Acute Promyelocytic Leukemia

 All-trans retinoic acid/Arsenic

o Major toxicity: “capillary leak syndrome” AKA Differentiation syndrome can be
caused by both ATRA and arsenic. Occurs in about 25% of patients treated with
ATRA. The etiology of the differentiation syndrome is incompletely understood,
but is thought to be due to release of inflammatory vasoactive cytokines, causing
capillary leak, fever, edema, rash, and hypotension. Patients demonstrate
interstitial edema and infiltration of the lung, lymph nodes, spleen, liver, and
pericardium with maturing myeloid cells.

Tyrosine kinase inhibitors

 Metabolized in the liver by CYP3A4. Patients should avoid grapefruit. Toxicity includes
edema and skin rash.
 Imatinib targets BCR-ABL TK but also c-KIT; constitutive activation of c-kit is associated
with gastrointestinal stromal tumors (GIST). Imatinib is used for adjuvant therapy here

HER2
 Trastuzumab- recombinant DNA-derived humanized monoclonal antibody that binds to
the extracellular domain of HER-2/neu. It blocks the ligand from binding and
downregulates the receptor. Approved for HER-2./neu positive breast cancer or GI.
Adverse events: Patients must be monitored for CARDIOMYOPATHY

EGF-R inhibitors
 Acneiform eruption is the prototypical cutaneous adverse reaction associated with all
EGFR inhibitors occurring in 80% pf patients. Several studies have noted an association
between rash and increased overall response rate or survival, suggesting that the skin
eruption may be a surrogate marker for efficacy of EGFR inhibitor therapy. Patients
develop erythematous papules or pustules in areas rich in sebaceous glands, such as
the scalp, face, and particularly the nose, cheeks, nasolabial folds, and perioral region.
 Cetuximab-chimeric mab against extracellular EGR-R; may have immunologic effects
as well. Only recommended for patients with wild-type RAS. Adverse events: skin rash;
hypersensitivity reaction on infusion; HYPOmagnesemia; increased LFTs
 Erlotinib- inhibits tyrosine kinase domain of EGF-R. Also, metabolized in the liver by
CYP3A4. Patients should avoid grapefruit and drugs such as warfarin.

ALK inhibitor
 Crizotinib

BRAF inhibitor
 Vemurafenib- oral and highly selective inhibitor of BRAF (effective for the BRAFV600E
mutation). Currently approved for treatment of BRAF mut positive malignant melanoma.

Immune modulatory drugs

 TERATOGEN; inhibit TNF-alpha; IL-10 production
 Lenalidomide

Proteosome inhibitors
 Bortezomib- widely used first line therapy for multiple myeloma.
 o Exerts its main cytotoxic effects through inhibition of the 26S proteasome.
Resulting in down regulation of NF-kB signaling pathway which is activated in
these patients. Adverse event: Peripheral nerve damage is one of the most
significant nonhematologic toxicities of bortezomib occurring in 60-75% of
patients treated with twice weekly dosing. The predominant feature is a painful
sensory neuropathy in a stocking glove distribution with burning dysesthesias of
the fingers and toes.

Anti-VEGF
 Bevacizumab -(anti-VEGF) binds to and prevents VEGF-A from binding to the VEGF
receptor. Adverse events: HTN; increased incidence of arterial thromboembolic events
(e.g. TIA, stroke, angina), LV dysfunction; wound healing complications and GI
perforation.

Immune Checkpoint inhibitors

PD-1 inhibitors
 Nivolumab -binds to PD-1 on T cells blocking the binding to PD-L1 on tumor cells which
would normally suppress the cytotoxic activity of the T cells.
 Atezolizumab -bind to PDL-1 on tumor cells to restore T cell function

AntiCD20 antibody
 Rituximab- chimeric murine-human monoclonal IgG1 that binds to CD20 on normal and
neoplastic B cells. Causes complement mediated lysis; and cellular toxicity with
induction of apoptosis. Can cause anemia or neutropenia. Indicated for: CLL; DLBCL;
follicular lymphoma