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With emerging new drugs in myelofibrosis (MF), a robust and harmonized framework for defining the severity of anemia and response to treatment will enhance clinical investigation and facilitate inter-study comparisons. Accordingly, the lead authors on the 2013 edition of the International Working Group-European LeukemiaNet (IWG-ELN) response criteria in MF were summoned to revise their document with the intent to i) account for gender-specific differences in determining hemoglobin levels for eligibility criteria, ii) revise definition of transfusion-dependent anemia (TDA) based on current restrictive transfusion practices, and iii) provide a structurally simple and easy to apply response criteria that are sensitive enough to detect efficacy signals (minor response) and also account for major responses. The initial draft of the 2024 IWG-ELN proposed criteria was subsequently circulated around a wider group of international experts and their feedback incorporated. The proposed articles include new definitions for TDA (≥3 units in the 12 weeks prior to study enrollment) and hemoglobin thresholds for eligibility criteria (<10 g/dL for women and <11 g/dL for men). The revised document also provides separate (TDA vs. non-TDA) and graded (major vs. minor response) response criteria while preserving the requirement for a 12-week period of screening and observation on treatment.
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BACKROUND: Real-world, long-term survival outcomes of neoadjuvant, docetaxel-based therapy for esophageal and junctional adenocarcinoma are lacking. This study describes the long-term survival outcomes of patients with esophageal and junctional adenocarcinoma treated with neoadjuvant docetaxel-based chemotherapy and en bloc transthoracic esophagectomy. METHODS: A retrospective cohort analysis of a prospectively maintained database from a regional upper gastrointestinal cancer network in Quebec, Canada, was performed. From January 2007 to December 2021, all patients with locally advanced (cT3 and/or N1) esophageal/Siewert I/II adenocarcinoma treated with neoadjuvant DCFx3 (Docetaxel/Cisplatin/5FU) or FLOTx4 (5FU/Leucovorin/Oxaliplatin/Docetaxel) and transthoracic en bloc esophagectomy were identified. Postoperative, pathological, and survival outcomes were compared. RESULTS: Overall, 236 of 420 patients met the inclusion criteria. Tumor location was esophageal/Siewert I/Siewert II (118/33/85), most were cT3-4 (93.6%) and cN+ (61.0%). DCF and FLOT were used in 127 of 236 (53.8%) and 109 of 236 (46.2%). All neoadjuvant cycles were completed in 87.3% with no difference between the regimens. Operative procedures included Ivor Lewis (81.8%), left thoraco-abdominal esophagectomy (10.6%) and McKeown (7.6%) with an R0 resection in 95.3% and pathological complete response in 9.7% (DCF 12.6%/FLOT 6.4%, p = 0.111). The median lymph node yield was 32 (range 4-79), and 60.6% were ypN+. Median follow-up was longer for the DCF group (74.8 months 95% confidence interval [CI] 4-173 vs. 37.8 months 95% CI 2-119, p <0.001. Overall survival was similar between the groups (FLOT 97.3 months, 78.6-115.8 vs. DCF 92.9, 9.2-106.5, p = 0.420). CONCLUSIONS: Neoadjuvant DCF and FLOT followed by transthoracic en bloc resection are both highly effective regimens for locally advanced esophageal adenocarcinoma with equivalent survival outcomes despite high disease load.
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Adenocarcinoma , Neoplasias Esofágicas , Humanos , Docetaxel , Terapia Neoadjuvante/métodos , Estudos Retrospectivos , Esofagectomia/métodos , Estadiamento de Neoplasias , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Fluoruracila , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , CisplatinoRESUMO
Momelotinib, a small-molecule inhibitor of Janus kinase 1 and Janus kinase 2, has demonstrated efficacy in myelofibrosis patients with 300 mg, once-daily dosing. This open-label, non-randomized, phase 1/2 study evaluated the safety and therapeutic benefit of momelotinib with twice-daily dosing. A total of 61 subjects with primary myelofibrosis or post-polycythemia vera/post-essential thrombocythemia myelofibrosis with intermediate- or high-risk disease received momelotinib. A phase 1 dose escalation identified 200 mg twice daily as the optimal dose to be expanded in phase 2. The most frequent adverse events were diarrhea (45.9%), peripheral neuropathy (44.3%), thrombocytopenia (39.3%), and dizziness (36.1%), the latter primarily due to a first-dose effect. The response assessment according to the 2006 International Working Group criteria (≥8 weeks duration at any time point) demonstrated spleen response by palpation of 72% (36/50) and anemia response of 45% (18/40). Spleen response by magnetic resonance imaging obtained at 24 weeks was 45.8% (27/59) for all subjects and 54.0% (27/50) for those with palpable splenomegaly at baseline. The symptoms of myelofibrosis were improved in most subjects. Cytokine analysis showed a rapid decline in interleukin-6 with momelotinib treatment, and a slower reduction in other inflammatory cytokines. In the subgroup of subjects with the JAK2V617F mutation at baseline (n=41), momelotinib significantly reduced the allele burden by 21.1% (median) at 24 weeks. These results provide evidence of tolerability and a potential therapeutic activity of momelotinib for subjects that support further evaluation in ongoing, phase 3 randomized trials. (clinicaltrials. gov identifier:01423058).
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Benzamidas/administração & dosagem , Mielofibrose Primária/tratamento farmacológico , Inibidores de Proteínas Quinases/administração & dosagem , Pirimidinas/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Benzamidas/efeitos adversos , Benzamidas/farmacocinética , Biomarcadores , Esquema de Medicação , Feminino , Humanos , Janus Quinase 2/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Fenótipo , Mielofibrose Primária/diagnóstico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Retratamento , Resultado do TratamentoAssuntos
COVID-19/etiologia , Doenças Transmissíveis/etiologia , Transtornos Mieloproliferativos/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Policitemia Vera/complicações , Mielofibrose Primária/complicações , Estudos Prospectivos , Quebeque/epidemiologia , Fatores de Risco , Trombocitemia Essencial/complicaçõesRESUMO
INTRODUCTION: Some Janus kinase (JAK) inhibitors such as ruxolitinib and fedratinib do not address and may worsen anemia in patients with myelofibrosis. In these cases, the JAK inhibitor may be continued at a reduced dose in an effort to maintain splenic and symptom control, with supportive therapy and/or red blood cell (RBC) transfusions added to manage anemia. This post hoc descriptive analysis of the phase 3 SIMPLIFY-2 trial evaluated the relative benefits of this approach versus switching to the JAK1/JAK2/activin A receptor type 1 inhibitor momelotinib in patients for whom anemia management is a key consideration. METHODS: SIMPLIFY-2 was a randomized (2:1), open-label, phase 3 trial of momelotinib versus best available therapy (BAT; 88.5% continued ruxolitinib) in JAK inhibitor-experienced patients with myelofibrosis (n = 156). Patient subgroups (n = 105 each) were defined by either baseline (1) hemoglobin (Hb) of < 100 g/L or (2) non-transfusion independence (not meeting the criteria of no transfusions and no Hb of < 80 g/L for the previous 12 weeks); outcomes have been summarized descriptively. RESULTS: In both subgroups of interest, week 24 transfusion independence rates were higher with momelotinib versus BAT/ruxolitinib: baseline Hb of < 100 g/L, 22 (33.3%) versus 5 (12.8%); baseline non-transfusion independent, 25 (34.7%) versus 1 (3.0%). Mean Hb levels over time were also generally higher in both subgroups with momelotinib, despite median transfusion rates through week 24 with momelotinib being comparable to or lower than with BAT/ruxolitinib. Spleen and symptom response rates with momelotinib in these subgroups were comparable to the intent-to-treat population, while rates with BAT/ruxolitinib were lower. CONCLUSION: In patients with moderate-to-severe anemia and/or in need of RBC transfusions, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using anemia supportive therapies. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02101268.
Patients with the rare blood cancer myelofibrosis often experience symptoms such as tiredness, an increase in the size of their spleens (an organ involved in filtering the blood), and anemia (too few red blood cells). One type of treatment for myelofibrosis, called a Janus kinase (JAK) inhibitor, can help patients to feel better and reduce the size of their spleens, but some JAK inhibitors do not help with anemia and may make it worse. In those situations, patients may continue to take their JAK inhibitor but also receive another type of treatment, called an anemia supportive therapy, and may also receive red blood cell transfusions. This study compared 2 treatment approaches, continuing the JAK inhibitor ruxolitinib and adding an anemia supportive therapy and/or transfusions versus switching to another treatment called momelotinib, in 2 groups of patients from a clinical trial: (1) patients with levels of hemoglobin (a red blood cell protein) at the start of the trial that indicated that they had anemia, and (2) patients who were already receiving red blood cell transfusions at the start of the trial. In both groups, more patients did not need red blood cell transfusions anymore at week 24 with momelotinib, and their hemoglobin levels on average became higher over time. More patients also had improvements in spleen size and symptoms with momelotinib. Overall, outcomes were improved by switching to momelotinib rather than continuing ruxolitinib and using supportive therapies and/or red blood cell transfusions to treat anemia.
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Anemia , Inibidores de Janus Quinases , Nitrilas , Mielofibrose Primária , Pirazóis , Pirimidinas , Humanos , Pirimidinas/uso terapêutico , Nitrilas/uso terapêutico , Pirazóis/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/complicações , Anemia/tratamento farmacológico , Anemia/etiologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Inibidores de Janus Quinases/uso terapêutico , Benzamidas/uso terapêutico , Janus Quinase 1/antagonistas & inibidores , Transfusão de Eritrócitos/estatística & dados numéricos , Idoso de 80 Anos ou mais , Resultado do Tratamento , Janus Quinase 2/antagonistas & inibidoresRESUMO
Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF) and is recommended for patients with higher risk disease. However, there is a risk of early mortality, and optimal timing is unknown. JAK inhibitor (JAKi) therapy may offer durable improvement in symptoms, splenomegaly and quality of life. The aim of this multicentre, retrospective observational study was to compare outcomes of patients aged 70 years or below with MF in chronic phase who received upfront JAKi therapy vs. upfront HCT in dynamic international prognostic scoring system (DIPSS)-stratified categories. For the whole study cohort, median overall survival (OS) was longer for patients who received a JAKi vs. upfront HCT, 69 (95% CI 57-89) vs. 42 (95% CI 20-not reached, NR) months, respectively (p = 0.01). In patients with intermediate-2 and high-risk disease, median OS was 55 (95% CI 36-73) months with JAKi vs. 36 (95% CI 20-NR) months for HCT (p = 0.27). An upfront HCT strategy was associated with early mortality and difference in median OS was not observed in any risk group by 5 years of follow-up. Within the limitations of a retrospective observational study, we did not observe any benefit of a universal upfront HCT approach for higher-risk MF.
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Transplante de Células-Tronco Hematopoéticas , Inibidores de Janus Quinases , Mielofibrose Primária , Humanos , Qualidade de Vida , Transplante Homólogo , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , América do NorteRESUMO
Myeloproliferative neoplasms (MPNs) are a group of chronic hematologic malignancies that lead to morbidity and early mortality due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs and are used commonly to guide therapeutic decisions, including allogenic stem cell transplant, in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively examined in this population. We conducted a retrospective review of patients evaluated at eight Canadian centers for MPN patients diagnosed at ≤45 years of age. In total, 609 patients were included in the study, with median overall survival of 36.8 years. Diagnosis of prefibrotic or overt PMF is associated with the lowest OS and highest risk of AP/BP transformation. Thrombotic complications (24%), including splanchnic circulation thrombosis (9%), were frequent in the cohort. Mutations in addition to those in JAK2/MPL/CALR are uncommon in the initial disease phase in our AYA population (12%); but our data indicate they may be predictive of transformation to post-ET/PV myelofibrosis.
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Transtornos Mieloproliferativos , Policitemia Vera , Mielofibrose Primária , Trombocitemia Essencial , Trombose , Humanos , Adulto Jovem , Adolescente , Pessoa de Meia-Idade , Mielofibrose Primária/genética , Mielofibrose Primária/terapia , Policitemia Vera/genética , Trombocitemia Essencial/genética , Canadá/epidemiologia , Transtornos Mieloproliferativos/complicações , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/terapia , Trombose/genética , Janus Quinase 2/genética , Mutação , Calreticulina/genéticaRESUMO
OBJECTIVES: Haematology patients are more likely to receive high intensity care near end of life (EOL) than patients with solid malignancy. Previous authors have suggested indicators of quality EOL for haematology patients, based on a solid oncology model. We conducted a retrospective chart review with the objectives of (1) determining our performance on these quality EOL indicators, (2) describing the timing of level of intervention (LOI) discussion and palliative care (PC) consultation prior to death and (3) evaluating whether goals of therapy (GOT), PC consultation and earlier LOI discussion are predictors of quality EOL. METHODS: We identified patients who died from haematological malignancies between April 2014 and March 2016 (n=319) at four participating McGill University hospitals and performed retrospective chart reviews. RESULTS: We found that 17% of patients were administered chemotherapy less than 14 days prior to death, 20% of patients were admitted to intensive care, 14% were intubated and 5% were resuscitated less than 30 days prior to death, 18% of patients received blood transfusion less than 7 days prior to death and 67% of patients died in an acute care setting. LOI discussion and PC consultation occurred a median of 22 days (IQR 7-103) and 9 days (IQR 3-19) before death. Patients with non-curative GOT, PC consultation or discussed LOI were significantly less likely to have high intensity EOL outcomes. CONCLUSIONS: In this study, we demonstrate that LOI discussions, PC consults and physician established GOT are associated with quality EOL outcomes for patients with haematological malignancies.
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Ruxolitinib improves splenomegaly and other disease-related symptoms in patients with myelofibrosis, but over time, many patients lose this benefit. It is difficult to determine whether this is due to resistance or intolerance to the drug; thus, we have used the more inclusive term of ruxolitinib failure. The survival of patients with myelofibrosis after ruxolitinib failure is poor but varies significantly by the pattern of the failure, underlining the need for a clinically appropriate classification. In this review, we propose diagnostic guidance for early recognition of the pattern of ruxolitinib failure and we recommend treatment options. The most frequent patterns of ruxolitinib failure are loss or failure to obtain a significant reduction in splenomegaly or symptom response, and the development or persistence of clinically significant cytopenias. Ruxolitinib dose modification and other ancillary therapies are sometimes helpful, and splenectomy is a palliative option in selected cases. Stem-cell transplantation is the only curative option for these patterns of failure, but its restricted applicability due to toxicity highlights the importance of ongoing clinical trials in this area. Recent approval of fedratinib by the US Food and Drug Administration provides an alternative option for patients with suboptimal or loss of spleen response. The transformation of myelofibrosis to accelerated or blast phase is an infrequent form of failure with an extremely poor prognosis, whereby patients who are ineligible for transplantation have limited treatment options.
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Mielofibrose Primária , Crise Blástica , Canadá , Humanos , Nitrilas , Mielofibrose Primária/tratamento farmacológico , Pirazóis/efeitos adversos , Pirimidinas , Estados UnidosRESUMO
OBJECTIVE: To document the Mayo Clinic decades-long experience with myeloproliferative neoplasms (MPNs) and provide mature risk-stratified survival data and disease complication estimates. PATIENTS AND METHODS: All Mayo Clinic patients with World Health Organization-defined MPNs constituted the core study group and included those with polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). RESULTS: A total of 3023 consecutive patients (median age, 62 years; range, 18-96 years) were considered: 665 PV, 1076 ET, and 1282 PMF. From October 27, 1967, through December 29, 2017, 1631 deaths (54%), 183 leukemic transformations (6%), 244 fibrotic progressions (14%), and 516 thrombotic events (17%) were recorded. Median overall survival (OS) was 18 years for ET, 15 years for PV, and 4.4 years for PMF (P<.05 for all intergroup comparisons). Inferior survival was documented in patients with ET diagnosed more recently (post-1990) (P<.001), whereas survival data were time independent in PV and PMF. After conventional risk stratification, OS in low-risk ET and low-risk PV were superimposed (P=.89) but each differed significantly from that of age- and sex-matched controls (P<.001). Leukemia-free survival was similar for ET and PV (P=.22) and significantly worse with PMF (P<.001). Compared with ET, PV was associated with higher risk of fibrotic progression (P<.001). Thrombosis risk after diagnosis was highest in PV and lowest in PMF (P=.002 for PV vs ET; P=.56 for ET vs PMF; and P=.001 for PV vs PMF). CONCLUSION: This study provides the most mature survival and outcomes data in MPNs and highlights MPN subgroup risk categorization as key in appraising disease natural history. The OS was only marginally better in ET compared with PV, and PV displayed a higher risk of thrombosis and fibrotic progression.
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Policitemia Vera/mortalidade , Mielofibrose Primária/mortalidade , Trombocitemia Essencial/mortalidade , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
JAK2V617F-positive patients with essential thrombocythemia, as opposed to their mutation-negative counterparts, require lower doses of hydroxyurea (HU) for control of their platelet count. In the current study, we looked for predictors of HU response in 69 patients with primary myelofibrosis (PMF) and 56 with polycythemia vera (PV). JAK2V617F analysis was performed on bone marrow-derived DNA obtained at or near the time of diagnosis. HU response in PMF was associated with a shorter disease duration (P = 0.008), absence of previous therapy (P = 0.01), older age at diagnosis (P = 0.009), and presence of JAK2V617F (P = 0.02). On multivariable analysis, only the latter retained its significance (48% vs. 8% response in mutation positive vs. negative cases). In PV, JAK2V617F allele burden correlated directly with HU response (P = 0.05) and inversely with daily HU dose in responding patients (P = 0.02). The current study suggests that JAK2V617F presence identifies PMF patients who are likely to respond to HU therapy, and information on its allele burden helps in assigning the optimal starting dose in individual patients with PV.
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Hidroxiureia/uso terapêutico , Janus Quinase 2/genética , Mutação de Sentido Incorreto , Mutação Puntual , Policitemia Vera/enzimologia , Mielofibrose Primária/enzimologia , Adulto , Fatores Etários , Idoso , Alelos , Estudos de Coortes , Análise Mutacional de DNA , Resistência a Medicamentos/genética , Feminino , Humanos , Hidroxiureia/administração & dosagem , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Policitemia Vera/tratamento farmacológico , Policitemia Vera/genética , Mielofibrose Primária/tratamento farmacológico , Mielofibrose Primária/genética , Resultado do TratamentoAssuntos
Policitemia Vera/complicações , Policitemia/complicações , Trombose/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Policitemia/diagnóstico , Policitemia Vera/diagnóstico , Estudos Retrospectivos , Trombose/diagnóstico , Adulto JovemRESUMO
OBJECTIVES: To standardize diagnostic investigations for myeloproliferative neoplasms (MPNs) to increase homogeneity in patient care and to streamline diagnostic approaches in the most efficient and cost-effective manner. METHODS: The development of Canadian expert consensus recommendations for the diagnosis of MPNs began with a review of the following: clinical evidence, daily practice, existing treatment guidelines, and availability of diagnostic tools. Each group member was assigned a specific topic, which they discussed with the entire group during several consensus meetings. RESULTS: This document provides the Canadian MPN group's recommendations, proposed diagnostic algorithms, and background evidence upon which decisions were made. CONCLUSIONS: Standardization of diagnostic investigations will increase homogeneity in patient care and provide a foundation for future clinical research in this rapidly evolving therapeutic area. Streamlining diagnostic approaches in the most efficient and cost-effective manner will also result in significant cost saving for the health care system.
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Transtornos Mieloproliferativos/diagnóstico , Canadá , Análise Custo-Benefício , Humanos , Laboratórios Hospitalares , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/patologiaRESUMO
The current study of 153 subjects with both classic and atypical myeloproliferative disorders suggests that neutrophil polycythemia rubra vera-1 (PRV-1) over-expression is a non-specific feature of clonal myeloproliferation that displays significant correlation with leukocyte alkaline phosphatase score. These observations undermine the utility of the PRV-1 assay as a diagnostic test of additional value.
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Isoantígenos/análise , Glicoproteínas de Membrana/análise , Transtornos Mieloproliferativos/diagnóstico , Receptores de Superfície Celular/análise , Adulto , Idoso , Fosfatase Alcalina/análise , Ensaios Enzimáticos Clínicos , Feminino , Proteínas Ligadas por GPI , Humanos , Isoantígenos/genética , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , Neutrófilos/química , RNA Mensageiro/análise , Receptores de Superfície Celular/genéticaRESUMO
Percutaneous thoracic interventions are among the most common procedures in today's medical practice. From the simple placement of a pleural drain to the ablation of lung tumors, the advent of image guidance has revolutionized minimally invasive procedures and has allowed for the introduction of new techniques and widened the range of indications. It is therefore imperative to understand the complications associated with these interventions and their management. This article illustrates the common complications associated with these interventions and highlights the relative safety of these interventions.
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Polycythemia vera (PV) is a clonal stem cell disorder characterized by erythrocytosis and associated with burdensome symptoms, reduced quality of life, risk of thrombohemorrhagic complications, and risk of transformation to myelofibrosis and acute myeloid leukemia. The discovery of the JAK2 V617 mutation marked a significant milestone in understanding the pathophysiology of the disease and subsequently the diagnostic and therapeutic approaches. The current diagnostic criteria for PV are based on hemoglobin level and presence of the JAK2 V617 mutation. The treatment is geared toward prevention of thrombotic events, normalization of blood counts, control of disease-related symptoms, and potential prolongation of survival. Cytoreductive therapy is indicated in patients at increased risk of thrombosis. Hydroxyurea (HU) remains the most commonly used first-line cytoreductive therapy and is superior to phlebotomy in reducing risk of arterial and venous thrombosis. Interferon (IFN) is used either at failure of HU or in selected patients as first-line therapy. The results of pegylated IFN in phase 2 studies appear encouraging, with molecular responses occurring in some patients. Ongoing phase 3 studies of HU versus pegylated IFN will define the optimal first-line cytoreductive therapy for PV. A recent phase 3 trial has shown the superiority of the JAK1/2 inhibitor ruxolitinib in comparison to best available treatment in HU-intolerant or -resistant patients. The therapeutic landscape of PV is likely to change in the near future. In this report, we assess the potential impact of the changing landscape of PV management on daily practice.
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Antimetabólitos/uso terapêutico , Hidroxiureia/uso terapêutico , Policitemia Vera/tratamento farmacológico , Idoso , Antimetabólitos/efeitos adversos , Canadá , Quimioterapia Combinada , Humanos , Hidroxiureia/efeitos adversos , Pessoa de Meia-Idade , Policitemia Vera/diagnóstico , Prognóstico , Qualidade de Vida , Medição de RiscoRESUMO
Myelofibrosis (MF) is a clonal stem cell disorder characterized by cytopenias, splenomegaly, marrow fibrosis, and systemic symptoms due to elevated inflammatory cytokines. MF is associated with decreased survival. The quality of life of patients with MF is similar to other advanced malignancies. Allogeneic hematopoietic cell transplantation is a curative treatment, but is applicable to a minority of patients with MF. None of the conventional therapies are known to alter the natural history of the disease. Significant progress has been made in the last few years in the understanding of disease biology of MF. Discovery of the JAK2V617F mutation paved the way for drug discovery in MF, and the first JAK1/2 inhibitor, ruxolitinib, has been approved by FDA and Health Canada. Several other JAK1/2 inhibitors are at various stages of clinical development. As a consequence, the therapeutic landscape of MF is changing from a disease where no effective therapies existed to one with several novel treatment options on the horizon. In this report, we assess the changing therapeutic options for MF, and critically analyze the position of novel treatments in the current armamentarium.