Table 5. . Adverse effects of antibody drugs.
| Author (year) study design | Antibody | Adverse effects ≥ Grade III | Common adverse effects | Ref. |
|---|---|---|---|---|
| Hansson et al. (2015) Phase I | BI-505 | Headache (n = 4), pyrexia (n = 3), infusion-related reactions (n = 1), fluid overload (n = 1), T-wave inversion (n = 1) | Fatigue (47%), pyrexia (32%), headache (32%), nausea (29%), chills (24%) | [24] |
| Callander et al. (2009) Abstract | Bevacizumab | DVT (n = 3), SOB (n = 2), atrial fibrillation (n = 3) | Fatigue | [57] |
| Somlo et al. (2011) Phase II | Bevacizumab | Fatigue (16.6%), HTN (16.6%), neutropenia (16.6%), hyponatremia (16.6%) | Not reported | [45] |
| Bevacizumab ± thalidomide | Lymphopenia (16.6%), fatigue (16.6%), pulmonary HTN (16.6%) | |||
| White et al. (2013) Phase II | Bevacizumab + bortezomib | Thrombocytopenia (28%), neutropenia (18%) | Anemia, diarrhea, fatigue, URTI, neuralgia | [44] |
| Bortezomib + placebo | Thrombocytopenia (30%), diarrhea (10%) | Anemia, diarrhea, fatigue, URTI, neuralgia | ||
| Rasche (2015) Phase I | PAT-SM6 | Neutropenia (8.3%), back pain (8.3%), bile duct stone (8.3%) | Neutropenia (50), leukopenia (67) | [76] |
| Orlowski et al. (2015) Phase II | Siltuximab + bortezomib | Neutropenia (49%), thrombocytopenia (48%) | Infections (62%), sensory neuropathy (49%) | [36] |
| Bortezomib + placebo | Neutropenia (24%), thrombocytopenia (34%) | Infections (49%), sensory neuropathy (51%) | ||
| Agura et al. (2009) Phase Ib | Dacetuzumab | Herpes zoster, renal failure | Infusion reactions, Grade I/II, fatigue (47%), neutropenia (28%), thrombocytopenia (25%), diarrhea (22%), constipation (19%), headache (19%) | [21] |
| Hussein et al. (2010) Phase I | Dacetuzumab | Total Grade III AE = 30%, thrombocytopenia (7%), aseptic meningitis (5%), renal failure (5%) | Fatigue (57%), headache (43%), nausea (23%), anemia (21%). Elevated LFTs (41%), anorexia, back pain, constipation, diarrhea, ocular hyperemia (21%) | [22] |
| Bensinger et al. (2012) Phase I | Lucatumumab | Thrombocytopenia (4%), increased LFTs (4%), increased lipase (4%) | Infusion reactions, anemia (7%), hypercalcemia (7%), pyrexia (7%) | [23] |
| Martin et al. (2014) Phase I | Isatuximab (SAR650984) | Pneumonia, fever, hyperglycemia, hypophosphatemia | Pneumonia (9%), fever (3%), apnea (3%), fatigue (3%), hyperglycemia (3%) | [11] |
| Martin et al. (2014) Phase Ib | Isatuximab SAR650984 | No DLT reported, IAR (6%) | Fatigue (41.9%), nausea (38.7%), URTI (38.7%), diarrhea (35.5%) | [13] |
| Richter et al. (2016) Phase II | Isatuximab SAR650984 | Not reported | Nausea (33%), fatigue (30%), dyspnea (26%), infusion related (49%) | [12] |
| Voorhees et al. (2009) Phase II | Siltuximab | Thrombocytopenia, anemia, neutropenia, abnormal LFTs, fatigue | Diarrhea (29%), nausea (22%), constipation (20%), fatigue (43%), peripheral edema (29%) | [37] |
| Siltuximab + dexamethasone | ||||
| Suzuki et al. (2015) Phase I | Siltuximab | No DLT, lymphopenia (89%), neutropenia (44%) | Abnormal LFTs (44%), rash (44%), hyperlipidemia (44%) | [38] |
| Rossi et al. (2009) Phase I | Atacicept | Neuropathy, epiploic appendicitis. | Infections, bone pains | [43] |
| Iida et al. (2016) Phase I | Tabalumab | Febrile neutropenia, tumor lysis syndrome, Ileus | Thrombocytopenia (81.3%), lymphopenia (43.8%), increased alanine aminotransferase (43.8%) | [77] |
| Raje et al. (2017) Phase II | Tabalumab | Thrombocytopenia (12 8%), pneumonia (9.1%) | Thrombocytopenia (37%), fatigue (37%), diarrhea (35%), constipation (32%) | [41] |
| Placebo | ||||
| Lesokhin et al. (2016) Phase Ib | Nivolumab | Pneumonitis (4%), myositis (4%), raised CPK (4%) | Seen in 52% patients | [47] |
| Badros et al. (2017) Phase II | Pembrolizumab | Hematologic (40%), hyperglycemia (25%), pneumonia (15%) | Pancytopenia (13%), hypothyroidism (10%) | [46] |
| Efebera et al. (2015) Phase I/II | Pidilizumab | Anemia 25%, neutropenia 23%, thrombocytopenia 34% | Fatigue (50%), anorexia (17%), hypophosphatemia (17%) | [48] |
| Chanan-Khan et al. (2010) Phase I | Lorvotuzumab mertansine | Peripheral neuropathy, fatigue, acute renal failure | Fatigue, peripheral neuropathy, headache, raised AST | [50] |
| Berdeja (2012) Phase I | Lorvotuzumab mertansine | Peripheral neuropathy, neutropenia (n = 1), hyperuricemia tumor lysis syndrome (n = 2) | Peripheral neuropathy (42%) | [49] |
| Heffner et al. (2012) Phase I/IIa | Indatuximab ravtansine (ADC) | Palmar-planter erythrodysesthesia syndrome (n = 1), elevated LFTs | Fatigue, anemia, diarrhea | [53] |
| Kelly et al. (2014) Phase I/IIa | Indatuximab ravtansine (ADC) | Mucosal inflammation (n = 1), anemia (n = 1) | Fatigue, hypokalemia, diarrhea | [52] |
| Kelly et al. (2016) Phase I/IIa | Indatuximab ravtansine (ADC) | Not reported | Diarrhea, fatigue, nausea | [51] |
| Benson et al. (2015) Phase I | IPH 2101 | Leucopenia (n = 1), neutropenia (n = 1) | Myelodysplasia (n = 1), neutropenia, IRR | [20] |
| Benson et al. (2012) Phase I | IPH 2101 | Not reported | Fatigue (n = 10), chills (n = 5), pyrexia (n = 5) | [19] |
| Kaufman et al. (2013) Phase I | Milatuzumab | Anemia 20%, CRS 4%, hypokalemia 4%, epistaxis 4% | Nausea (48%), fever (36%), CRS (20%), headache (20%), HTN (20%) | [16] |
| Lacy et al. (2008) Phase I | Figitumumab (CP 751, 871) | Anemia (2.1%), hyperglycemia (2.1%) | Anemia (6.4%), increased AST (6.4%) | [18] |
| Moreau et al. (2011) Phase I | AVE1642 | Hypercalcemia (n = 1), renal vein thrombosis (n = 1) | Not reported | [17] |
| San-Miguel et al. (2014) Phase II | VMP + placebo | All = 81%, neutropenia (43%), thrombocytopenia (25%), pneumonia (17%), median PFS = 17 months | Infections (17%), GI disorders (11%) | [39] |
| Siltuximab + VMP | All = 92%, neutropenia (62%), thrombocytopenia (44%), pneumonia (17%), median PFS = 17 months | Infections (29%), GI disorders (11.5%) | ||
| Shah et al. (2016) Phase I/II | Siltuximab | Pneumonia, thrombocytopenia | Fatigue (63.6%), constipation (54.5%), paresthesia (45.5%), myalgia (56.4%) | [40] |
| Baz et al. (2007) Phase II | Rituximab + MP | Diarrhea (31%), neutropenia (51%), anemia (47%), thrombocytopenia (40%) | Fever, fatigue, cough, dyspnea, diarrhea, nausea, diarrhea and constipation. Possible AE related to rituximab were IRR (11%) | [75] |
ADC: Antibody drug conjugate; AE: Adverse event; CRS: Cytokine release syndrome; DLT: Dose-limiting toxicity; DVT: Deep venous thrombosis; GI: Gastrointestinal; HTN: Hypertension; IAR: Infusion-associated reaction; IRR: Infusion-related reaction; LFT: Liver function test; m: Month; MP: Melphalan, prednisone; PFS: Progression-free survival; SOB: Shortness of breath; URTI: Upper respiratory tract infection; VMP: Bortezomib, melphalan and prednisone.