Analysis of predictors of response to ruxolitinib in patients with myelofibrosis in the phase 3b expanded-access JUMP study

Gupta, Vikas; Grießhammer, Martin; Martino, Bruno; Foltz, Lynda; Tavares, Renato; Al-Ali, Haifa Kathrin; Giraldo, Pilar; Guglielmelli, Paola; Lomaia, Elza; Bouard, Catherine; Paley, Carole; Tiwari, Ranjan; Zor, Evren; Raanani, Pia

doi:10.1080/10428194.2020.1845334

Cited by 26 publications

(19 citation statements)

References 24 publications

(30 reference statements)

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“…Higher RUX dose intensity (≥/>10 mg BID or even more so ≥20 mg BID), especially at early time points, has previously been associated with better spleen response rates. 26,29,57 In turn, greater spleen length reductions under RUX are possibly correlated with improved survival. 17,19,27 Concerning the last risk factor identified, whereas anemia developed under RUX doesn't seem to negatively impact prognosis, the need for RBC transfusions is a well-known factor impacting survival in MF.…”

Section: Discussionmentioning

confidence: 99%

“…24,25 Pre-RUX factors associated with lower spleen response rates include higher risk MF, large splenomegaly, transfusion-dependency, platelet count <200 x10 9 /L, a time-interval between MF diagnosis and RUX start >2 years, RUX as ≥2 nd line treatment, any genotype other than JAK2V617F with ≥50% allele burden, and ≥3 mutations identified by next-generation sequencing (NGS). [26][27][28][29] Data on fatality after RUX discontinuation [30][31][32] collectively indicate the need for effective second line treatments.…”

Section: Number Of Figures and Tables: 5 (+ 7 As Supplementary Data)mentioning

confidence: 99%

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A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis

et al. 2022

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Ruxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most patients lose response over time and, after discontinuation, have a worse overall survival (OS). Currently, response criteria able to predict OS in RUX-treated patients are lacking, leading to uncertainty regarding the switch to second-line treatments. In this study, we investigated predictors of survival collected after six months of RUX in 209 MF patients participating in the real-world ambispective observational RUXOREL-MF study (NCT03959371). Multivariable analysis identified the following risk factors: (i) RUX dose <20 mg twice daily at baseline, month 3, and 6 (hazard ratio, HR, 1.79, 95% confidence interval, CI, 1.07-3.00, p=0.03), (ii) palpable spleen length reduction from baseline ≤30% at month 3 and 6 (HR 2.26, 95% CI 1.40-3.65, p=0.0009), (iii) red blood cell (RBC) transfusion need at month 3 and/or 6 (HR 1.66, 95% CI 0.95-2.88, p=0.07), and (iv) RBC transfusion need at all time points, i.e. baseline and months 3 and 6 (HR 2.32, 95% CI 1.19-4.54, p=0.02). Hence, we developed a prognostic model, named Response to Ruxolitinib after 6 months (RR6), dissecting three risk categories: low (median OS not reached), intermediate (median OS 61 months, 95% CI 43-80), and high (median OS 33 months, 95% CI 21-50). The RR6 model was validated and confirmed in an external cohort comprised of 40 MF patients. In conclusion, the RR6 prognostic model allows for the early identification of RUX-treated MF patients with impaired survival who might benefit from a prompt treatment shift.

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Section: Discussionmentioning

confidence: 99%

Section: Number Of Figures and Tables: 5 (+ 7 As Supplementary Data)mentioning

confidence: 99%

A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis

et al. 2022

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“…Ruxolitinib not only reduces spleen size but also improves the constitutional symptom burden [26]. However higher doses of ruxolitinib were associated with higher spleen response rates, but not with symptom improvement [31]. Low-dose ruxolitinib has been shown to be effective on constitutional symptoms [22].…”

Section: Discussionmentioning

confidence: 99%

Myelofibrozis hastalarında Ruxolitinib kullanımı: tek merkez deneyimi ve JAK-2 allel yükü ile Ruxolitinib yanıtı arasındaki ilişki

Göçer¹,

Kurtoğlu²

2020

Pamukkale Medical Journal

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Ruxolitinib is an oral JAK-1/2 inhibitor approved for the treatment of splenomegaly and/or constitutional symptoms in intermediate and high-risk myelofibrosis patients. The aim of our study is to evaluate the efficacy and safety of ruxolitinib in primary MF, post-ET MF and post-PV MF patients, to evaluate the relationship between response and JAK-2 allele burden and to compare them with literature data. Materials and methods: In our single centered and retrospective study, we investigated the data of 30 MF patients diagnosed in our clinic between May 2015 and December 2019. We reported demographic features, laboratory values, and spleen sizes. Results: 18 patients (60%) with a median age of 67.5 (45-78) had primary myelofibrosis. Spleen sizes decreased significantly 3 and 6 months after treatment. Constitutional symptoms have disappeared in 28 patients (93.3%). No association was found between JAK-2 allele burden and treatment response success. Conclusion: Ruxolitinib MF is very safe and effective to relieve constitutional symptoms and decrease spleen size. Despite JAK-2 inhibition, no linear relationship was found between JAK-2 allele burden and treatment efficacy.

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“…7 However, the same group of patients also has bet ter and more dura ble response with JAKi ther apy. 8,9 To our knowl edge, there is no pro spec tive study to com pare the out comes of HCT vs nontransplant ther apies in MF, and lim ited ret ro spec tive stud ies were either done in the pre-JAKi era or had a very small pro por tion of patients treated with JAKi. 7,10 Lack of com par a tive data in this area has led to sig nifi cant var i a tions in prac tice on appli ca tion of HCT in MF.…”

Section: Optimal Tim Ing Of Hct In Mf?mentioning

confidence: 99%

“…32,33 Initial tri als did not include patients with lower IPSS risk scores, and sub se quent stud ies have shown symp tom bene fit from ruxolitinib in a lower-risk pop u la tion. 8 Rates of spleen response cor re late with ruxolitinib dos ing, and cytopenias are the main dose-lim it ing tox ic ity. Other JAKi have been stud ied in phase 3 tri als with fedratinib approved by the US Food and Drug Administration for use in MF.…”

Section: Nontransplant Ther a Pies In Mf Splenomegaly And Con Sti Tu Tional Symp Tomsmentioning

confidence: 99%

Novel therapies vs hematopoietic cell transplantation in myelofibrosis: who, when, how?

England

Gupta

2021

Hematology

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Myelofibrosis is one of the classical Philadelphia chromosome–negative myeloproliferative neoplasms characterized by progressive marrow failure and chronic inflammation. Discovery of the JAK2 mutation paved the way for development of small molecular inhibitors and further facilitated the research in understanding of molecular biology of the disease. Development of novel medications and synergistic combinations with standard JAK inhibitor (JAKi) therapy may have the potential to improve depth and duration of disease control and symptomatic benefit, whereas advancements in allogeneic hematopoietic stem cell transplantation (HCT) have improved tolerability and donor availability, allowing for more patients to pursue this potentially curative therapy. The increase in options for medical therapy and changing risk profile of HCT is leading to increased complexity in counseling patients on choice of management strategy. In this case-based review, we summarize our approach to symptom-directed medical therapy, including the use of novel drugs and combination therapies currently under study in advanced clinical trials. We outline our recommendations for optimal timing of HCT, including risk-adapted selection for early HCT as opposed to delayed HCT after upfront JAKi therapy, as well as the use of pretransplant JAKi and alternative donor sources.

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Analysis of predictors of response to ruxolitinib in patients with myelofibrosis in the phase 3b expanded-access JUMP study

Cited by 26 publications

References 24 publications

A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis

A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis

Myelofibrozis hastalarında Ruxolitinib kullanımı: tek merkez deneyimi ve JAK-2 allel yükü ile Ruxolitinib yanıtı arasındaki ilişki

Novel therapies vs hematopoietic cell transplantation in myelofibrosis: who, when, how?

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