Journal of Oncology / 2019 / Article / Tab 3

Review Article

Immune Checkpoint Inhibition in Classical Hodgkin Lymphoma: From Early Achievements towards New Perspectives

Table 3

Adverse Events linked to immune checkpoint inhibitors in cHL.

AgentReference / PhaseNo. of patientsMost Common AEGrade 3 or 4 AEsComments

NivolumabAnsell et al. (Checkmate 039) [7]2378 Drug-related adverse events of any grade; the most common (>10):
(i) Rash (22%)
(ii) Thrombocytopenia (17%)
(iii) Pyrexia (13%)
(iv) Fatigue (13%)
(v) Diarrhea (13%)
(vi) Nausea (13%)
(vii) Pruritus (13%)
22 Drug-related adverse events of grade 3:
(i) Myelodysplastic syndrome
(ii) Pancreatitis
(iii) Pneumonitis
(iv) Stomatitis
(v) Colitis
(vi) Gastrointestinal inflammation
(vii) Thrombocytopenia
(viii) Increased lipase levels
(ix) Decrease lymphocyte level
(x) Leukopenia
(i) Two patients discontinued treatment because of drug toxicity.
(ii) AE reversible in all the patients except the 2 who discontinued.
Younes and al. (Checkmate 205) [8]8089 Drug-related adverse events of any grade; the most common (>10):
(i) Fatigue (25%)
(ii) IRR (20%)
(iii) Rash (15%)
(iv) Arthralgie (14%)
(v) Pyrexia (14%)
(vi) Nausea (13%)
(vii) Diarrhea (10%)
(viii) Pruritus (10%)
21 Drug related grade 3:
(i) Neutropenia (5%)
(ii) Increased lipase levels (3%)
(iii) Increased ALT (3%)
(iv) Increased AST (3%)
(v) Abdominal pain (3%)
(vi) Dyspnea (1%)
(vii) Pneumonia (1%)
(viii) Hepatitis (1%)
(ix) Rash (1%)
(x) Arthritis (1%)
(xi) Syncope (1%)
4 Drug-related AE grade 4:
(i) Increased lipase (3%)
(ii) Decreased neutrophil count (1%)
AE leading to discontinuation:
(i) Treatment related autoimmune hepatitis (1 patient)
(ii) Treatment related increased ALT and ASAT concentrations (1 patient)
(iii) Death from multi-organ failure (1 patient) not treatment-related.
Armand et al. (Checkmate 205) [57]243Drug-related AE any grade:
(i) Fatigue (23%)
(ii) Diarrhea (15%)
(iii) Infusion-related reaction (14%)
(iv) Rash (12%)
(v) Pruritus (10%)
(vi) Nausea (10%)
Immune-mediated AE:
(i) Hypothyroidism /thyroiditis (12%)
(ii) Rash (9%)
(iii) Hepatitis (5%)
(iv) Pneumonitis (4%)
(v) Hyperthyroidism (2%)
(vi) Diabetes mellitus <1%
Drug-related AE grade 3-4:
(i) Lipase increased (5%)
(ii) Neutropenia (3%)
(iii) ALT increased (3%)
(iv) AST increased (2%)
7% discontinue treatment because of drug-related AE:
(i) Pneumonitis (2%)
(ii) Autoimmune hepatitis (1%)
Maruyama and al. [60]17Most common adverse events
(i) Pyrexia (41.2%)
(ii) Pruritus (35.3%)
(iii) Rash (35.3%)
(iv) Hypothyroidism (29.4%)
23.5 grade 3 or 4 AEs:
(i) Anemia
(ii) Lymphopenia
(iii) Thrombocytopenia
(iv) Pyrexia
(v) Hepatic function abnormal
(vi) Pneumonia
(vii) Hyponatremia
(viii) Fulminant type 1 diabetes mellitus
(ix) Interstitial lung disease
(x) Rash
6 serious AE in 3 patients (all judged drug-related):
(i) Pyrexia
(ii) Hepatic function abnormal
(iii) Hyponatremia
(iv) Fulminant type 1 diabetes mellitus∗
(v) Interstitial lung disease∗
(vi) Rash
∗ Led to treatment discontinuation

PembrolizumabArmand et al. (Keynote 013) [61]3168 Drug-related AE
(i) Hypothyroidism (16%)
(ii) Nausea (13%)
(iii) Diarrhea (16%)
(iv) Pneumonitis (10%)
16 Drug-related grade 3 AEs:
(i) Colitis
(ii) Increased ALT and AST levels
(iii) Nephrotic syndrome
(iv) Joint swelling
(v) Back pain
(vi) Axillary pain
(i) Two patients discontinued due to grade 2 pneumonitis and grade 3 nephrotic syndrome
Chen and al. (Keynote 087) [62]210TRAE grade 1 or 2:
(i) Hypothyroidism (11.9%)
(ii) Pyrexia (10%)
(iii) Fatigue (8.6%)
(iv) Rash (7.6%)
(v) Diarrhea (6.2%)
6.4 TRAE grade 3/4:
(i) Neutropenia (2.4%)
(ii) Dyspnea (1%)
(iii) Diarrhea (1%)
(iv) Pyrexia (0.5%)
(v) Cough (0.5%)
(vi) Fatigue (0.5%)
(vii) Hypothroidism (0.5%)
(i) 4.3% discontinued because of TRAEs
(ii) 12.4% experienced TRAEs resulting in treatment interruptions.
Zinzani et al. Keynote 087 updated results (ASH 2018) [63]21072.9 TRAE of any grade:
(i) Hypothyroidism (14.3%)
(ii) Pyrexia (11.4%)
(iii) Fatigue (11%)
(iv) Rash (11%)
11.9 TRAE grade 3/4:
(i) Neutropenia (2.4%)
(ii) Diarrhea (1.4%)
6.7% of patients discontinued treatment due to TRAE

AvelumabChen et al. [91]31Treatment-related AE of any grade:
(i) IRR (26.7%)
(ii) Nausea (20%)
(iii) Rash (20%)
(iv) Fatigue (13.3%)
36.7 grade ≥3 AEs – details NA2 patients (6.7%) discontinued treatment due to IRR

SintilimabShi et al. (ORIENT-1) [68]9693 treatment-related AE of any grade:
(i) Pyrexia 41%
(ii) Hypothyroidism 20%
(iii) Increased ALT 14%
(iv) Pneumonitis 11%
(v) Infusion reaction 9%
(vi) Rash 11%
(vii) Increase AST 8%
(viii) Decreased platelet counts 10%
54 immune-related AE
18 treatment-related AE grade 3 or 4
11 Drug-related serious adverse events:
(i) Pneumonitis 3%
(ii) Lung infection 3%
(iii) Infusion reaction 2%
(iv) Upper respiratory tract infection 1%
(v) Liver function abnormality 1%
(vi) Decreased platelet counts 1%
(vii) Peripheral neuropathy 1%
(viii) Hyperthyroidism 1%
3% (3 patients) discontinued treatment due to adverse events
(i) 1 patient with grade 2 pneumonitis
(ii) 1 patient with grade 4 liver function abnormality
(iii) 1 patient with grade 3 pneumonitis and grade 4 decreased platelet count.

IRR = infusion related reactions; AE = adverse event; TRAE = treatment-related AE; NA = not available.

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