Therapy Toxicities

Grant Whitebloom

Immune Checkpoint Inhibitor Toxicities

  • Immune checkpoint inhibitors (ICIs) augment the endogenous immune response against tumors, which may lead to autoimmune-like toxicities, known as immune-related adverse events (irAEs).
  • CTCAE Grading: Grade 1 – Mild; Grade 2 – Moderate; Grade 3 – Severe; Grade 4 – Life threatening or disabling; Grade 5 – Death related to irAE.
  • Treatment: low-dose glucocorticoids (prednisone, 0.5 mg/kg) for mild adverse events, high dose glucocorticoids (prednisone, 1-2 mg/kg) for severe adverse events. Depending on the irAE severity, future ICI therapy may be permanently discontinued.
Adverse Event Type Incidence with anti-CTLA-4 (e.g. ipilimumab) Incidence with anti-PD1/PD-L1 (e.g. nivolumab, pembrolizumab)
Cutaneous (rash, pruritus, TEN) 40% 40%
Colitis 25% 5%
Hypothyroidism 5-10% 10-20%
Hepatotoxicity 3-9% 2-5%
Hypophysitis 10% rare
Pneumonitis 2-5% 2-5%
Myocarditis 1% 1%
Neurotoxicity (GBS, myasthenia gravis, encephalitis) 4% 6%

Cytotoxic Agent Toxicities

Class Agent Side Effect
Alkylating agents busulfan pulmonary fibrosis or diffuse alveolar hemorrhage
cyclophosphamide myopericarditis, hemorrhagic cystitis (prevention: hydration; monitoring: daily UA, tx: mesna)
ifosfamide encephalopathy (tx: methylene blue), nephrotoxicity, hemorrhagic cystitis
Antimetabolites 5-Fluorouracil (5-FU) / Capecitabine (metabolized to FU) myelosuppression, coronary vasospasm, palmar-plantar erythrodysesthesia, mucositis
cladribine, pentostatin dose reduced for CrCl
cytarabine (Ara-C) irreversible cerebellar ataxia (if high dose, neuro checks required), conjunctivitis (prevent with prophylactic steroid eye drops)
gemcitabine transient transaminitis, peripheral edema, rash; rarely: pulmonary toxicity, hemolytic uremic syndrome, capillary leak syndrome, PRES
methotrexate stomatitis, hepatotoxicity, renal failure, high dose requires leucovorin
Antitumor antibiotics anthracyclines (doxorubicin, daunorubicin, idarubicin) HFrEF (need TTE prior). Most notable with doxorubicin.
bleomycin Pulmonary fibrosis. Potentiated with G-CSF
Monoclonal antibodies alemtuzumab severe and prolonged cytopenias
bevacizumab HTN, proteinuria, hyperglycemia, hypomag, arterial thromboembolism, pulm hemorrhage, GI bleeding/fistulas/perforation, wound healing complications, HFrEF
rituximab hypophos, hepatotoxicity, HBV reactivation (screen all pts), peripheral neuropathy; transfusion reaction during 1st-time infusion
Platinum agents cisplatin, oxaliplatin, carboplatin nephrotoxicity (worst with cisplatin), renal tubular acidosis, neurotoxicity (paresthesia, cold sensitivity, cramps, peripheral neuropathy), ototoxicity (high frequency hearing loss), constipation, hypomag
Taxanes docetaxel, paclitaxel hypersensitivity reaction (often require premedication with steroids and H1/H2 blockers), peripheral neuropathy
Topoisomerase inhibitors irinotecan, topotecan, etoposide irinotecan: acute diarrhea can be treated with atropine; delayed with Imodium/Lomotil
Tyrosine kinase inhibitors imatinib, dasatinib, nilotinib, bosutinib QTc prolongation, pulmonary effusion, hepatotoxicity
Vinca alkaloid vincristine peripheral neuropathy and ototoxicity (vestibular system lost first)

Other treatments and toxicities

Agent

Adverse event(s)

Management
Belzutifan Anemia and hypoxia Stop belzutifan, transfuse, supplement O2
BiTE/BiAb/ CAR T Cells Cytokine release syndrome, ICANS See CAR T Cell Section
Radiation Therapy See Radiation Toxicity section (ie Skin, HEENT, GI) See Radiation Toxicity section
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