The mpn Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the mpn Hub cannot guarantee the accuracy of translated content. The mpn and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.
The MPN Hub is an independent medical education platform, sponsored by AOP Health and GSK, and supported through an educational grant from Bristol Myers Squibb. The funders are allowed no direct influence on our content. The levels of sponsorship listed are reflective of the amount of funding given. View funders.
Now you can support HCPs in making informed decisions for their patients
Your contribution helps us continuously deliver expertly curated content to HCPs worldwide. You will also have the opportunity to make a content suggestion for consideration and receive updates on the impact contributions are making to our content.
Find out more
Create an account and access these new features:
Bookmark content to read later
Select your specific areas of interest
View mpn content recommended for you
MANIFEST-2: Primary analysis of pelabresib plus ruxolitinib in JAKi-naïve patients with MF
|
There remains an unmet need for novel treatment combinations for patients with MF due to the limited depth and durability of response and frequent TEAEs associated with JAKi monotherapy.1 The primary analysis from the phase III MANIFEST-2 trial (NCT04603495) evaluating the efficacy and safety of BET inhibitor pelabresib + ruxolitinib vs ruxolitinib + placebo in JAKi-naïve patients with MF was published in Nature Medicine by Rampal et al.1 Among all patients (N = 430), 214 were treated with pelabresib + ruxolitinib and 216 were treated with placebo + ruxoltitinib.1 The primary endpoint was splenic response at Week 24 and key secondary endpoints included absolute change in TSS and TSS50 at Week 24.1 |
| Key learnings |
| The primary endpoint of reduction in SV35 at Week 24 was met in 65.9% vs 35.2% (difference, 30.4%; 95% CI, 21.6–39.3; p < 0.001) of patients in the pelabresib + ruxolitinib vs ruxolitinib + placebo groups, respectively. |
|
At Week 24, the absolute change in TSS was −15.99 vs −14.05 (difference, (−1.94; 95% CI, −3.92 to 0.04; p = 0.0545) and TSS50 was achieved in 52.3% vs 46.3% (difference, 6.0%; 95% CI -3.5–15.5) of patients in the pelabresib + ruxolitinib vs ruxolitinib + placebo groups, respectively. |
| Grade ≥3 TEAEs were lower for pelabresib-treated patients (49.1% vs 57.0%). Any grade thrombocytopenia (52.8% vs 37.4%) and anemia (44.8% vs 55.1%) were the most frequent hematologic TEAEs in the pelabresib + ruxolitinib vs ruxolitinib + placebo groups, respectively. |
|
These findings highlight the potential of pelabresib + ruxolitinib as a first-line combination therapy for JAKi-naïve patients with MF, offering disease modification and a substantial clinical benefit vs SoC JAKi monotherapy, while maintaining a manageable safety profile. |
Abbreviations: BET, bromodomain and extraterminal; CI, confidence interval; JAKi, Janus kinase inhibitor; MF, myelofibrosis; SoC, standard of care; SVR35, spleen volume reduction ≥35%; TEAE, treatment-emergent adverse event; TSS, total symptom score; TTS50, total symptom score ≥50%.
References
Please indicate your level of agreement with the following statements:
The content was clear and easy to understand
The content addressed the learning objectives
The content was relevant to my practice
I will change my clinical practice as a result of this content
