Why peripheral neuropathy incidence is lower and cardiac toxicity is higher with carfilzomib when compared to bortezomib in multiple myeloma?
#mmsm
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#mmsm
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Peripheral neuropathy with proteosome inhibition:
❓likely caused by inhibition of a serine protease that is critical for neuronal cell survival called HtrA2/Omi
✅ carfilzomib has lower levels off-target protease inhibition (including activity at HtrA2/Omi protease)
❓likely caused by inhibition of a serine protease that is critical for neuronal cell survival called HtrA2/Omi
✅ carfilzomib has lower levels off-target protease inhibition (including activity at HtrA2/Omi protease)
❓How common is peripheral neuropathy with bortezomib
IV, twice weekly initial dosing: 35% (>=G3 in 13%)>SC,twice weekly: >=G3 in 6%>SC weekly dosing (ex’s👇)
What about carfilzomib?
Initial trial (PX-171-003-A1)- FDA AA with single agent activity~24% (PN >=G3:1%)
IV, twice weekly initial dosing: 35% (>=G3 in 13%)>SC,twice weekly: >=G3 in 6%>SC weekly dosing (ex’s👇)
What about carfilzomib?
Initial trial (PX-171-003-A1)- FDA AA with single agent activity~24% (PN >=G3:1%)
❓How common are cardiac AEs with carfilzomib?
An excellent summary table @andrew02114 👇
Notice also the renal AEs
An excellent summary table @andrew02114 👇
Notice also the renal AEs
❓why cardiac toxicity is more common with carfilzomib compared to bortezomib?
Not very clear, maybe related to endothelial damage, or increased PP2A activity and inhibition of AMPKα/autophagy regulatory axes 👇(Efentakis et al Blood 2019)
Not very clear, maybe related to endothelial damage, or increased PP2A activity and inhibition of AMPKα/autophagy regulatory axes 👇(Efentakis et al Blood 2019)
Another nice summary table of cardiac AEs with carfilzomib 👇 (Waxman et al JAMA Onc 2018)
AEs are imp and need to watch for
End 🧵
AEs are imp and need to watch for
End 🧵
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