Evaluation of Ruxolitinib versus Best Available Therapy in Treating Primary Myelofibrosis

Objectives: Ruxolitinib is a Janus kinase inhibitor (JAK) that is approved for the treatment of myelofibrosis. The therapeutic protocol has changed after the introduction of Ruxolitinib. The aim of this study was to evaluate the effectiveness of Ruxolitinib and to compare it with best available therapy in patients with primary myelofibrosis. Methods: In this retrospective study, 72 patients with primary myelofibrosis were scrutinized in the period from 2012 to 2018 at Nanakali hemato-oncology teaching center, Erbil, Iraqi Kurdistan. The patients were divided into 2 cohorts, 26 of them were treated with Ruxolitinib and 46 others received best available therapy. The patients’ characteristics, their response to treatment, and the outcomes were evaluated. The efficacy of treatment in both arms was compared. Results: The majority our studied patients (46, 63.8%) were in the high and intermediate-2 risk groups according to international prognostic scoring system. At time of diagnosis, there were no noticeable differences in the clinical characteristics and laboratory data among the Ruxolitinib and best available treatment groups of patients. Ruxolitinib was found to be effective in reducing the size of spleen and improving the overall survival when compared to best available treatment group (p<0.001, p= 0.008 respectively). The patients’ performance state had a significant effect on the overall survival in both treatment groups (p=0.003). Conclusion: Ruxolitinib has a significant role in reduction of spleen size, and potentially affect the survival outcomes in patients with myelofibrosis. Keywords: Ruxolitinib, Myelofibrosis, Splenomegaly, Outcomes.

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POS1020 EFFICACY OF TOFACITINIB ON DACTYLITIS IN INDIVIDUAL DIGITS IN PATIENTS WITH ACTIVE PSORIATIC ARTHRITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.73 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 777.2-778

Author(s):

A. M. Orbai ◽

P. J. Mease ◽

P. Helliwell ◽

O. Fitzgerald ◽

M. Bdewi ◽

...

Keyword(s):

Psoriatic Arthritis ◽

Kinase Inhibitor ◽

Janus Kinase ◽

Research Support ◽

Two Phase ◽

Janus Kinase Inhibitor ◽

Treatment Groups ◽

Link Type ◽

Hands And Feet ◽

Post Hoc

Background:Dactylitis, a hallmark of psoriatic arthritis (PsA), is a uniformly diffuse and sometimes painful swelling of the fingers and/or toes.1 Up to 50% of patients (pts) with PsA may experience dactylitis;1,2 as such, dactylitis is an accepted domain of PsA that should be considered in treatment decisions.3 In PsA, dactylitis typically involves feet more than hands; dactylitic joints more frequently have erosive damage, compared with non-dactylitic joints.2 There remains a need for effective therapies to treat dactylitis in pts with PsA. Improvements in dactylitis have been associated with tofacitinib, an oral Janus kinase inhibitor for the treatment of PsA.4,5Objectives:To assess the effect of tofacitinib on dactylitis by location (hands/feet) and individual digit involvement in pts with PsA.Methods:These post hoc analyses used data pooled from two Phase 3 studies (12-month OPAL Broaden [NCT01877668];5 6-month OPAL Beyond [NCT01882439]4) in pts with active PsA treated with tofacitinib 5 mg twice daily (BID; approved dose; to Month [M] 6), tofacitinib 10 mg BID (to M6) or placebo (PBO; to M3); pts were treated continuously with a single conventional synthetic disease-modifying antirheumatic drug. Pts were categorised by the presence of dactylitis at baseline (BL) in the hands and/or feet. Endpoints included change from BL in Dactylitis Severity Score (DSS),6 the number of dactylitic digits and the proportion of pts with dactylitis in individual digits at M1, M3 and M6. Descriptive statistics were generated by visit and treatment arm.Results:Data were pooled from 373 pts with DSS >0 at BL. BL characteristics, including gender, age, race, body mass index, PsA duration, BL DSS and dactylitic digits count were similar across dactylitis groups and treatment groups, except for pts with dactylitis in both the hands and feet, who had higher DSS compared to those with dactylitis in the hands or feet only, likely due to having more dactylitic digits (data not shown). Regardless of location, pts treated with tofacitinib had cumulative improvements from BL to M6 in DSS (Figure 1a) and in the number of dactylitic digits (Figure 1b); improvements in DSS were greater at M1 and M3, compared with PBO. Pts treated with tofacitinib 10 mg BID typically had numerically greater improvements in DSS, compared with pts treated with tofacitinib 5 mg BID (Figure 1a). Most pts treated with tofacitinib experienced improvement of dactylitis across all fingers and toes (Figure 1c–f); mean dactylitis presence was ≤15% at M6 in pts treated with tofacitinib for all digits. Generally, at M1 and M3, fewer pts treated with tofacitinib had dactylitis in any digit, compared with PBO (Figure 1c–f).Conclusion:Among pts with pre-existing dactylitis, treatment with tofacitinib resulted in improvements in dactylitis in hands, feet, or both, and in all digits as early as M1, and up to M6.References:[1]Kaeley et al. Semin Arthritis Rheum 2018; 48: 263-273.[2]Brockbank et al. Ann Rheum Dis 2005; 64: 188-190.[3]Coates et al. Arthritis Rheumatol 2016; 68: 1060-1071.[4]Gladman et al. N Engl J Med 2017; 377: 1525-1536.[5]Mease et al. N Engl J Med 2017; 377: 1537-1550.[6]Helliwell et al. J Rheumatol 2005; 32: 1745-1750.Acknowledgements:Study sponsored by Pfizer Inc. Medical writing support was provided by Eric Comeau, CMC Connect, and funded by Pfizer Inc.Disclosure of Interests:Ana-Maria Orbai Consultant of: Eli Lilly, Novartis, Pfizer Inc, Grant/research support from: AbbVie, Eli Lilly, Horizon, Janssen, Novartis, Philip J Mease Speakers bureau: AbbVie, Amgen, Bristol-Myers Squibb, Celgene, Eli Lilly, Genentech, Janssen, Novartis, Pfizer Inc, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Grant/research support from: AbbVie, Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer Inc, Sun, UCB, Philip Helliwell Paid instructor for: Janssen, Novartis, Pfizer Inc, Consultant of: Eli Lilly, Oliver FitzGerald Speakers bureau: AbbVie, Janssen, Pfizer Inc, Consultant of: Bristol-Myers Squibb, Celgene, Eli Lilly, Janssen, Pfizer Inc, Grant/research support from: AbbVie, Bristol-Myers Squibb, Eli Lilly, Novartis and Pfizer Inc, Mohammed Bdewi Speakers bureau: AbbVie, Pfizer Inc, Dona Fleishaker Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Rajiv Mundayat Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, Pamela Young Shareholder of: Pfizer Inc, Employee of: Pfizer Inc.

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A patient with a germline GATA2 mutation and primary myelofibrosis

Blood Advances ◽

10.1182/bloodadvances.2020003401 ◽

2021 ◽

Vol 5 (3) ◽

pp. 791-795

Author(s):

Cyrill V. Rütsche ◽

Eugenia Haralambieva ◽

Veronika Lysenko ◽

Stefan Balabanov ◽

Alexandre P. A. Theocharides

Keyword(s):

Bone Marrow ◽

Kinase Inhibitor ◽

Bone Marrow Failure ◽

Primary Myelofibrosis ◽

Janus Kinase ◽

Janus Kinase Inhibitor ◽

Key Points

Key Points First description of a patient with a germline GATA2 mutation and diagnosis of primary myelofibrosis. Development of bone marrow failure on a Janus kinase inhibitor.

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Persistent foot ulcer due to ruxolitinib therapy for primary myelofibrosis

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155217697488 ◽

2017 ◽

Vol 24 (3) ◽

pp. 226-228 ◽

Cited By ~ 3

Author(s):

Michael Del Rosario ◽

Henry Tsai ◽

Constantin A Dasanu

Keyword(s):

Scientific Literature ◽

Kinase Inhibitor ◽

Wound Care ◽

Foot Ulcer ◽

Primary Myelofibrosis ◽

Janus Kinase ◽

Oral Agent ◽

Bone Marrow Fibrosis ◽

Janus Kinase Inhibitor ◽

Marrow Fibrosis

Primary myelofibrosis is characterized by bone marrow fibrosis, splenomegaly and presence of JAK-2 V617F mutation in more than 90% of patients. Ruxolitinib is a Janus kinase inhibitor used for the treatment of primary myelofibrosis. We describe herein a persistent foot ulcer development attributed to ruxolitinib therapy. We are unaware of any previous reports of this phenomenon in the scientific literature. A thorough examination of the lower extremities is perhaps necessary before initiating this oral agent. If ruxolitinib therapy cannot be safely discontinued, diligent wound care and a course of antibiotics are warranted.

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JAK2, Calr and MPL Mutation Status Predicts the Survival Outcome of Patients with Primary Myelofibrosis

Blood ◽

10.1182/blood.v124.21.1829.1829 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1829-1829

Author(s):

Uri Rozovski ◽

Taghi Manshouri ◽

Vilma Dembitz ◽

Ksenija Bozinovic ◽

Sherry Pierce ◽

...

Keyword(s):

Overall Survival ◽

Triple Negative ◽

Primary Myelofibrosis ◽

Risk Groups ◽

Survival Outcome ◽

Janus Kinase ◽

Survival Outcomes ◽

Rapid Progression ◽

Mutation Status ◽

Substitution Mutation

Abstract Background Patients with primary myelofibrosis survive for a median of 5-7 years after diagnosis. However, survival outcomes markedly vary; some patients experience rapid progression and others survive for 10 years or more. The international prognostic scoring system (IPSS) stratifies patients into 4 risk groups on the basis of clinical features (age and constitutional symptoms) and blood counts (hemoglobin, white blood cells, and the presence of circulating blasts). Most patients with primary myelofibrosis harbor mutually exclusive somatic mutations in 1 of 3 genes. In 60% of patients, a substitution mutation is detected in the Janus Kinase 2 (JAK2) gene (JAK2V617F). In another 30% of patients, a frameshift mutation is identified in the Calreticulin (CALR) gene. In 5% of patients, a substitution mutation is found in the gene that codes for the thrombopoietin receptor (MPL). Although patients with mutated CALR generally have more indolent disease than patients with JAK2V617F, the prognostic significance of harboring JAK2V617F is confounded by the observation that low JAK2V617F allele burden is associated with aggressive disease and shortened overall survival (OS) duration. Aim To develop a prognostic model based on the mutation status of the JAK2, CALR, and MPL genes and to determine whether JAK2, CALR, and MPLmutation status provides additional prognostic value to the IPSS. Patients and methods Bone marrow samples were collected and processed from 344 patients with primary myelofibrosis at The University of Texas MD Anderson Cancer Center between 2000 and 2013 (157 months), at the initial visit. All samples were screened for JAK2V617F and for exon9 deletion or insertion mutations in CALR. We used quantitative PCR to quantify the levels of wild-type and mutated JAK2 and determine the JAK2V617F burden. Patients who did not have a mutation in either gene (n = 73) were also screened for an exon10 substitution mutation in MPL. Results Of the 344 patients screened for JAK2V617F and mutations in CALR, 226 (66%) had JAK2V617F and 43 (13%) had mutations in CALR. Of the 75 patients who did not have JAK2 or CALR mutations, 16 (21%) had mutated MPL. In 59 patients (17%), we did not identify mutations in any of the genes (“triple negative”). In the 226 patients who harbored the JAK2V617F mutation, a cut-point of 50% dichotomized patients into those with a high JAK2V617F burden (≥50%) and a favorable survival outcome (median OS: 80 months, 95% confidence interval [CI]: 51-109 months) and those with a low JAK2V617F burden and an adverse survival outcome (median OS: 50 months, 95% CI: 40-60 months; Figure 1). Clinically, patients with a high JAK2V617F burden had larger spleens than those with a low JAK2V617Fburden (P < .0001). We then classified patients according to mutation status into 5 groups: mutated CALR, mutated MPL, high JAK2V617F burden, low JAK2V617F burden, or triple negative) and used mutation status and the IPSS to fit a multivariate model to predict OS. In this model, the IPSS and mutation status independently predicted OS, and as implicated by the higher p-value of the Wald chi-square test, the mutation status was a superior estimate of OS. On the basis of this analysis, patients were stratified according to mutation status into 3 groups with different survival outcomes. Patients had a favorable outcome if they harbored CALR or MPL mutations or if they had a high JAK2V617F burden (n = 170, OS: 104 months, 95% CI: 86-122 months). Patients who were triple negative had an intermediate survival outcome (n = 59, OS: 56 months, 95% CI: 35-77 months). Patients with a low JAK2V617F burden had an adverse outcome (n = 115, OS: 45 months, 95% CI: 38-52 months; Figure 2). The risk of transformation to acute myeloid leukemia was similar across groups except that patients with a low JAK2V617Fburden had a lower risk of transformation (hazard ratio = 0.27, 95% CI: 0.1-0.8). Conclusion On the basis of mutation status in JAK2, CALR, and MPL, we stratified patients into 3 groups with good (CALR or MPL mutation or high JAK2V617F burden), intermediate (triple negative), or adverse (low JAK2V617Fburden) survival outcomes. Our results indicate that prognostication based on mutation status is independent of and superior to the IPSS. Figure 1: Overall survival in patients with primary myelofibrosis with a high or low JAK2V617Fburden Figure 1:. Overall survival in patients with primary myelofibrosis with a high or low JAK2V617Fburden Figure 2: Overall survival in patients with primary myelofibrosis, stratified by mutation status into 3 risk groups Figure 2:. Overall survival in patients with primary myelofibrosis, stratified by mutation status into 3 risk groups Disclosures No relevant conflicts of interest to declare.

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Cementless bipolar hemiarthroplasty in a patient with PMF: a case report

Journal of Surgical Case Reports ◽

10.1093/jscr/rjz274 ◽

2019 ◽

Vol 2019 (11) ◽

Author(s):

Abdullah A Alturki ◽

Nayf A Alshammari ◽

Firas M Alsebayel ◽

Ali A Alhandi

Keyword(s):

Kinase Inhibitor ◽

Myeloproliferative Neoplasms ◽

Primary Myelofibrosis ◽

Janus Kinase ◽

Bipolar Hemiarthroplasty ◽

Myeloproliferative Disease ◽

Neck Of Femur ◽

Janus Kinase Inhibitor ◽

History Of ◽

Neck Of Femur Fracture

Abstract Myelofibrosis is a myeloproliferative disease that falls under a group of bone marrow malignancies known as myeloproliferative neoplasms. It manifests with splenomegaly, anemia, leukocytosis and, less commonly, bone pain. Ruxolitinib, Janus kinase inhibitor, has been shown to increase survival, to improve symptoms and has the potential to decrease osteosclerotic changes. Herein, we present a case of primary myelofibrosis (PMF) in a 60-year-old female who presented with 8-month history of progressive left hip pain and later was diagnosed with pathological neck of femur fracture that was treated with cementless hemiarthroplasty. In conclusion, the use of cementless implants in hip arthroplasty in the presence of PMF has shown to be an effective and safe choice.

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