TY - JOUR
T1 - CML-384 Immunological Response to SARS-CoV-2 After Infection and/or Vaccination Among Chronic Myeloid Leukemia Patients – A Prospective Study
AU - Galvis, Marisol Miranda
AU - Bradshaw, Danielle
AU - Farmaha, Jaspreet
AU - Jones, Kimya
AU - Singh, Harmanpreet
AU - Vashisht, Ashutosh
AU - Sahajpal, Nikhil
AU - Kolhe, Ravindra
AU - Cortes, Jorge
N1 - Funding Information:
will be helpful in evaluating the pharmacodynamics of the drug. Objective: To assess the effect of fatty meals on nilotinib drug levels and correlate its in-vivo activity with STAT1, STAT5, and AKT1 levels. Design/Setting/Patients/Intervention: This single-center, open-label, pharmacokinetic /pharmacodynamic study included 30 patients with newly diagnosed CML–chronic phase. There were 5 cohorts with 6 patients enrolled in each. The dose of nilotinib in each cohort was 150 mg OD, 200 mg OD, 150 mg BD, 200 mg BD, and 300 mg BD. The drug was given on an empty stomach for the initial 8 days and with fatty meals for the next 8 days. Fatty meals were defined as 2 slices of bread with 10 g butter. Blood (2 mL) was withdrawn at specified time points: 0, 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, and 24 hours on day 1 and 0 and 3 hours on day 8. Nilotinib drug levels were estimated by liquid chromatography mass spectrometry. For assessment of the downstream signaling pathway, blood samples were drawn on days 1 and 8 of drug intake without food and day 8 of drug intake with food, and levels were assessed by ELISA. Main Outcome Measures: To assess serum drug levels of nilotinib along with STAT5, STAT1, and AKT1 levels in fasting and post-meal status. Results: Nilotinib had a significant dose-dependent food interaction, and higher doses showed greater increases in AUC and Cmax. The protein expression of the native form of STAT1 increased in the group of drug intake with food. The increase might have resulted from inhibition of STAT1 phosphorylation by nilotinib. Acknowledgments: The study is funded by a research grant from ICMR, New Delhi. Keywords: CML, nilotinib, food interactions, pharmacokinetics, pharmacodynamics
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/10
Y1 - 2022/10
N2 - Context: Patients with hematologic malignancies have an increased risk of SARS-CoV-2 infection, severe COVID-19, and higher mortality rates. Objective: We investigated the immunological response to SARS-CoV-2 after infection and/or vaccination and explored the impact of treatment response on antibody levels. Design: We added a cohort of CML patients to the ongoing study SPARTA. We collected saliva and peripheral blood to measure levels of SARS-CoV-2 antigen and antibodies. Results: From 10-1-2021 to 3-31-2022, we prospectively enrolled 69 participants (32 with CML, 37 non-cancer) with similar sociodemographic characteristics. There was a significant difference in the frequency of previous SARS-CoV-2 infections, where the control group had a higher percentage of patients previously diagnosed with COVID-19 (18.8% vs. 84%). Nevertheless, there was no difference in the detection of SARS-CoV-2 at the time of enrollment (0% vs. 5.6%). SARS-CoV-2 antibodies, either IgG or neutralizing (nAB), were detected in most of the participants regardless of cancer status (IgG, 84.4% in the CML cohort and 91.7% in the non-cancer cohort; nAB, 84.4% vs. 88.9%). The two groups had comparable IgG (mean 160.8 vs. 157.5 Ru/mL) and nAB (mean 1,473 vs. 1,509 ng/ml) levels. Overall, IgG and nAB levels were significantly higher in subjects who received the last vaccine dose within 6 months compared to those who received it ≥6 months previously (IgG, CML, mean 177.7 vs. 113.2, control 190.5 vs. 134.4; nAB, CML 1,784 vs. 951.9, control 2,066 vs. 1,335). Both groups had comparable mean antibody levels according to the time since the last dose (IgG, ≤6 months, 177.7 vs. 190.5, ≥6 months, 113.2 vs. 134.4; nAB, ≤6 months, 1,784 vs. 2,066, ≥6 months 951.9 vs. 1,335). There was no difference in the detection and levels of antibodies according to therapy with TKIs (IgG, mean 158.8 vs. 185.2; nAB, 1,515 vs. 1,883) or achieving MMR (IgG, mean 152.4 vs. 177.5; nAB, 1,447 vs. 1,686). Conclusions: The immunological response to SARS-CoV-2 among CML patients is comparable to that in non-CML subjects. TKI therapy and the response to treatment did not impact the development of antibodies. Moreover, antibody levels decreased over time, with the most significant drop after 6 months since the last immunization dose.
AB - Context: Patients with hematologic malignancies have an increased risk of SARS-CoV-2 infection, severe COVID-19, and higher mortality rates. Objective: We investigated the immunological response to SARS-CoV-2 after infection and/or vaccination and explored the impact of treatment response on antibody levels. Design: We added a cohort of CML patients to the ongoing study SPARTA. We collected saliva and peripheral blood to measure levels of SARS-CoV-2 antigen and antibodies. Results: From 10-1-2021 to 3-31-2022, we prospectively enrolled 69 participants (32 with CML, 37 non-cancer) with similar sociodemographic characteristics. There was a significant difference in the frequency of previous SARS-CoV-2 infections, where the control group had a higher percentage of patients previously diagnosed with COVID-19 (18.8% vs. 84%). Nevertheless, there was no difference in the detection of SARS-CoV-2 at the time of enrollment (0% vs. 5.6%). SARS-CoV-2 antibodies, either IgG or neutralizing (nAB), were detected in most of the participants regardless of cancer status (IgG, 84.4% in the CML cohort and 91.7% in the non-cancer cohort; nAB, 84.4% vs. 88.9%). The two groups had comparable IgG (mean 160.8 vs. 157.5 Ru/mL) and nAB (mean 1,473 vs. 1,509 ng/ml) levels. Overall, IgG and nAB levels were significantly higher in subjects who received the last vaccine dose within 6 months compared to those who received it ≥6 months previously (IgG, CML, mean 177.7 vs. 113.2, control 190.5 vs. 134.4; nAB, CML 1,784 vs. 951.9, control 2,066 vs. 1,335). Both groups had comparable mean antibody levels according to the time since the last dose (IgG, ≤6 months, 177.7 vs. 190.5, ≥6 months, 113.2 vs. 134.4; nAB, ≤6 months, 1,784 vs. 2,066, ≥6 months 951.9 vs. 1,335). There was no difference in the detection and levels of antibodies according to therapy with TKIs (IgG, mean 158.8 vs. 185.2; nAB, 1,515 vs. 1,883) or achieving MMR (IgG, mean 152.4 vs. 177.5; nAB, 1,447 vs. 1,686). Conclusions: The immunological response to SARS-CoV-2 among CML patients is comparable to that in non-CML subjects. TKI therapy and the response to treatment did not impact the development of antibodies. Moreover, antibody levels decreased over time, with the most significant drop after 6 months since the last immunization dose.
KW - CML
KW - COVID-19
KW - IgG
KW - SARS-CoV-2
KW - chronic myeloid leukemia
KW - neutralizing antibodies
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U2 - 10.1016/S2152-2650(22)01378-7
DO - 10.1016/S2152-2650(22)01378-7
M3 - Article
C2 - 36163923
AN - SCOPUS:85138167942
SN - 2152-2650
VL - 22
SP - S294-S295
JO - Clinical Lymphoma
JF - Clinical Lymphoma
ER -
