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Combining Ruxolitinib and Supportive Anemia Care Enhances Myelofibrosis Treatment

Key Takeaways

  • Anemia affects 35%-54% of myelofibrosis patients, complicating treatment and impacting survival outcomes.
  • Ruxolitinib, a JAK1/JAK2 inhibitor, is first-line for MF but can exacerbate anemia, necessitating additional management strategies.
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The data support the use of supportive anemia care agents in combination with ruxolitinib (Jakafi; Incyte Corp).

Anemia is a highly prevalent complication associated with myelofibrosis, affecting nearly 35% to 54% of patients at diagnosis. Clinical guidelines recommend use of erythropoiesis-stimulating agents (ESAs) and danazol (Danocrine; Sanofi-Synthelabo Inc) to manage anemia; however, there are little data regarding clinical outcomes of these agents in combination with ruxolitinib (Jakafi; Incyte Corp). Data from a post hoc analysis of the phase 3 JUMP trial (NCT01493414) will be presented at the 66th ASH Annual Meeting and Exposition on December 9, 2024.1,2

AI concept of red blood cells | Image Credit: © loran4a - stock.adobe.com

AI concept of red blood cells | Image Credit: © loran4a - stock.adobe.com

MF is characterized by the overproduction of hematopoietic stem cells and increasingly reduced red blood cell production. The resulting bone marrow fibrosis leads to severe anemia, which greatly impacts overall survival outcomes. The Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib is first-line treatment for MF, but it is strongly associated with the development of dose-dependent anemia or the worsening of existing anemia.1,3

The primary therapeutic options for patients with MF managing anemia are red blood cell transfusions, ESAs, and danazol, an anabolic steroid medication. However, there are little data supporting the safety and efficacy of using these agents in combination with ruxolitinib for patients with MF and anemia. In an analysis of findings from the JUMP trial, researchers aimed to better understand the clinical outcomes of patients treated with ruxolitinib who initiate anemia management with ESAs or danazol.3,4

The single-arm, multicenter, expanded access, phase 3 JUMP trial is the largest ruxolitinib trial as of 2024 and evaluated the safety and efficacy of ruxolitinib plus ESAs or danazol in a population of 2233 patients with MF. The study population included patients 18 years or older with primary or secondary MF and baseline platelet ≥50×109/L, which determined the starting dose of 5 to 20 mg twice daily of ruxolitinib.1,3

In the post hoc analysis, the researchers assessed patients with baseline anemia (hemoglobin [Hb] <12.0 g/dL or Hb <10.0 g/dL) who were not receiving supportive care for anemia but initiated an ESA or danazol within 3 months of enrollment, remaining on the treatment for ≥3 months. The primary end points to determine the safety and efficacy of ruxolitinib in combination with anemia managing therapies were spleen length response (SLR; ≥50% reduction from baseline) and symptom response (≥6.5-point increase in Functional Assessment of Cancer Therapy–Lymphoma total score from baseline).3

The researchers divided 1384 patients who were not receiving anemia care at trial enrollment into 2 cohorts based on Hb levels: Hb<12.0 g/dL (n=629) and Hb<10.0 g/dL (n=755). Ruxolitinib was administered to patients with Hb<12.0 g/dL at a mean total daily dose of 35 mg compared with 34 mg in the Hb<10.0 g/dL arm. Both cohorts decreased to 25 mg through weeks 45 to 48.3

Of the patients with Hb<12.0 g/dL, 101 (7.3%) initiated an ESA (n=98) or danazol (n=3) within 3 months of enrollment (52 [6.9%] with Hb<10.0 g/dL), with a median time from enrollment to first dose of an ESA or danazol of 43 days.3

In the Hb<12.0 g/dL arm, the median age was 70 years old (54% male) with a MF duration since diagnosis of 19 months. The median age of patients in the Hb <10.0 g/dL arm was 72, of which 52% were male with a median MF duration since diagnosis of 13 months. The median time from enrollment to first dose of an ESA or danazol was 34 days.3

Of all the participants, 91% and 89% had a palpable spleen in the Hb<12.0 g/dL and Hb<10.0 g/dL arms, respectively. At week 12, the data showed that both patient groups achieved SLR rates of 42%, which decreased to 34% in patients with Hb <12.0 g/dL) and 29% in patients with Hb <10.0 g/dL at week 24.3

Mean Hb levels in the Hb<12.0 g/dL arm was 9.9 g/dL at baseline, which reached a nadir at week 4 (8.9 [1.3] g/dL) and steadily increased to week 48 (9.9 [1.5] g/dL; mean 1.5% change from baseline). Similar results were observed in patients with Hb <10.0 g/dL who achieved a mean Hb of 9.1 g/dL at baseline, a nadir of 8.3 g/dL at week 4 and 9.5 g/dL at week 48 (mean 6.5% change from baseline).3

Patients with Hb<12.0 g/dL required a mean 0.8 transfusions in the 8 weeks before baseline (n=101), 1.3 in weeks 17 to 24 (n=63), and 0.5 in weeks 41 to 48 (n=46). The Hb <10.0 g/dL arm saw slightly higher transfusion requirement means of 1.0 at week 8, 1.7 from weeks 17 to 24, and 0.6 from weeks 41 to 48.3

These findings highlight the efficacy and safety of ESA or danazol treatment in managing anemia among patients with lower Hb levels, demonstrating improvement in spleen length reduction, symptom response, and Hb trends over time. The results reinforce the significance of offering patients with MF and anemia with supportive anemia care.

REFERENCES
1. Patients with anemia and myelofibrosis have worse survival outcomes when treated with ruxolitinib. Pharmacy Times. December 2, 2024. Accessed December 2, 2024. https://www.pharmacytimes.com/view/real-world-analysis-shows-anemia-worsens-survival-in-myelofibrosis
2. Inc424 for patients with primary myelofibrosis, post polycythemia myelofibrosis or post-essential thrombocythemia myelofibrosis. (jump). ClinicalTrials.gov Identifier: NCT01493414. Updated April 26, 2019. Accessed December 4, 2024. https://clinicaltrials.gov/study/NCT01493414
3. Vachhani P, Repp J, Hamer- Maansson JE, et al. 4546 clinical outcomes in patients with myelofibrosis treated with ruxolitinib and anemia-supporting medications. Presented at: 66th ASH Annual Meeting and Exposition. December 9, 2024. San Diego, CA. Abstract 4546.
4. Verstovsek S. How i manage anemia related to myelofibrosis and its treatment regimens. Ann Hematol. February 14, 2023. doi:10.1007/s00277-023-05126-4