Table 2.
Immune (modulation) targeted therapy
| Class/drug | Target(s)/indication(s) | Common adverse effects/warnings |
|---|---|---|
| Angiogenesis inhibitors | Class effects: HTN, proteinuria, bleeding/hemorrhage, impaired wound healing, embryo-fetal toxicity | |
| Bevacizumab (Avastin®)[86] | VEGF; mCRC, nonsquamous NSCLC with carboplatin/paclitaxel, recurrent ovarian cancer, metastatic renal cell cancer, cervical cancer, recurrent glioblastoma | Epistaxis, headache, HTN, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation dis-order, back pain, exfoliative dermatitis Warnings: Perforation or fistula; arterial thromboembolic events; HTN; venous thromboembolic events; PRES; proteinuria, infusion reactions, embryo-fetal toxicity, ovarian failure |
| Bevacizumab-awwb (Mvasi®)[87] Avastin® Biosimilar not interchangeable with avastin (bevacizumab) | VEGF; mCRC, nonsquamous NSCLC with carboplatin/paclitaxel, recurrent ovarian cancer, metastatic renal cell cancer, cervical cancer, recurrent glioblastoma | Epistaxis, headache, HTN, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage, lacrimation disorder, back pain, exfoliative dermatitis Warnings: Perforation or fistula; arterial thromboembolic events; HTN; venous thromboembolic events; PRES; proteinuria, infusion reactions, embryo-fetal toxicity, ovarian failure |
| Ramucirumab (Cyramza®)[88] | VEGFR-2; advanced gastric/GEJ cancer, metastatic NSCLC, mCRC | HTN, diarrhea; when combined with chemotherapy, neutropenia, fatigue, stomatitis/mucosal inflammation, decreased appetite Warnings: ATEs, HTN, infusion-related reactions, impaired wound healing, clinical deterioration in patients with cirrhosis, RPLS, proteinuria, thyroid dysfunction, embryo-fetal risk |
| Autologous cellular vaccine | ||
| Sipuleucel-T (Provenge®)[85] | Prostate cancer antigen; prostate cancer, asymptomatic or minimally symptomatic metastatic, castration-resistant. Drug is combined prostate cancer antigen (PAP) plus GM-CSF plus patient's dendritic cells, used to stimulate an immune response against the tumor antigen | Chills, fatigue, fever, back pain, nausea, joint ache, headache Warnings: Drug is intended only for autologous use; acute infusion reaction; combination of vaccine plus chemotherapy and immunosuppressive drugs has not been studied; vaccine is not routinely tested for transmissible infectious diseases |
| Bispecific CD19-directed CD3 T-cell engager | ||
| Blinatumomab (Blincyto®)[79] | Target is CD19 protein on lymphocytes. CD-19-CD3 bi-specific as binds together cytotoxic T-cells and tumor cell antigen; PH-relapsed/refractory B-cell precursor ALL (adults and children) | Infections, pyrexia, headache, infusion-related reactions, anemia, febrile neutropenia, thrombocytopenia, neutropenia Warnings: Infections, reduced ability to drive and use machines, pancreatitis, preparation and administration errors, risk of serious adverse reactions in children if alcohol containing diluent is used; cytokine release syndrome may be life-threatening, neurological toxicities |
| CD20 (protein on B-lymphocte) directed MAb | Infections, infusion reactions, embryo-fetal toxicity, HSRs TLS | |
| Ibritumomab tiuxetan (Zevalin®)[89] | CD20; low-grade or follicular NHL | Cytopenias, fatigue, nasopharyngitis, nausea, abdominal pain, asthenia, cough, diarrhea, pyrexia Warnings: Serious infusion reactions, prolonged and severe cytopenias, severe cutaneous and mucocutaneous reactions, altered biodistribution, development of leukemia and MDS, extravasation, do not administer live viral vaccines, embryo-fetal toxicity |
| Obinutuzumab (Gazyvz®)[90] | CD20; follicular lymphoma, CLL | Infusion reactions, neutropenia, thrombocytopenia, diarrhea, cough, constipation, pyrexia, URI, UTI, arthralgia, sinusitis, asthenia, headache, herpesvirus infection, pneumonia, decreased appetite, alopecia, pruritus Warnings: Hepatitis B virus reactivation, PML, infusion reactions, HSRs, TLS, infections, neutropenia, thrombocytopenia, do not administer live viral vaccines before or during therapy |
| Ofatumumab (Arzerra®)[91] | CD20; CLL | Infusion reactions, neutropenia, febrile neutropenia, URIs, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, rash, nausea, URI Warnings: Hepatitis B virus reactivation, PML, infusion reactions, TLS, cytopenias |
| Rituximab (Rituxan®)[92] IV only | CD20+low grade or follicular NHL, CLL, rheumatoid arthritis, Wegener's granulomatosis and microscopic polyangiitis | Infusion reactions, fever, lymphopenia, chills, infection, asthenia, neutropenia, URI, nasopharyngitis, UTI, bronchitis, nausea, diarrhea, headache, muscle spasms, anemia, peripheral edema Warnings: Infusion reactions that are fatal, severe mucocutaneous reactions which may be fatal, hepatitis B reactivation, PML, TLS, infections, cardiac arrhythmias and angina, bowel obstruction and perforation, cytopenias, do not administer live virus vaccines before or during therapy |
| Rituximab and hyaluronidase human (Rituxan® Hycela)[93] SQ only | CD20+follicular NHL, diffuse large cell lymphoma, CLL | Infections, neutropenia, nausea, constipation, cough, fatigue, alopecia, anemia, thrombocytopenia, pyrexia, vomiting, injection site erythema Warnings: Severe mucocutaneous reactions which may be fatal, hepatitis B reactivation, PML, HSRs, TLS, infections, cardiac adverse events, renal toxicity, bowel obstruction and perforation, do not administer live virus vaccines before or during therapy, embryo-fetal toxicity |
| CD22 (protein on B-lymphocte) directed MAb | ||
| Inotuzumab ozogamicin (Besponsa™)[94] | CD22; relapsed/refractory B-cell ALL | Thrombocytopenia, neutropenia, infection, anemia, leukopenia, fatigue, hemorrhage, pyrexia, nausea, headache, febrile neutropenia, increased hepatic transaminase laboratory values, abdominal pain, hyperbilirubinemia Warnings: Hepatotoxicity, higher post-HCST nonrelapse mortality rate, myelosuppression, infusion-related reactions, QT interval prolongation, embryo-fetal toxicity |
| CD30 (protein on B-lymphocte) directed MAb | ||
| Brentuximab vedotin (Adcetris®)[95] | CD30; Hodgkin's lymphoma (consolidation after auto-HSCT or high risk of relapse); systemic or cutaneous anaplastic large cell lymphoma | Peripheral sensory neuropathy, fatigue, nausea, diarrhea, neutropenia, URI, pyrexia Warnings: JC virus infection resulting in PML, peripheral neuropathy, anaphylaxis and infusion reactions, hematologic toxicities, serious infections and opportunistic infections, TLS, hepatotoxicity, pulmonary toxicity, serious dermatologic reactions, GI complications, embryo-fetal toxicity |
| CD33 (protein on B-lymphocyte) directed MAb | ||
| Gemtuzumab ozogamicin (Mylotarg™)[96] | CD33; newly diagnosed CD33-positive AML adults, or treatment of relapsed CD33+AML in adults and children | Hemorrhage, infection, fever, nausea, vomiting, constipation, headache, increased AST/ALT laboratory tests, rash, mucositis Warnings: Hepatotoxicity, infusion-related reactions, hemorrhage (severe and potentially fatal), embryo-fetal toxicity |
| CD38 (protein on B-lymphocte) directed MAb | ||
| Daratumumab (Darzalex®)[97] | CD38; multiple myeloma | Infusion reactions, neutropenia, thrombocytopenia, fatigue, nausea, diarrhea, constipation, vomiting, muscle spasms, arthralgia, back pain, pyrexia, chills, dizziness, insomnia, cough, dyspnea, peripheral edema, peripheral sensory neuropathy, URI Warnings: Infusion reactions, interference with red blood cell cross-matching and antibody screening, neutropenia, thrombocytopenia |
| CD52 (protein on B-lymphocte) directed MAb | ||
| Alemtuzumab (Campath®)[98] | CD52 protein on B-cell CLL cells | Cytopenias, prolonged lymphopenia with increased risk for infection, infusion reactions, CMV infection and other infections, nausea, vomiting, diarrhea, insomnia. Embryo-fetal toxicity Warnings: Hematologic toxicity which may be fatal, infusion reactions, infections including opportunistic infections. Patient should receive prophylaxis for PCP while receiving the drug. Do not administer live vaccines while receiving or who have recently received the drug |
| EGFR inhibitors includes HER1 (EGFR1) and HER2 (EGFR2) | Dermatologic toxicity, infusion reactions, magnesium wasting (hypomagnesemia), diarrhea, embryo-fetal toxicity | |
| Ado-trastuzumab emtansine (Kadcyla®)[99] | HER2 (EGFR2); metastatic HER2+breast cancer | Fatigue, nausea, musculoskeletal pain, hemorrhage, thrombocytopenia, headache, increased hepatic transaminase values, constipation, epistaxis Warnings: Do not substitute drug for trastuzumab, hepatotoxicity with liver failure and death, reduced LVEF, embryo-fetal toxicity |
| Cetuximab (Erbitux®)[100] | EGFR1; mCRC (wild type), HNSCC | Cutaneous reaction (rash, pruritus, nail changes), headache, diarrhea, infection Warnings: Infusion reactions which may be fatal, cardiopulmonary arrest/sudden death occurred in 2%-3% of study patients with HNSCC also receiving RT |
| Necitumumab (Portrazza®)[101] | EGFR1; squamous NSCLC, with gemcitabine and cisplatin | Rash, hypomagnesemia Warnings: Cardiopulmonary arrest/sudden death (likely related to hypo-magnesemia), hypomagnesemia, VTE, ATE, dermatologic toxicities, infusion-related reactions, increased toxicity and mortality if given to a patient with nonsquamous NSCLC, embryo-fetal toxicity |
| Panitumumab (Vectibix®)[102] | EGFR1; mCRC (wild-type RAS gene) | Skin rash, paronychia, fatigue, nausea, diarrhea. In combination with FOLFOX chemotherapy, also stomatitis, mucosal inflammation, asthenia, anorexia, hypomagnesemia, hypokalemia, acneiform dermatitis, pruritus, dry skin Warnings: Dermatologic toxicities occurred in 90% of study patients, severe in 13% receiving monotherapy; increased progression/mortality or lack of benefit in patents with mutant RAS gene; electrolyte depletion; pulmonary fibrosis/ILD; ocular toxicities; embryo-fetal toxicity |
| Pertuzumab (Perjeta®)[103] | HER2 (EGFR2); HER2+breast cancer (neoadjuvant, metastatic) | In combination with other drugs: Diarrhea, alopecia, neutropenia, nausea, fatigue, rash, peripheral neuropathy, vomiting, thrombocytopenia, anemia Warnings: LVEF decrease, embryo-fetal toxicity, infusion-related reactions, HSRs including anaphylaxis |
| Trastuzumab (Herceptin®)[104] | HER2; HER-2 overexpressing adjuvant or metastatic breast cancer, metastatic gastric or GEJ adenocarcinoma | Headache, diarrhea, nausea, chills, fever, CHF, infection, insomnia, cough, rash, weight loss, URI, fatigue, thrombocytopenia, nasopharyngitis, dysgeusia, anemia, mucosal inflammation Warnings: Cardiomyopathy, infusion reactions, embryo-fetal toxicity, pulmonary toxicity, exacerbation of chemotherapy-induced neutropenia |
| Trastuzumab-dkst (Ogivri®)[105] Herceptin® Biosimilar not interchangeable with herceptin (trastuzumab) | HER2; HER-2 overexpressing adjuvant or metastatic breast cancer or metastatic gastric or gastroesophageal adenocarcinoma | Headache, diarrhea, nausea, chills, fever, CHF, infection, insomnia, cough, rash, weight loss, URI, fatigue, thrombocytopenia, nasopharyngitis, dysgeusia, anemia, mucosal inflammation Warnings: Cardiomyopathy, infusion reactions, embryo-fetal toxicity, pulmonary toxicity, exacerbation of chemotherapy-induced neutropenia |
| Immune checkpoint inhibitors | Immune-related toxicities, embryo-fetal toxicity | |
| Atezolizumab (Tecentriq®)[106] | PD-L1; locally advanced/metastatic urothelial cancer, metastatic NSCLC | Fatigue, decreased appetite, nausea, constipation, UTI, diarrhea, pyrexia, musculoskeletal pain Warnings: Immune-related: Hepatitis, colitis, pneumonitis, endocrinopathies, neurologic syndromes (e.g., myasthenic syndrome); ocular inflammatory toxicity; infection; infusion reaction; embryo-fetal toxicity |
| Avelumab (Bavencio®)[107] | PD-L1; advanced/metastatic urothelial cancer; metastatic Merkel cell carcinoma | Fatigue, musculoskeletal pain, diarrhea, nausea, infusion-related reaction, rash, decreased appetite, peripheral edema, UTI Warnings: Immune-mediated: Pneumonitis, hepatitis, colitis, endocrinopathies, nephritis, and renal dysfunction; infusion-related reactions, embryo-fetal toxicity |
| Durvalumab (Imfinzi™)[108] | PD-L1; locally advanced or metastatic urothelial cancer | Fatigue, musculoskeletal pain, constipation, decreased appetite, nausea, peripheral edema, UTI Warnings: Immune-mediated: Pneumonitis, hepatitis, colitis, endocrinopathies, nephritis; infection, infusion-related reactions, embryo-fetal toxicity |
| Ipilimumab (Yervoy®)[109] | CTLA4; adjuvant melanoma, metastatic melanoma | Fatigue, diarrhea, pruritus, rash, colitis; adjuvant dose: In addition to above, nausea, vomiting, headache, weight loss, pyrexia, decreased appetite, insomnia Warnings: Immune-mediated adverse events (hepatitis, endocrinopathies, colitis); embryo-fetal toxicity |
| Nivolumab (Opdivo®)[110] | Programmed death receptor-1; metastatic: NSCLC, melanoma alone or in combination with ipilimumab, renal cell cancer, HNSCC, urothelial cancer, CRC with dMMT/MSH-1, HCC, classical Hodgkins lymphoma | Fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia, cough, dyspnea, constipation, decreased appetite, back pain, arthralgia, URI, pyrexia; with ipilimumab: Fatigue, rash, diarrhea, nausea, pyrexia, vomiting, dyspnea Warnings: Immune-mediated: Pneumonitis, colitis, hepatitis, endocrinopathies, nephritis and renal dysfunction, skin adverse reaction, encephalitis; infusion reactions; complications of allogeneic HSCT after nivolumab; embryo-fetal toxicity |
| Pembrolizumab (Keytruda®)[111] | PD-1; unresectable or metastatic melanoma; metastatic NSCLC, HNSCC, urothelial cancer, solid tumors with dMMT/MSH-1, gastric cancer; classical Hodgkin's lymphoma | Fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation Warnings: Immune-mediated: Pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, skin adverse reactions, other immune-related toxicities; infusion-related reactions; complications of allogeneic HSCT after pembrolizumab; embryo-fetal toxicity |
| IECT | ||
| Axicabtagene ciloleucel (Yescarta®)[112] | Chimeric antigen receptor T-cell therapy; CD19 directed genetically modified autologous T-cell immunotherapy producing superior immune fighting cells against patient tumor; refractory or relapsed large B-cell lymphoma in adults | CRS, fever, hypotension, encephalopathy, tachycardia, fatigue, headache, decreased appetite, chills, diarrhea, febrile neutropenia, infections, hypoxia, tremor, cough, vomiting, dizziness, constipation, cardiac arrhythmias Warnings: CRS, which may be fatal, neurologic toxicities, which may be fatal, HSRs, serious infections, prolonged cytopenias, hypogammaglobulinemia, secondary malignancies, impairment of ability to drive or operate machinery during and for 8 weeks after drug treatment. Drug is available only through a restricted Yescarta REMS program |
| Tisagenlecleucel (Kymriah®)[113] | Chimeric antigen receptor T-cell therapy; CD19 directed genetically modified autologous T-cell immunotherapy producing superior immune fighting cells against patient tumor; refractory B-cell precursor ALL | CRS, hypogammaglobulinemia, infections, pyrexia, decreased appetite, headache, encephalopathy, hypotension, bleeding episodes, tachycardia, nausea, diarrhea, vomiting, viral infection, hypoxia, fatigue, acute kidney injury, delirium Warnings: CRS that may be fatal, neurological toxicities which may be severe, HSRs, prolonged cytopenias, serious infections, hypogammaglobulinemia, secondary malignancies, impairment of ability to drive or operate machinery during and for 8 weeks after drug treatment. Drug is available only through a restricted Kymriah REMS program |
| iMIDs | Class effects: Embryo-fetal toxicity | |
| Lenalidomide (Revlimid®)[114] | Anti-angiogenic mechanisms, T-cell costimulatory functions, stimulation of NK cells and T-cells; MM with dexamethasone; transfusion dependent anemia due to MDS due to deletion of 5q; relapsed MCL, maintenance therapy in MM after ASCT | Diarrhea, fatigue, anemia, constipation, neutropenia, peripheral edema, insomnia, muscle cramp/spasm, abdominal and back pain, nausea, asthenia, pyrexia, URI, nasopharyngitis, gastroenteritis, cough, rash, dyspnea, dizziness, decreased appetite, thrombocytopenia, tremor, pruritus, arthralgia, epistaxis, anemia Warnings: Embryo-fetal toxicity (causes birth defects or embryo-fetal death), hematologic toxicity, VTE, ATE, increased mortality if drug is used for CLL (not an indication), hepatotoxicity, cutaneous reactions, TLS, tumor flare reactions, impaired stem cell mobilization, early mortality in MCL. Only available through Revlimid REMS program |
| Pomalidomide (Pomalyst®)[115] | Anti-angiogenic mechanisms, T-cell costimulatory functions, stimulation of NK cells and T-cells; relapsed MM together with dexamethasone | Fatigue, asthenia, neutropenia, anemia, constipation, nausea, diarrhea, dyspnea, URI, back pain, pyrexia Warnings: Embryo-fetal toxicity (causes birth defects or embryo-fetal death), hematologic toxicity, VTE, ATE, hepatotoxicity, HSRs, TLS. Only available through Pomalyst REMS program |
| Thalidomide (Thalomid®)[116] | Anti-angiogenic mechanisms, T-cell costimulatory functions, stimulation of NK cells and T-cells; newly diagnosed MM, with dexamethasone, other conditions | Fatigue, hypocalcemia, edema, constipation, neuropathy (sensory and motor), dyspnea, muscle weakness, neutropenia, rash/desquamation, confusion, anorexia, nausea, anxiety/agitation, asthenia, tremor, fever, weight loss, thrombosis/embolism, weight gain, dizziness, dry skin, somnolence Warnings: Embryo-fetal toxicity (causes birth defects or embryo-fetal death), hematologic toxicity, VTE, ischemic heart disease, drowsiness and somnolence, peripheral neuropathy, dizziness and orthostatic hypotension, neutropenia, thrombocytopenia, increased HIV viral load, bradycardia, Stevens-Johnson syndrome, seizures, TLS, HSRs. Only available through Thalomid REMS program |
| Oncolytic viral therapy | ||
| Talimogene laherparepved (T-vec®, Imlygic®)[83] | Genetically modified oncolytic viral therapy. Patient's tumor cells, when injected into tumor locally, destroys tumor cells so antigens can be fragmented and mounted on dendritic APC's which then can activate T-cells to kill the tumor antigen-containing cells elsewhere in the body; stimulates local and systemic immune responses. Local treatment of unresectable, cutaneous, subcutaneous, and nodal melanoma lesions that have recurred after initial surgery | Fatigue, chills, pyrexia, nausea, influenza-like illness, injection site pain Warnings: Accidental exposure to drug may cause transmission of drug and herpetic infection; herpetic infection; injection site complications; immune-mediated events; plasmacytoma at injection site; objective airway disorder requiring careful injection of lesions near major airways |
| PDGF-α | ||
| Olaratumumab (Lartruvo®)[81] | Platelet-derived growth factor receptor alpha; soft tissue sarcoma, in combination with doxorubicin | Nausea, fatigue, musculoskeletal pain, mucositis, alopecia, vomiting, diarrhea, decreased appetite, abdominal pain, neuropathy, headache Warnings: Infusion-related reactions, embryo-fetal toxicity |
HTN: Hypertension, VEGF: Vascular endothelial growth factor, mCRC: Metastatic colorectal cancer, NSCLC: Nonsmall cell lung cancer, PRES: Posterior reversible encephalopathy syndrome, VEGFR: VEGF receptor, GEJ: Gastroesophageal junction, ATEs: Arterial thromboembolic events, RPLS: Reversible posterior leukoencephalopathy syndrome, PAP: Prostatic acid phosphatase, GM-CSF: Granulocyte-macrophage-colony stimulating factor, PH: Philadelphia-chromosome negative, ALL: Acute lymphoblastic leukemia, NHL: Non-Hodgkin's lymphoma, MDS: Myelodysplastic syndrome, CLL: Chronic myelogenous leukemia, URIs: Upper respiratory infections, UTI: Urinary tract infection, PML: Progressive multifocal leukoencephalopathy, HSRs: Hypersensitivity reactions, TLS: Tumor lysis syndrome, GI: Gastrointestinal, AML: Acute myeloid leukemia, AST: Aspartate aminotransferase, CD: Cluster of differentiation, identifying specific proteins on B-cell lymphocytes, e.g., CD20, ALT: Alanine aminotransferase, CMV: Cytomegalovirus, PCP: Pneumocystis jiroveci (formerly carinii) pneumonia, LVEF: Left ventricular ejection fraction, HNSCC: Head and neck squamous cell cancer, VTE: Venous thromboembolic event, CHF: Congestive heart failure, PD-L1: Programmed death ligand-1, CTLA4: Cytotoxic T-lymphocyte antigen 4, HCC: Hepatocellular carcinoma, IECT: Immune effector cell therapy, CRS: Cytokine release syndrome, REMS: Risk evaluation and mitigation strategy, iMIDs: Immunomodulatory drugs, MM: Multiple myeloma, NK: Natural killer cell: Type of lymphocyte that can kill invading virus or cancer cells without using antigen detection (uses enzymatic granules to kill the other cell) and is part of the innate immune system, MCL: Mantle cell lymphoma, 5q: Short arm of chromosome 5, ASCT: Autologous stem cell transplant, APCs: Antigen presenting cell, such as dendritic cells, PDGFR: Platelet-derived growth factor receptor, SLAMF-7: Signaling lymphocytic activation molecule family member 7 protein on multiple myeloma and NK cells, leading to death of myeloma cells by NK cells, PD-1: Programmed death receptor-1, dMMR: Mismatch repair (gene) deficient, MSI-1: microsatellite instability-high, HER2: Human epidermal growth factor receptor, HSCT: Hematopoietic stem cell transplant, RT: Radiation therapy, MSH-1: mismatch repair protein