The use of erythropoiesis‐stimulating agents is safe and effective in the management of anaemia in myelofibrosis patients treated with ruxolitinib

Crisà, Elena; Cilloni, Daniela; Elli, Elena Maria; Martinelli, Vincenzo; Palumbo, Giuseppe A.; Pugliese, Novella; Beggiato, Eloise; Frairia, Chiara; Cerrano, Marco; Lanzarone, Giuseppe; Marchetti, Monia; Mezzabotta, Mauro; Boccadoro, Mario; Ferrero, Dario

doi:10.1111/bjh.15450

Cited by 23 publications

(24 citation statements)

References 13 publications

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“…Consistent with the mechanism of action of JAK2 inhibitors, the main adverse effect of ruxolitinib is anemia, which is observed in ~40% of patients, and thrombocytopenia [136]. The use of erythropoiesis-stimulating agents (ESAs) in combination with ruxolitinib to alleviate anemia was initially discouraged in phase 3 COMFORT I study but some responses were seen in a post hoc analysis from COMFORT II patients [137].…”

Section: Combination Therapymentioning

confidence: 99%

“…The use of erythropoiesis-stimulating agents (ESAs) in combination with ruxolitinib to alleviate anemia was initially discouraged in phase 3 COMFORT I study but some responses were seen in a post hoc analysis from COMFORT II patients [137]. In a recent multicenter study, ESAs in combination with ruxolitinib led to improvements in anemia in MF patients, with no associated toxicities and with a trend towards better survival [136]. Ruxolitinib has also been tested in combination with danazol, which has been used for the treatment of anemia in MF patients.…”

Section: Combination Therapymentioning

confidence: 99%

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Janus Kinases in Leukemia

Raivola

Haikarainen

Abraham

et al. 2021

Cancers

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Janus kinases (JAKs) transduce signals from dozens of extracellular cytokines and function as critical regulators of cell growth, differentiation, gene expression, and immune responses. Deregulation of JAK/STAT signaling is a central component in several human diseases including various types of leukemia and other malignancies and autoimmune diseases. Different types of leukemia harbor genomic aberrations in all four JAKs (JAK1, JAK2, JAK3, and TYK2), most of which are activating somatic mutations and less frequently translocations resulting in constitutively active JAK fusion proteins. JAKs have become important therapeutic targets and currently, six JAK inhibitors have been approved by the FDA for the treatment of both autoimmune diseases and hematological malignancies. However, the efficacy of the current drugs is not optimal and the full potential of JAK modulators in leukemia is yet to be harnessed. This review discusses the deregulation of JAK-STAT signaling that underlie the pathogenesis of leukemia, i.e., mutations and other mechanisms causing hyperactive cytokine signaling, as well as JAK inhibitors used in clinic and under clinical development.

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Section: Combination Therapymentioning

confidence: 99%

Section: Combination Therapymentioning

confidence: 99%

Janus Kinases in Leukemia

Raivola

Haikarainen

Abraham

et al. 2021

Cancers

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“…In a post-hoc analysis, McMullin et al reviewed the use of ESAs in patients receiving ruxolitinib in the COMFORT-II trial and demonstrated the combination was well tolerated, though rarely associated with a substantial benefit [ 51 ]. A subsequent retrospective analysis suggested a more favorable impact of adding ESA to ruxolitinib, with anemia responses occurring in 54% of patients, though the relative timing of ESA initiation to ruxolitinib varied [ 52 ]. While the concept of augmenting red blood cell production via stimulation of erythropoietin (EPO) receptors that are being blocked by downstream JAK2 inhibition seems illogical, ruxolitinib does not result in continuous JAK2 inhibition.…”

Section: Killing Two Birds With Two Stones: Efforts To Manage Anemmentioning

confidence: 99%

Finding a Jill for JAK: Assessing Past, Present, and Future JAK Inhibitor Combination Approaches in Myelofibrosis

Kuykendall

Horvat

Pandey

et al. 2020

Cancers

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Myelofibrosis (MF) is a myeloproliferative neoplasm hallmarked by the upregulation of the Janus kinase (JAK)—signal transducer and activator of transcription (STAT) pathway with associated extramedullary hematopoiesis and a high burden of disease-related symptoms. While JAK inhibitor therapy is central to the management of MF, it is not without limitations. In an effort to improve treatment for MF patients, there have been significant efforts to identify combination strategies that build upon the substantial benefits of JAK inhibition. Early efforts to combine agents with additive therapeutic profiles have given way to rationally designed combinations hoping to demonstrate clinical synergism and modify the underlying disease. In this article, we review the preclinical basis and existing clinical data for JAK inhibitor combination strategies while highlighting emerging strategies of particular interest.

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“…Crisà et al [34] retrospectively evaluated fifty-nine patients who received ruxolitinib combined with ESAs for anemia and had found that the rate of anemia may be related to the combination of ruxolitinib and ESAs, and lower erythropoietin (EPO) (< 125u/I) level was an obvious predictor of anemia response. Especially, there was no significant negative impact of the ESAs on response to ruxolitinib.…”

Section: Ruxolitinib Combined With Hydroxyurea Is Feasible In Real-womentioning

confidence: 99%

Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to

Zhu

Liu

et al. 2020

Ann Hematol

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Ruxolitinib is a targeted drug to treat myelofibrosis (MF). Ruxolitinib has significant advantages in spleen reduction and increasing 5-year overall survival (OS), and ruxolitinib-based combinations might provide more benefits than ruxolitinib monotherapy. In this review, we focus on the data of ruxolitinib-based combinations therapies and treatment-related adverse events (AEs) and safety. We analyzed and summarized the data of ruxolitinib-based combinations. Ruxolitinib combined with prednisone + thalidomide + danazol (TPD), panobinostat, pracinostat, azacytidine, or hydroxyurea has well reduced spleen. Ruxolitinib combined with danazol or TPD had well therapies in improvement of hemoglobin (Hgb) and platelets (PLT). Most ruxolitinibbased combinations therapies showed a superior benefit on reduced treatment-related AEs than ruxolitinib monotherapy. Treatment-related AEs and dose modification affect the safety and tolerability of ruxolitinib-based combinations. Genetic testing before treatment is recommended. To provide better clinical guidance, comparisons of these randomized controlled trials with the trials of ruxolitinib alone are necessary. This review suggests that the clinical application of ruxolitinib-based combinations is worth waiting for.

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The use of erythropoiesis‐stimulating agents is safe and effective in the management of anaemia in myelofibrosis patients treated with ruxolitinib

Cited by 23 publications

References 13 publications

Janus Kinases in Leukemia

Janus Kinases in Leukemia

Finding a Jill for JAK: Assessing Past, Present, and Future JAK Inhibitor Combination Approaches in Myelofibrosis

Ruxolitinib-based combinations in the treatment of myelofibrosis: worth looking forward to

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