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Question 1 of 2
In the pelabresib + ruxolitinib arm at Week 24, what ≥35% reduction in spleen volume rate was observed?
A
B
C
D
Pelabresib, a bromodomain and extra-terminal motif inhibitor, is currently under investigation in Janus kinase inhibitor (JAKi) naïve patients with myelofibrosis (MF) as part of the phase III MANIFEST-2 trial (NCT04603495).1
This trial was selected by the MPN Hub Steering Committee as a top abstract at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition. Rampal presented the latest data from the MANIFEST-2 clinical trial of pelabresib + ruxolitinib for the treatment of JAKi-naïve myelofibrosis. Here, we summarize the key points.
Key eligibility criteria included:
At Week 24, the rate of SVR35, TSS50, and absolute change in symptom scores were recorded. Overall, the rate of SVR35 and TSS50 was higher in the experimental arm, with a higher mean spleen volume reduction (SVR) across the whole cohort (Figures 1 and 2).
Figure 1. SVR35 and TSS50 at Week 24*
SVR35, ≥35% reduction in spleen volume ; TSS50, ≥50% reduction in Total Symptom Score.
*Adapted from Rampal.1
Figure 2. Incidence of SVR35 and TSS50 in combination and isolation*
RUX, ruxolitinib; SVR35, ≥35% reduction in spleen volume ; TSS50, ≥50% reduction in Total Symptom Score.
*Adapted from Rampal.1
In each measure of TSS, pelabresib + ruxolitinib resulted in a larger mean change in symptom score from baseline to Week 24 (Figure 3). The highest recorded symptom decrease was observed in itching and pain under the left rib vs night sweats and pain under the left rib in the pelabresib arm vs the placebo arm, respectively.
Figure 3. Mean change in TSS by domain from baseline to Week 24*
RUX, ruxolitinib.
*Adapted from Rampal.1
Overall, the safety profile was comparable for the pelabresib and ruxolitinib alone groups (Table 1). A decreased incidence of anemia was observed, which is particularly beneficial for the treatment of MF where anemia is common.
Table 1. Treatment-emergent adverse events*
AE, adverse event; SAE, serious adverse event. |
||
Treatment-emergent adverse event, % (unless otherwise specified) |
Pelabresib + ruxolitinib |
Placebo + ruxolitinib |
---|---|---|
Any grade AE |
96.7 |
97.2 |
Grade ≥3 AE |
49.1 |
57.5 |
SAE |
29.7 |
29.4 |
Hematologic |
|
|
Anemia |
43.9 |
55.6 |
Thrombocytopenia |
32.1 |
23.4 |
Decreased platelet count |
20.8 |
15.9 |
Non-hematologic |
|
|
Diarrhea |
23.1 |
18.7 |
Dysgeusia |
18.4 |
3.7 |
Constipation |
18.4 |
24.3 |
Nausea |
14.2 |
15.0 |
Cough |
12.7 |
11.2 |
Fatigue |
11.8 |
16.8 |
Dizziness |
11.3 |
8.9 |
Headache |
11.3 |
10.7 |
COVID-19 |
11.3 |
15.9 |
Dyspnea |
9.0 |
13.1 |
Overall, treatment with pelabresib + ruxolitinib resulted in a higher incidence of SVR35 and significantly reduced splenomegaly in JAKi-naïve patients with MF compared with ruxolitinib + placebo. The combination also produced a significantly higher rate of dual SVR35 and TSS50, with a higher rate of improved individual symptom scores. The safety profile was comparable with ruxolitinib monotherapy, with a lower incidence of anemia. The results of MANIFEST-2 highlight pelabresib as a potential treatment option for JAKI-naïve MF for extended investigation in clinical trials.
References
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