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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Hum+Vaccin+Immunother
2016 ; 12
(11
): 2777-2789
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Pembrolizumab (Keytruda)
#MMPMID27398650
Kwok G
; Yau TC
; Chiu JW
; Tse E
; Kwong YL
Hum Vaccin Immunother
2016[Nov]; 12
(11
): 2777-2789
PMID27398650
show ga
The programmed cell death protein 1 (PD1) is one of the checkpoints that
regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2
results in transduction of negative signals to T-cells. PD1 expression is an
important mechanism contributing to the exhausted effector T-cell phenotype. The
expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor
cells to evade anti-tumor immunity. Blockade of PD1 is an important
immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized
monoclonal anti-PD1 antibody that has been extensively investigated in numerous
malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced
overall response rates (ORRs) of 21-34%. It was superior to another immune
checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma.
In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of
19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the
treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a
valid response predictor. Molecular analysis also showed that tumors with high
gene mutation burdens, which might result in the formation of more tumor-related
neo-antigens, had better responses to pembrolizumab. In malignancies including
lymphomas and other solid tumors, preliminary data showed that ORRs of around
20-50 % could be achieved. Adverse events occurred in up to 60% of patients, but
grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse
events including thyroid dysfunction, hepatitis and pneumonitis are more serious
and may lead to cessation of treatment.
|Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
[MESH]
|Antineoplastic Agents/adverse effects/*therapeutic use
[MESH]
|Drug-Related Side Effects and Adverse Reactions/epidemiology
[MESH]
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