Mechanisms/Indications
This small molecule inhibitor is used n R/R AML with FLT3 mutation positive disease and is a more potent inhibitor of FLT3
What is Gilteritinib
The non-GVHD/MF small molecule inhibitor that has a warning for pancreatitis and should be interrupted until resolution.
What is gilteritinib
Bonus: what dose should we resume at?
Dose reduction for fedratinib if CrCl between 15-29
What is 200mg daily
Should belumosudil be taken with food, without food, or irregardless of food.
What is with food
What is the starting dose for ruxolitinib for chronic GVHD if being given with fluconazole 200 mg daily
Bonus: What about acute gVHD?
This small molecule inhibitor is utilized in IDH2 positive R/R AML disease
What is Enasidenib
This side effect is associated with rapid proliferation of myeloid cells with symptoms such as fever, effusions, hypotension, edema. And typically resolves with steroid therapy and/or dose interruption.
What is differentiation syndrome?
Bonus: what is the typical dose/schedule of steroids we give for treatment?
Dose adjustment for belumosudil if given with PPI?
What is 200mg BID (twice the frequency)
Bonus: Why
Should olutasidenib be taken with food, without food, or irregardless of food
What is - without food
Dose that ivosidenib should be reduced to given concurrent therapy with strong CYP3A inhibitor
What is 250 mg daily
This small molecule inhibitor mimics endogenous BH3-only proteins which lead to rapid induction of apoptosis
What is venetoclax?
Bonus: Which is the specific receptor this inhibits?
Fedratinib is associated with _____ and patients on therapy should be monitored closely for mental status changes while on therapy
What is encephalopathy (including wernickes)
Bonus: What should we correct prior to starting therapy and if encephalopathy occurs administer high doses of?
Bonus knowledge: DOI: 10.1124/dmd.114.058883
Fedratinib inhibits carrier mediated uptake of thiamine, as seen by caco-2-cells (a type of colon cell) in this study
Dose adjustments are typically not required for this side effect of enasidenib due to how it alters the metabolism of said side effect. No patients dose reduced in the clinical trial for this side effect.
What is hyperbilirubinemia
Bonus: What is the gene that enasidenib interferes with that contributes to this?
This FLT3 inhibitor has moderate-high (>30%) emetogenic potential and necessitates pre-dose antiemetics
What is midostaurin
Bonus: what is the recommended NCCN anti-emesis therapy? What additional interaction may this cause with midostaurin?
If patient recently discontinued a strong CYP3A4 inhibitor while on fedratinib 200 mg daily, what dose should we adjust to?
What is 300 mg daily.
Bonus ? : when to adjust to 400mg once daily
This small molecule inhibitor is indicated for intermediate or high risk primary or secondary myelofibrosis with a platelet count less than 50k
What is Pacritinib
This agent has significant warning for musculoskeletal ADRS and should have baseline CPK levels prior to initiation
What is Glasdegib?
Bonus: At what ULN of CPK should we interrupt Glasdegib?
Dose reduction for midostaurin if QTc between 470-500 per RATIFY protocol
What is 50 mg daily
Bonus : should we adjust back to 100 daily in same cycle if no other QTc causes can be found?
Bonus 2: when do we interrupt therapy for QTc?
Ruxolitinib should not be abruptly discontinued except for ______ when being used for aGVHD
What is thrombocytopenia
Is the max recommended steady daily dose after ramp up phase if patient was receiving voriconazole as antifungal therapy while on venetoclax for AML
What 100 mg daily
Bonus: what if posaconazole was the agent?
This small molecule inhibitor has indication for both acute and chronic GVHD and is typically 1st line therapy after steroid therapy or in steroid refractory.
What is ruxolitinib?
Bonus: What is the starting dose for acute GVHD ____ and what is the starting dose for chronic GVHD ______
What criteria would place patients at high risk for TLS in patients being treated with venetoclax for CLL/SLL
What is Lymph node > 10CM
OR
Absolute lymphocyte count (ALC) >25k and any LN >5 cm
Bonus: What prophylaxis may be indicated if baseline uric acid is elevated and patient is unable to tolerate aggressive hydration?
Patient is on Ruxolitinib 10mg BID for cGVHD, T. Bili increases to 8.0 x ULN. This is the recommended management for ruxolitinib.
What is - hold jakafi for 14 days until resolution, then resume at 1 dose level lower upon recovery.
Myelofibrosis agent that has specific recommendations to hold 1 week prior to any planned surgical or invasive procedures
What is Pacritinib
Should posaconazole be continued for patients starting 7 +3 and midostaurin (strong CYP3A4 induction therapy?
Options: switch to Micafungin, switch to Fluconazole, Continue
What is Continue
Rationale: Patients are at very high risk of invasive fungal infections during induction chemotherapy for AML, risk of midostaurin toxicities should be weighed against this but generally can continue triazoles (posaconazole and voriconazole) given close monitoring available