Biologics - heme

Question 1

All-trans retinoic acid/Arsenic

ATRA

Answer 1

Target: Retinoic acid receptor
USE: PML
TOXICITY:Capillary leak syndrome – vasoactive cytokine release → capillary leak→edema, fever, rash, hypotension
Inerstitial edema and infiltration of lungs, lymph nodes, spleen, liver, pericardium with maturing myeloid cells

Question 2

Imatinib

Dasatinib*

Answer 2

TARGET: Tyrosine Kinase Inhibitor – 
BCR-ABL
c-KIT
USE: CML, GI stromal tumors
TOXICITY:Edema
Rash
*not as susceptible to resistance
Metabolized by CYP3A4 – avoid grapefruit

Question 3

Trastuzumab

Answer 3

TARGET: Tyrosine Kinase Inhibitor –
HER2
MECHANISM:Binds extracellular HER-2/neu domain. Blocks ligand binding→ down regulate receptor
USE: breats + gastric cancer
TOXICITY:Cardiomyopathy →must monitor patient

“Trans2zumab”

Question 4

Cetuximab

pantiumumab

Answer 4

TARGET: EGFR-R inhibitor (extracellular)
USE: Stage IV colorectal cancer (wildtype KRAS)
Head and Neck cancer
TOXICITY: Rash (and acneiform eruption), elevated LFTs, diarrhea,
Hypersensitivity rxn on infusion, HYPOmagnesemia

Question 5

Erlotinib

Answer 5

TARGET: Inhibits tyrosine kinase domain of EGFR
USE: NSCLC
TOXICITY: Rash (acneiform eruption- note that rash indicates medication is working)
Metabolized by CYP3A4 – avoid grapefruit

Question 6

Crizotinib

Answer 6

TARGET: ALK inhibitor
USE: NSCLC (EML4-ALK1 translocation)
Must be wild type for EGFR and RAS

Question 7

Vemurafenib

Dabrafenib

Answer 7

TARGET: inhibits V600E BRAF mutation
USE: Malignant Melanoma
(BRAF +)
TOXICITY: Causes other skin cancers (cutaneous squamous cell and keratoacanthomas)
Oral and highly selective
Coadministered with trametinib (MEK inhibitor) to prevent skin cancers

Question 8

Lenalidomide

Answer 8

TARGET: Inhibits production of TNF-alpha and IL-10
USE: Multiple Myeloma
TOXICITY: Teratogen

Question 9

Bortezomib

carfilzomib

Answer 9

TARGET: proteasome inhibitor
MECHANISM: 26S proteasome inhibition→down regulation of NF-kB →G2-M phase arrest and apoptosis
USE: Multiple myeloma (1st line)
Mantle cell lymphoma
TOXICITY: Peripheral Nerve Damage – painful sensory neuropathy in stocking glove distribution; burning dysesthesias of fingers and toes
Herpes zoster reactivation
Myelosuppression

Question 10

Bevacizumab

Answer 10

TARGET: ANti-VEGF
MECHANISM: Binds VEGF-A and prevents it from binding VEGF-R. Prevents angiogenesis
USE: Colorectal cancer
Renal cell carcinoma
Wet macular degeneration
TOXICITY: HTN, LV dysfunction, wound healing complications
↑ risk of thromboembolic events, GI perforation

“BeVacizumab → Blood Vessel”

Question 11

Nivolumab

Pembrolizumab*

Answer 11

TARGET: PD-1 Inhibitor
MECHANISM: Bind PD-1 on T cells. Blocks binding to PD-L1 on tumor cells which would normally suppress cytotoxic activity of T-Cells
USE: NHL, Melanoma, NSCLC*
TOXICITY: Immune mediated pneumonitis, colitis, hepatitis, and endocrineopahties

Rash, musculoskeletal pain, pruritis

Question 12

Atezolizumab
Durvalumab
Avelumab

Answer 12

TARGET: PDL-1 Inhibitor
MECHANISM: Binds PDL-1 on tumor cells to restore T cell function
USE: uroepithelial carcinoma
TOXICITY: Immune mediated pneumonitis, colitis, hepatitis, and endocrineopahties

Rash, musculoskeletal pain, pruritis

Question 13

Ritixumab

Ofatumuma*

Answer 13

TARGET: Anti-CD20 antibody
MECHANISM: Binds CD20 on normal and neoplastic B cells. Results in complement mediated lysis, cellular toxicity + apoptosis induction
USE: NHL, CLL, DLBCL, ITP, Follicular lymphoma, Rheumatoid arthritis
TOXICITY: Anemia, neutropenia

Question 14

Alemtuzumab

Answer 14

TARGET: CD52 on normal and malignant B and T cells
MECHANSIM: deplete cell population leading to lymphopenia
USE: CLL

Question 15

Ipilimumab

Answer 15

TARGET: CTLA-4 on T-cells
MECHANISM: Prevent CD80/86 (on tumor cells) from delivering suppressive signals to T cells
USE: malignant melanoma, colorectal cancer

Question 16

Eculizumab

Answer 16

TARGET: C5 inhibitor
MECHANISM: prevent complement activation
USE: Paraoxysmal nocturnal hemoglobinuria