A very relevant question given that it needs to be administered indefinitely.
41% discontinuation rate in the "real world", most d/t toxicity.
1. A fib
2. ⬆️ Risk of bleeding
3. ⬆️ Infections
⬆️A .fib = anticoag for stroke prophylax. but that's when tox no.2 comes into play.
Very difficult to ⚖️ it out .
In RESONATE trial >grade 3 afib in 3% of pts.
Most events occur within 3 mts of starting #ibrutinib
As we can see most ADRs are d/t off target kinase inhibition.
RESONATE trial : 44% bleeding events, most were minor.
However in the real world setting upto 19% had > grade 3 bleeds.
Concurrent use of anticoag and antiplat agents ⬆️⬆️ risk of major bleeds
Obviously CHA2 DS2 VASc is to be used and anticoag only if score >2.
Off label enoxaparin ✅
Best is to try alternate Rx , W/H #ibrutinib if possible.
Most worrisome ,Aspergillus Fumigatus IFI.
PcP another cause of concern
RESONATE reported a 24% incidence of >grade 3 infections.
⬇️ Activation of macrophages d/t BTK inhibition l/t ⬆️ A.fumigatus
But it's fortunately short lived and not very severe.
Another ADR d/t EGFR ⛔ is palpable pruritic rash ,this again is self limited.
Topical steroids help.
Indefinite therapy is a major issue.
Financial toxicity also needs to be addressed especially in 🇮🇳 where the majority are uninsured.