Novel therapies and pitfalls in MPN

KRT-232 demonstrates a dose-dependent relationship for safety and efficacy and shows promising activity and tolerability in poor prognosis R/R MF pts. Of note, magnitude of SVR may have been confounded by a lack of Rux washout and the timing of BLS relative to initiation of KRT-232. This is the first clinical proof-of-concept highlighting the important role of MDM2i for the treatment of R/R MF. Recommended dose and schedule for Part B is KRT-232 240 mg d 1-7/28-d cycle.
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Abdulraheem Yacoub, Eunice S. Wang, Raajit K. Rampal, et al.
 
The authors of the abstract conclude: 
Addition of parsaclisib to RUX showed efficacy in pts with MF experiencing suboptimal response. QD parsaclisib dosing appeared to be more efficacious than QD/QW. Combination therapy demonstrated an acceptable safety profile with limited Gr 3/4 TEAEs and no dose-limiting TEAEs. Pt enrollment continues; updated data will be presented.
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Francesca Palandri, Giuseppe Alberto Palumbo, Elena Maria Elli, et al.
 
The authors of the abstract conclude: 
Severe RDS is very rare (<1% of pts), but symptoms and/or splenomegaly significantly increase in >20% of pts after RUX stop. Pts at higher risk for RDS, particularly those whose discontinuation is forced by AEs, should be followed more cautiously. Also, RDS may identify a population that can still benefit from RUX rechallenge because the rebound indicates residual disease control activity (i.e. those suspended intentionally for apparent loss of efficacy). Overall, these results highlight the need for implementation of active prevention strategies and suggest a quick switch to alternative treatment if clinically indicated.
 
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Naveen Pemmaraju, Vikas Gupta, Haris Ali, et al.
 
The authors of the abstract conclude: 

We have demonstrated clinical benefit of TAG monotherapy, with predictable and manageable safety in poor-risk MF patients. One patient developed CLS grade 3. The study cohort has recently been expanded. NCT02268253.

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Florence Roufosse, Jean-Emmanuel Kahn, Gerald J. Gleich, et al.
 
The authors of the abstract conclude: 
Mepolizumab reduced the occurrence of flares compared with placebo, with no unexpected safety signals identified. This suggests that patients with relapsing HES may benefit from mepolizumab treatment.

 

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