Held: Oral Anticancer Agents in Hematology – 1

What drugs are classified as immunomodulatory (IMID) agents, and how are they generally thought to have antineoplastic effects?

How do the elimination processes of the IMID agents differ, and what characteristic common to myeloma patients may tend to not favor lenolidamide?

Lenalidomide	Renal elimination Dose reduce for CrCL <60 mL/min
Pomalidomide	Hepatic elimination
Thalidomide	Hydrolysis (non-renal, non-hepatic)

Which IMID would be least favored in a patient with T2DM and peripheral neuropathy?

Thalidomide- highest risk of neuropathies

What is the class REMS/ETASU for the IMID drugs, and why is it in place?

• To prevent risk embryo-fetal exposure to imids

• To inform prescribers, pts and pahramcists on the serious risks and saafe use conditions

Limited day supply ??

What prophylaxis is recommended for patients receiving IMID therapy?

Thromboprophylaxis → Aspirin 325 daily due to risk of VTE, MI and stroke

Which drugs are classified as BTK inhibitors?

• Ibrutinib

• Acalbrutinib

• Zanubrutinib

• Pirtobrutinib

All have BRUT

Against what type of cell line are BTK inhbitors used?

B lymphocytes

Which of the BTK inhibitors will most likely need a reduction of dose for moderate to severe renal impairment?

Pirtobrutinib

Which of the BTK inhibitors will most likely be affected by other drugs that induce or inhibit CYP3A4?

ALL! Ibrutinib, Acalbrutinib, Zanubrutinib, Pirtobrutinib

What is the most common adverse effect affecting the GI system among the BTK inhibitors?

Diarrhea

Which drugs are classified as PI3K inhibitors, and how are they generally thought to have antineoplastic effects?

Idelalisib

Duvelisib

Apelisib

Which drug is an inhibitor of BCL2? How does inhibiting BCL-2 lead to cell death?

• Venetoclax

Leads to cell death by increases proteins like BIM that increase BAX and BAK that leads to cytochrome C release from mitochondria, triggering apoptosis

Should venetoclax be dose-adjusted in a patient with renal impairment?

No, it is hepatically metabolized

Should venetoclax be dose-adjusted in a patient receiving posaconazole?

Yes, any concomitant azole antifungal

What changes in blood chemistries are expected from Tumor Lysis Syndrome (TLS), and what are the cardiac and renal implications of these changes?A

IDKKKKKKKKKK SHE DIDNT TALK ABOUT THIS ! someone help!

What other pretreatment (besides possibly hydroxyurea) is routinely employed in patients who will receive venetoclax?

Allopurinol
Rasburicase (high risk)

hydration

What serious adverse effects can be expected from treatment with idelalisib? How would you monitor for them?