-1.2 g/dL) and 141 x 10⁹/L (15-504 x 10⁹/L), respectively. 7/32 (22%) were transfusion-dependent, 19/32 (59%) were transfusion-requiring with an average of 1.9 units/month. 23/32 (75%) had splenomegaly with median spleen length below the LCM of 6 cm. PAC-treated patients had significantly lower baseline plt count than MMB-treated patients (p = 0.04).

8 patients (30%) treated with PAC had hematologic values at 3 months (mo). At this time, median hgb and plt count was 9.1 g/dL and 31 x 10⁹/L, respectively. Average transfusion requirements decreased to 0.75 units/month. 23 (72%) patients treated with MMB had hematologic values at 3 mo. At this time hgb and plt count was 9.0 g/dL and 116 x 10⁹/L. Average transfusion requirements decreased to 0.47 units/month.

In patients treated with MMB, hgb increase from baseline to 3 mo was more marked in those patients who were transitioning from ruxolitinib to MMB compared to patients with no recent ruxolitinib use (≤ 2 mo prior to MMB) (Δhgb 1.42 g/dL vs. 0.42 g/dL).

Median duration of treatment with PAC was 3.3 mo. Common reasons for discontinuation were GI toxicity (n = 7) and death (n = 6). Median duration of treatment with MMB was 8.2 mo. Common reasons for discontinuation were non-heme/non-GI toxicity (n = 7) and thrombocytopenia (n = 3). Differences in duration of treatment with PAC and did not reach statistical significance (p = 0.07).

Overall survival (OS) was longer in MMB-treated patients compared to PAC-treated patients with 6-month / 9-month OS of 73% / 64% with PAC vs. 96% / 96% with MMB (p = 0.037).

Conclusions

PAC and MMB are used in overlapping, high-risk patient populations. These patients are typically older, with extended disease duration, multiple prior lines of therapy, high-risk mutations, and have significant cytopenias. As expected, PAC-treated patients had more prominent baseline thrombocytopenia. Favorable impacts on anemia and transfusion requirements were shown with both PAC and MMB though long-term follow-up is limited. Ongoing evaluation in a large, multi-center, real world database of PAC and MMB-treated patients may help optimize treatment selection in patients with cytopenic MF.

Chan:AbbVie: Honoraria, Research Funding; Aptitude Health: Honoraria; Syndax: Membership on an entity's Board of Directors or advisory committees; Jazz: Research Funding; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Lancet:Prelude Therapeutics: Consultancy, Other: Bristol Myers Squibb; Bristol Myers Squibb: Consultancy, Other: Consultant/Advisory Board; Tradewell Therapeutics: Consultancy, Other: Consultant/Advisory Board. Sallman:Agios: Consultancy; Abbvie: Consultancy; Axiom: Consultancy; Gilead: Consultancy; Celyad: Consultancy; Froghorn: Consultancy; Incyte: Consultancy; Intellisphere, LLC: Consultancy; Johnson & Johnson: Consultancy; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Magenta Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; NextTech: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; AvenCell: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; BlueBird Bio: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Dark Blue Therapeutics: Membership on an entity's Board of Directors or advisory committees; Intellia: Membership on an entity's Board of Directors or advisory committees; Jasper Therapeutics: Membership on an entity's Board of Directors or advisory committees; NKARTA: Membership on an entity's Board of Directors or advisory committees; Orbital Therapeutics: Membership on an entity's Board of Directors or advisory committees; Rigel Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Shattuck Labs: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Syndax: Membership on an entity's Board of Directors or advisory committees; Syros: Membership on an entity's Board of Directors or advisory committees; Apera: Research Funding; Jazz: Research Funding. Kishtagari:Sevier Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Geron Coporation: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees; Rigel: Membership on an entity's Board of Directors or advisory committees; Sobi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Syndex: Current equity holder in publicly-traded company. Vachhani:MorphoSys: Consultancy; Pfizer: Consultancy; Stemline: Consultancy; Karyopharm: Consultancy; Daiichi Sankyo: Consultancy; Gilead/Forty Seven: Research Funding; Constellation Pharmaceuticals: Research Funding; Takeda: Research Funding; Kartos Therapeutics: Research Funding; Seattle Genetics: Research Funding; Astex Pharmaceuticals: Research Funding; Novartis: Consultancy; GlaxoSmith Kline: Consultancy; GenenTech: Consultancy; CTI BioPharma Corp (now Sobi): Consultancy, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cogent Biosciences: Consultancy; Amgen: Consultancy, Research Funding; Blueprint Medicines: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Mascarenhas:AbbVie: Consultancy, Research Funding; Ariad: Speakers Bureau; Pfizer: Research Funding; PharmaEssentia: Consultancy, Research Funding; Kartos: Consultancy, Research Funding; MorphoSys: Consultancy; Disc: Consultancy; GSK: Consultancy; Roche: Consultancy; Karyopharm: Consultancy; Geron: Consultancy, Research Funding; Sumitomo: Consultancy; Blueprint Medicines: Consultancy; Novartis: Consultancy, Other: Travel Support , Research Funding, Speakers Bureau; Keros: Consultancy; Ajax: Research Funding; Merck: Consultancy; Icahn School of Medicine at Mount Sinai: Current Employment; CTI BioPharma/SOBI: Consultancy, Research Funding; Celgene: Consultancy, Other: Travel Support, Speakers Bureau; Bristol Myers Squibb: Research Funding; NS Pharma: Research Funding; Incyte Corporation: Consultancy, Speakers Bureau; Astellas: Research Funding. Komrokji:DSI: Honoraria, Membership on an entity's Board of Directors or advisory committees; PharmaEssentia: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Genentech: Consultancy; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servio: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; DSI: Consultancy, Membership on an entity's Board of Directors or advisory committees; Rigel: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Taiho: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; CTI biopharma: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Keros: Membership on an entity's Board of Directors or advisory committees; Sobi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene/BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sumitomo Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Geron: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servio: Honoraria; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Kuykendall:PharmaEssentia: Honoraria; Protagonist Therapeutics: Honoraria, Research Funding; Incyte: Honoraria; Novartis: Research Funding.