Anemia Does Not Diminish Benefit With Ruxolitinib Treatment in Myelofibrosis

Haifa Kathrin Al-Ali, MD

The onset of new or worsening anemia following treatment induction with ruxolitinib (Jakafi) did not reduce the clinical benefit of the agent for patients with primary or secondary myelofibrosis, according to data from a post-hoc analysis of the phase 3b JUMP trial (NCT01493414) which were presented during the 2024 EHA Congress.¹

The median overall survival (OS) among baseline anemic patients with new or worsening anemia (n = 361) was 58.3 months (95% CI, 52.6-not evaluable [NE]) compared with NE (95% CI, 52.7-NE) in those without new or worsening anemia (n = 486; HR, 1.08; 95% CI, 0.77-1.51; P = .66). Similarly, patients who were baseline nonanemic with new or worsening anemia (n = 756) achieved a median OS of NE (95% CI, NE-NE) vs NE (95% CI, NE-NE) in those with no new or worsening anemia (n= 630; HR, 0.66; 95% CI, 0.45-0.99; P = .04).

In a poster presentation of the data, study authors noted that these findings were consistent with the results of a recent pooled data analysis of the phase 3 COMFORT-I (NCT00952289) and COMFORT-II (NCT00934544) studies, which both examined ruxolitinib for patients with myelofibrosis.

“Dose-dependent anemia is one of the adverse effects [AEs] of ruxolitinib therapy,” Haifa Kathrin Al-Ali, MD, lead study author, professor of hematology, and head of the Krukenberg Cancer Center, at the University Hospital Halle (Saale) in Germany, explained during the presentation. “A previous analysis of 2 phase 3 trials [showed that] new or worsening anemia did not diminish the clinical benefit of ruxolitinib therapy.”

“The objective of this current analysis was to validate these findings using data from JUMP, which is the largest trial [of ruxolitinib] in patients with myelofibrosis to date,” he explained.

JUMP is a global, single-arm expanded-access study that evaluated ruxolitinib treatment in patients with myelofibrosis in a setting comparable with routine clinical practice. In order to be eligible, patients needed to be at least 18 years old and have a diagnosis of primary or secondary myelofibrosis that is high, intermediate-2, or intermediate-1 risk according to International Prognostic Scoring System criteria. Patients with intermediate-1 risk disease must have palpable splenomegaly of at least 5 cm from the costal margin.

All patients received ruxolitinib twice daily at a starting dose of 5 mg for those with a platelet count of 50 x 109/L to less than 100 x 109/L; 15 mg for those with a platelet count of 100 x 109/L to 200 x 109/L; or 20 mg for those with a platelet count over 200 x 109/L. Patients were stratified in the post hoc analysis by baseline anemia and transfusion status, with nonanemic being defined as hemoglobin levels over 100 g/L; transfusion-requiring anemia was defined as hemoglobin levels less than 100 and having received at least 2 units of red blood cells over 8 weeks before the first dose of ruxolitinib; or non-transfusion-requiring anemia.

The primary end point of JUMP was safety. Secondary end points included percentage of participants with at least 50% reduction in spleen length, 5-year best overall response according to spleen length, and change in ECOG performance status from baseline to worst post-baseline up to 5 years.²

The baseline characteristics of the new/worsening anemia (n = 1117) and no new/worsening anemia (n = 1116) groups were generally well balanced; the median age was 68.0 years (range, 18-89) vs 66.0 years (range, 20-89), respectively, and the median time since initial diagnosis was 24.9 months (range, 0-456) vs 26.9 months (range, 0-444). Most patients in both groups had a palpable spleen (93.8% vs 93.1%), a median platelet count of at least 200 x 109/L (65.0% vs 60.2%), were nonanemic (67.7% vs 56.5%), and had a mean hemoglobin of at least 100 g/L (66.7% vs 56.0%). The median palpable spleen length at baseline was 12.0 cm (range, 1-40) vs 12.8 cm (range, 0.5-45), respectively.1

Additional data showed that, at week 24, evaluable baseline nonanemic patients in the new/worsening anemia group (n = 473) and the no new/worsening anemia group (n = 394) experienced a spleen length reduction of at least 50% at respective rates of 31.5% vs 31.2% (P = .93); these respective rates were 24.4% vs 27.9% (P = .49) and 25.0% vs 29.8% (P = .48) among patients with non-transfusion requiring anemia and transfusion-requiring anemia. In the with non-transfusion requiring anemia subgroup 127 patients experienced new/worsening anemia and 179 did not; these figures were 92 patients and 84 patients, respectively in the transfusion-requiring anemia subgroup.

At week 48, evaluable baseline nonanemic patients in the new/worsening anemia group (n = 289) and the no new/worsening anemia group (n = 257) experienced a spleen length reduction of at least 50% at respective rates of 35.6% vs 26.1% (P = .02); these respective rates were 29.6% vs 27.2% (P = .71) and 19.0% vs 33.3% (P = .10) among patients with non-transfusion requiring anemia and transfusion-requiring anemia. In the with non-transfusion requiring anemia subgroup 81 patients experienced new/worsening anemia and 103 did not; these figures were 58 patients and 45 patients, respectively in the transfusion-requiring anemia subgroup.

In terms of symptom response, at week 24, baseline nonanemic patients in the new/worsening anemia group (n = 618) and the no new/worsening anemia group (n = 530) achieved a minimum 6.5-point increase in FACT-Lym total score at respective rates of 34.5% vs 34.% (P = .86); these respective rates were 32.7% vs 29.6% (P= .52) and 41.7% vs 32.1% (P = .13) among patients with non-transfusion requiring anemia and transfusion-requiring anemia. In the with non-transfusion requiring anemia subgroup, 153 patients experienced new/worsening anemia and 243 did not; these figures were 120 and 109 patients, respectively in the transfusion-requiring anemia subgroup.

At week 48, baseline nonanemic patients in the new/worsening anemia group (n = 120) and the no new/worsening anemia group (n = 109) experienced a minimum 6.5-point increase in FACT-Lym total score at respective rates of 30.4% vs 23.3% (P = .02); these respective rates were 26.4% vs 27.6% (P = .84) and 34.2% vs 33.3% (P = .91) among patients with non-transfusion requiring anemia and transfusion-requiring anemia. In the with non-transfusion requiring anemia subgroup, 106 patients experienced new/worsening anemia and 156 did not; these figures were 79 and 66 patients, respectively in the transfusion-requiring anemia subgroup.

Among evaluable patients in the new or worsening anemia (n = 1033) and no new or worsening anemia group (n = 1000) received a median dose exposure of 12.2 months (range, 0.2-59.7) and 12.5 months (range, 0-58.1) with ruxolitinib, respectively.

“These results are consistent with those obtained from a previous pooled analysis from the 2 phase 3 COMFORT trials,” Al-Ali concluded. “These results from JUMP based on a broad patient population in a real-world setting, including those with platelet counts of less than 100 x 109/L and lower-risk patients with myelofibrosis, support the use of ruxolitinib in patients with myelofibrosis regardless of baseline anemia or the development of treatment-related anemia.”

References

1. Al-Ali HK, Guglielmelli P, JE Hamer-Maansson, Braunstein E, Gupta V. The impact of new or worsening anemia on clinical outcomes in 2233 patients with myelofibrosis treated with ruxolitinib: results from the expanded-access jump study. Presented at: 2024 European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. Abstract P1044.
2. INC424 for patients with primary myelofibrosis, post polycythemia myelofibrosis or post-essential thrombocythemia myelofibrosis. (JUMP). ClinicalTrials.gov. Updated April 26, 2019. Accessed June 14, 2024. https://clinicaltrials.gov/study/NCT01493414