BACKGROUND: Treatment with monoclonal antibodies (mAbs) against programmed cell death protein 1 receptor is subject to high variation in treatment outcome among cancer patients. For these agents, no exposure-response (ER) relationships have been investigated in routine health care settings. However, ER relationships have been identified for several other mAbs used in oncology. Methods to conveniently measure serum concentrations of anti-programmed cell death protein 1 mAbs in routine health care may clarify possible ER relationships. Therefore, the authors aimed to develop an enzyme-linked immune sorbent assay (ELISA) for the measurement of both nivolumab and pembrolizumab serum concentrations of treated cancer patients. METHODS: Optimal capture antigen and detection antibody concentrations were selected based on titrations. Nivolumab calibration standards ranging from 0.2 to 300 ng/mL were tested in duplicate. Accuracy was assessed in 2 recovery experiments. Intra- and interassay variations were assessed on 3 different days by 2 independent technicians. The developed ELISA was also set up for pembrolizumab calibration curves. Cross-reactivity of nivolumab measurements with ipilimumab was assessed. Of one nivolumab treated patient, serum concentrations in follow up samples were measured and presented. RESULTS: Nivolumab calibration standards of 0.20-25 ng/mL were used. Nivolumab trough concentrations after 1 cycle in 8 patients ranged from 17.3 to 31.1 mcg/mL. The range of accuracy was 84%-105%, whereas intra- and interassay variations showed a coefficient of variation of 5.5% and 10.1%, respectively. No cross-reactivity with ipilimumab was detected. Pembrolizumab trough concentrations (n = 8) ranged from 9.1 to 19.7 mcg/mL after 1 infusion. CONCLUSIONS: The in-house-developed ELISA provides the opportunity to measure both nivolumab and pembrolizumab serum concentrations. This may help identify possible ER relationships in treated cancer patients and may potentially lead to dose adjustments in the future.
BACKGROUND: Treatment with monoclonal antibodies (mAbs) against programmed cell death protein 1 receptor is subject to high variation in treatment outcome among cancerpatients. For these agents, no exposure-response (ER) relationships have been investigated in routine health care settings. However, ER relationships have been identified for several other mAbs used in oncology. Methods to conveniently measure serum concentrations of anti-programmed cell death protein 1 mAbs in routine health care may clarify possible ER relationships. Therefore, the authors aimed to develop an enzyme-linked immune sorbent assay (ELISA) for the measurement of both nivolumab and pembrolizumab serum concentrations of treated cancerpatients. METHODS: Optimal capture antigen and detection antibody concentrations were selected based on titrations. Nivolumab calibration standards ranging from 0.2 to 300 ng/mL were tested in duplicate. Accuracy was assessed in 2 recovery experiments. Intra- and interassay variations were assessed on 3 different days by 2 independent technicians. The developed ELISA was also set up for pembrolizumab calibration curves. Cross-reactivity of nivolumab measurements with ipilimumab was assessed. Of one nivolumab treated patient, serum concentrations in follow up samples were measured and presented. RESULTS:Nivolumab calibration standards of 0.20-25 ng/mL were used. Nivolumab trough concentrations after 1 cycle in 8 patients ranged from 17.3 to 31.1 mcg/mL. The range of accuracy was 84%-105%, whereas intra- and interassay variations showed a coefficient of variation of 5.5% and 10.1%, respectively. No cross-reactivity with ipilimumab was detected. Pembrolizumab trough concentrations (n = 8) ranged from 9.1 to 19.7 mcg/mL after 1 infusion. CONCLUSIONS: The in-house-developed ELISA provides the opportunity to measure both nivolumab and pembrolizumab serum concentrations. This may help identify possible ER relationships in treated cancerpatients and may potentially lead to dose adjustments in the future.
Authors: M Sureda; E Calvo; J J Mata; V Escudero-Ortiz; E Martinez-Navarro; A Catalán; J Rebollo Journal: Clin Transl Oncol Date: 2021-02-13 Impact factor: 3.405
Authors: Daan P Hurkmans; Sebastiaan D T Sassen; Karlijn de Joode; Lisanne Putter; Edwin A Basak; Annemarie J M Wijkhuijs; Markus Joerger; Reno Debets; Birgit C P Koch; Cor H Van der Leest; Marco W J Schreurs; Astrid A M van der Veldt; Joachim G J V Aerts; Ron H J Mathijssen; Stijn L W Koolen Journal: J Immunother Cancer Date: 2021-06 Impact factor: 13.751
Authors: Daan P Hurkmans; Edwin A Basak; Tanja van Dijk; Darlene Mercieca; Marco W J Schreurs; Annemarie J M Wijkhuijs; Sander Bins; Esther Oomen-de Hoop; Reno Debets; Markus Joerger; Arlette Odink; Astrid A M van der Veldt; Cor H van der Leest; Joachim G J V Aerts; Ron H J Mathijssen; Stijn L W Koolen Journal: J Immunother Cancer Date: 2019-07-19 Impact factor: 13.751
Authors: Alyssa Marie M Castillo; Trang T Vu; Sophia G Liva; Min Chen; Zhiliang Xie; Justin Thomas; Bryan Remaily; Yizhen Guo; Uma L Subrayan; Travis Costa; Timothy H Helms; Donald J Irby; Kyeongmin Kim; Dwight H Owen; Samuel K Kulp; Thomas A Mace; Mitch A Phelps; Christopher C Coss Journal: JCSM Rapid Commun Date: 2021-02-09