Table 3.
Adverse effects of monoclonal Antibodies drugs.
| Author, Year, Study Design | Antibody | Adverse Effects ≥ Grade III | Common Adverse Effects |
|---|---|---|---|
| Hansson,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%) |
| Callander, 2009 | Bevacizumab | DVT (n = 3), SOB (n = 2), A fib (n = 3) | Fatigue |
| Somlo, 2011, Phase II | Bevacizumab | Fatigue (16.6%), HTN (16.6%), Neutropenia (16.6%), Hyponatremia (16.6%) | NR |
| Bevacizumab ± Thalidomide | Lymphopenia (16.6%), Fatigue (16.6%), Pulmonary HTN (16.6%) | ||
| White, 2013, Phase II | Bevacizumab + Bortezomib | Thrombocytopenia (28%), Neutropenia (18%) | Anemia, Diarrhea, Fatigue, URTI, Neuralgia |
| 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) |
| Orlowski, 2015, Phase II | Siltuximab + Bortezomib | Neutropenia (49%), Thrombocytopenia (48%) | Infections (62%), Sensory neuropathy (49%) |
| Bortezomib + Placebo | Neutropenia (24%), Thrombocytopenia (34%) | Infections (49%), Sensory neuropathy (51%) | |
| Agura, 2009, Phase 1b | Dacetuzumab | Herpes Zoster, Renal failure | Infusion reactions, grade (I/II), Fatigue (47%), Neutropenia (28%), Thrombocytopenia (25%), Diarrhea (22%), Constipation (19%), Headache (19%) |
| Husein, 2010, Phase I | Dacetuzumab | Total grade 3 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%) |
| Bensinger, 2012, Phase I | Lucatumumab | Thrombocytopenia (4%), Increased LFTs (4%), Increased Lipase (4%) | Infusion reactions, Anemia (7%), Hypercalcemia (7%), Pyrexia (7%) |
| Martin, 2014, Phase I | Isatuximab (SAR650984) | Pneumonia, Fever, Hyperglycemia, Hypophosphatemia, | Pneumonia 9%, fever (3%), apnea (3%), fatigue (3%), hyperglycemia (3%) |
| Richter, 2016, Phase II | Isatuximab SAR650984 | NR | Nausea (33%), Fatigue (30%), Dyspnea (26%), Infusion related 49% |
| Martin. Phase Ib, 2017 | Isatuximab + Len + Dex | pneumonia (9%), fatigue (7%). Hypokalemia, anaphylaxis, febrile neutropenia (5% each). | Thrombocytopenia (38%), anemia (25%), Neutropenia (60%), |
| Martin, 2014, Phase Ib | Isatuximab + Len + Dex | No DLT reported, IAR (6%) | Fatigue (41.9%), Nausea (38.7), URTI(38.7%), Diarrhea(35.5%) |
| Voorhesse, 2009, Phase II | Siltuximab | Thrombocytopenia, anemia, Neutropenia, abnormal LFTs, fatigue. | Diarrhea (29%), Nausea (22%), Constipation (20%), Fatigue (43%) Peripheral edema (29%) |
| Siltuximab + Dexamethasone | |||
| Suzuki, 2015, Phase I | Siltuximab | No DLT, Lymphopenia (89%), Neutropenia (44%) | Abnormal LFTs (44%), Rash (44%), Hyperlipidemia (44%) |
| Rossi,2009, Phase I | Atacicept | Neuropathy, Epiploic appendicitis. | Infections, Bone Pains |
| Shinsuke Iida, 2016, Phase I | Tabalumab | Febrile Neutropenia, Tumor lysis syndrome, Ileus. | Thrombocytopenia (81.3%), Lymphopenia (43.8%), Increased alanine aminotransferase (43.8%) |
| Reje, 2017, Phase II | Tabalumab | Thrombocytopenia (12 8%), Pneumonia (9.1%) | Thrombocytopenia (37%), Fatigue (37%), Diarrhea (35%), Constipation (32%) |
| Placebo | |||
| Lesokhin, 2016, Phase Ib | Nivolumab | Pneumonitis (4%), Myositis (4%), Raised CPK (4%) | seen in 52% patients |
| Badros, 2017, Phase II | Pembrolizumab | Hematologic (40%), Hyperglycemia (25%), pneumonia (15%) | Pancytopenia (13%), Hypothyroidism (10%) |
| Efebera, 2015, Phase I/II | Pidilizumab | Anemia 25%, neutropenia 23%, thrombocytopenia 34% | Fatigue (50%), anorexia (17%), hypophosphatemia (17%) |
| Channan, 2010, Phase I | Lorvotuzumab mertansine | Peripheral neuropathy, Fatigue, Acute renal failure | Fatigue, peripheral neuropathy, Headache, Raised AST |
| Berdeja, 2012, Phase I | Lorvotuzumab mertansine | Peripheral neuropathy, Neutropenia n = 1, Hyperuricemia Tumor lysis syndrome n = 2 |
Peripheral neuropathy (42%) |
| Heffner, 2012, Phase I/IIa | Indatuximab Ravtansine (ADC) | Palmar-planter eryhtrodysesthesia syndrome (N = 1), Elevated LFTs | Fatigue, Anemia, Diarrhea |
| Kelly, 2014, PhaseI/IIa | Indatuximab Ravtansine (ADC) | Mucosal inflammation (n = 1), Anemia (n = 1) | Fatigue, Hypokalemia, Diarrhea |
| Kelly, 2016, PhaseI/IIa | Indatuximab Ravtansine (ADC) | NR | Diarrhea, Fatigue, Nausea |
| Benson, 2015, phase I | IPH 2101 | leucopenia n = 1, neutropenia n = 1 | Myelodysplasia n = 1, neutropenia, IRR |
| Benson, 2012, Phase I | IPH 2101 | NR | Fatigue n = 10, Chills n = 5, pyrexia n = 5 |
| Kaufman,2013, Phase I | Milatuzumab | Anemia 20%, CRS 4%, Hypokalemia 4%, Epistaxis 4% | Nausea (48%), Fever (36%), CRS (20%), Headache (20%), HTN (20%) |
| Lacy, 2008, Phase I | Figitumumab (CP 751,871) | Anemia (2.1%), Hyperglycemia (2.1%) | Anemia (6.4%), Increased AST (6.4%) |
| Lacy, 2008, Phase I | Figitumumab (CP 751,871) | Muscle weakness (3.7%), Increased AST (3.7%) | Anemia (7.4%), Increased ALT (11%) |
| Moreau,2011, Phase I | AVE1642 | Grade III hyperglycemia n = 1 | NR |
| Moreau,2011, Phase I | AVE1642 | Hypercalcemia n = 1, renal vein thrombosis n = 1 | NR |
| Miguel, 2014, Phase II | VMP + Placebo | All = 81%, Neutropenia (43%), Thrombocytopenia (25%), Pneumonia (17%), Median PFS = 17m | Infections (17%), GI disorders (11%) |
| Miguel, 2014, Phase II | Siltuximab + VMP | All = 92%, Neutropenia (62%), Thrombocytopenia (44%), Pneumonia (17%), Median PFS = 17m | Infections (29%), GI disorders (11.5%) |
| Siltuximab | Pneumonia, Thrombocytopenia | Fatigue (63.6%), Constipation (54.5%), Paresthesia (45.5%), Myalgia (56.4%) | |
| Baz, 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%) |
| Vorhees, 2013, Phase II | Siltuximab | Thrombocytopenia 28%, Anemia 43%, Neutropenia 7% | Neutropenia 29%, Anemia 35%, Thrombocytopenia 49%, Fatigue 43%, Abnormal Hepatic Function 31%, Diarrhea 29%, Edema 29%, Dyspnea 27%, Dizziness 25%, Nausea 28%, Insomnia 28%, Weight increase 20% |
| Siltuximab + Dexa | Thrombocytopenia 26%, Anemia 16%, Neutropenia 18%, Fatigue 8% | NR | |
| Ribrag, 2017, Phase I | Pembrolizumab | Myalgia 3% | Asthenia 17%, Pruritus 3%, Arthralgia 3%, Fatigue 3%, Hyperglycemia 3%, Blurred vision 3%, Aspartate Aminotransferase increased 3% |
| Rasche, 2015, Phase I | PAT-SM6 | Neutropenia 8% | Neutropenia 50%, Leukopenia 66%, Increase in C reactive protein 8%, Hypertriglyceridemia 8% |
| Raje, 2016, Phase I | Tabalumab | Peripheral Sensory Neuropathy 15%, Fatigue 6%, Diarrhea 8%m Thrombocytopenia 31%m Anemia 6%, Neutropenia 15%, Pneumonia 13%, Hypokalemia 8%, Renal Failure 8%, Gi Hemorrhage 4%, Musculoskeletal pain 6% | Peripheral Sensory Neuropathy 63%, Fatigue 58%m Diarrhea 54%, Nausea 48%, Thrombocytopenia 33%, Anemia 23%, |
| Raab, 2016, Phase I/IIa | MOR 202 | NR | IRRs 10% |
| Patnaik, 2014, Phase I | Ficlatuzumab | Hyper/Hypokalemia, Diarrhea, Fatigue | Peripheral edema, fatigue, nausea |
| Orlowski, 2015, Phase II | Siltuximab + placebo | AE grade >3: 74%. Neutropenia 29%, Thrombocytopenia 34%, Bleeding events <2%, Infections 14% | Neutropenia 36%, Thrombocytopenia 45%, Peripheral Sensory Neuropathy 51%, Diarrhea 35%, Anemia 29%, Fatigue 27%, Infection 49% |
| Siltuximab + Bortezomib | AE grade >3: 91%. Neutropenia 49%, Thrombocytopenia 48%, Bleeding events <2%, infection 16% | Neutropenia 59%, Thrombocytopenia 57%, Peripheral Sensory Neuropathy 49%, Diarrhea 35 = 6%, Anemia 31%, Fatigue 27%, Infection 62% | |
| Mikhael, 2017, Phase IB | Isatuximab + Dexa Pomalidomide |
Neutropenia 92%, Thrombocytopenia 32% | Fatigue 62%, Diarrhea 35%, Dyspnea 31% |
| Martin, 2017, Phase IB | Isatuximab + Lenalidomide + Dexa | Anemia 25%, Lymphopenia 58%, Neutropenia 60%, Leukopenia 53%, Thrombocytopenia 38%, Fatigue 7%, Pneumonia 9%, Febrile Neutropenia 5%, Anaphylactic Reaction 5%, Hypokalemia 5% | Anemia 98%, Lymphopenia 95%, Neutropenia 89%, Leukopenia 91%, Thrombocytopenia 91%, IARs 56%, Diarrhea 53%, Fatigue 49%, URTI 40%, Nausea 35%, Insomnia 32%, Cough 26%, Headache 23%, Muscle spasm 23%, Vomiting 23% |
| Lida, 2016, Phase I | Tabalumab + Bortezomib + Dexa | >Grade3 AE: 81.3% | Thrombocytopenia 81%, Lymphopenia 43%, Anemia 31%, Increase Alanine Aminotransferase 43%, GI disturbances 62%, Constipation 38% |
| Lendvai, 2016, Phase Ib | Isatuximab + Dexa Lenalidomide | NR | IARs 65%, Fatigue 46%, Pyrexia 35%, Diarrhea 31% |
| Fouquet, 2018, Phase I | F50067 + Dexa Lenalidomide | Thrombocytopenia 64%, Neutropenia 57%, Anemia 14% | Thrombocytopenia 100%, Neutropenia 93%, Asthenia 7%, Hyperhidrosis 7%, Pyrexia 7%, Dyspnea 7%, Pulmonary Embolism 7%, Femoral Neck Fracture 7%, Rectal hemorrhage 7% |
| Brighton, 2017, Phase II | Siltuximab | NR | Infections and Infestations 38%, Renal and Urinary Disorders 7% |
| Placebo | NR | Infections and Infestations 33%, Renal and Urinary Disorders 16% | |
| Belch, 2011, Phase II | Bortezomib +/- Mapatumumab | Overall >Grade 3 AE. Arm A: 88.6%, Arm B10: 69.7%, Arm B20: 61% | Hematological, Peripheral Sensory Neuropathy |
| Badros, 2016 | Pembrolizumab + Pomalidomide + Dexa | Anemia 21%, Neutropenia 40%, Lymphopenia 15%, Thrombocytopenia 8%, Fatigue 15%, Hyperglycemia 25%, URI 25%, Rash 10% | Dyspnea 54%, Dizziness 44%, Increased Creatinine 38%, Edema 35%, Rash 30%, Interstitial Pneumonitis 13%, Hypothyroidism 10% |
| Ansell, 2016, Phase I | Nivolumab + Ipilimumab | NR | NR |
Abbreviations: ADC; Antibody drug conjugate, VMP; Bortezomib melphalan prednisone, MP; Melphalan prednisone, GI; Gastrointestinal, CRS: Complement release syndrome, IRR; Infusion related reactions, DLT; Dose limiting toxicity, PFS: Progression free survival, NR: not reported, Dexa; dexamethasone.