Altered splenic [89Zr]Zr-rituximab uptake in patients with interstitial lung disease not responding to rituximab: could this indicate a splenic immune-mediated mechanism? (2024)

Adams, H., Meek, B., van de Garde, E. M., van Moorsel, C. H., Vugts, D. J., Keijsers, R. G., & Grutters, J. C. (2020). Altered splenic [89Zr]Zr-rituximab uptake in patients with interstitial lung disease not responding to rituximab: could this indicate a splenic immune-mediated mechanism? American Journal of Nuclear Medicine and Molecular Imaging, 10(4), 168-177. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486548/

Adams, Human ; Meek, Bob ; van de Garde, Ewoudt Mw et al. / Altered splenic [89Zr]Zr-rituximab uptake in patients with interstitial lung disease not responding to rituximab : could this indicate a splenic immune-mediated mechanism?. In: American Journal of Nuclear Medicine and Molecular Imaging. 2020 ; Vol. 10, No. 4. pp. 168-177.

@article{219ce80c6f3748b695be1e0178247b92,

title = "Altered splenic [89Zr]Zr-rituximab uptake in patients with interstitial lung disease not responding to rituximab: could this indicate a splenic immune-mediated mechanism?",

abstract = "Rituximab (RTX) for immune-mediated inflammatory disease (IMID) with interstitial pneumonitis (IP) results in non-response in about a third of patients for reasons not well understood. Complete peripheral B-cell depletion in IMID-IP does not seem to correlate with successful treatment outcome. A hypothesis is that splenic B cells might play a role in B-cell recovery and attraction of na{\"i}ve B cells in non-responsive patients. The aim of this post hoc analysis of clinical trial data is to search for indicators in [89Zr]Zr-rituximab PET/CT data from the spleen that might explain non-responsiveness. PET/CT data of 20 patients with IMID-IP, who were enrolled in a phase II trial and treated with RTX were analyzed. Clinical outcome was categorized into responders (RSP) and non-responders (NR) after 6 months of initial RTX by two independent pulmonologists. Patients were examined separately to search for associations between clinical outcome, splenic activity on PET/CT, lymphocyte counts and other biomarkers. Treatment failure was found in 6/20 patients (30%) while all patients exhibited B-cell depletion from the circulation. NR patients demonstrated significantly higher splenic activity than RSP patients (non-preload protocol: SUV 4.9±1.96 and SUV 2.3±1.08 respectively, P=0.025). No correlations between treatment outcome and serum lymphocyte subsets were found. Our findings suggest a potential splenic mechanism in IMID-IP patients non-responding to RTX and warrant further consideration and investigation.",

keywords = "Spleen, clinical research, interstitial lung disease, rituximab, [89Zr]Zr-rituximab, PET/CT, CD20 cells, immunology",

author = "Human Adams and Bob Meek and {van de Garde}, {Ewoudt Mw} and {van Moorsel}, {Coline Hm} and Vugts, {Danielle J} and Keijsers, {Ruth G} and Grutters, {Jan C}",

note = "AJNMMI Copyright {\textcopyright} 2020.",

year = "2020",

month = aug,

day = "25",

language = "English",

volume = "10",

pages = "168--177",

journal = "American Journal of Nuclear Medicine and Molecular Imaging",

issn = "2160-8407",

publisher = "e-Century Publishing Corporation",

number = "4",

}

Adams, H, Meek, B, van de Garde, EM, van Moorsel, CH, Vugts, DJ, Keijsers, RG & Grutters, JC 2020, 'Altered splenic [89Zr]Zr-rituximab uptake in patients with interstitial lung disease not responding to rituximab: could this indicate a splenic immune-mediated mechanism?', American Journal of Nuclear Medicine and Molecular Imaging, vol. 10, no. 4, pp. 168-177. <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486548/>

Altered splenic [89Zr]Zr-rituximab uptake in patients with interstitial lung disease not responding to rituximab: could this indicate a splenic immune-mediated mechanism? / Adams, Human; Meek, Bob; van de Garde, Ewoudt Mw et al.
In: American Journal of Nuclear Medicine and Molecular Imaging, Vol. 10, No. 4, 25.08.2020, p. 168-177.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Altered splenic [89Zr]Zr-rituximab uptake in patients with interstitial lung disease not responding to rituximab

T2 - could this indicate a splenic immune-mediated mechanism?

AU - Adams, Human

AU - Meek, Bob

AU - van de Garde, Ewoudt Mw

AU - van Moorsel, Coline Hm

AU - Vugts, Danielle J

AU - Keijsers, Ruth G

AU - Grutters, Jan C

N1 - AJNMMI Copyright © 2020.

PY - 2020/8/25

Y1 - 2020/8/25

N2 - Rituximab (RTX) for immune-mediated inflammatory disease (IMID) with interstitial pneumonitis (IP) results in non-response in about a third of patients for reasons not well understood. Complete peripheral B-cell depletion in IMID-IP does not seem to correlate with successful treatment outcome. A hypothesis is that splenic B cells might play a role in B-cell recovery and attraction of naïve B cells in non-responsive patients. The aim of this post hoc analysis of clinical trial data is to search for indicators in [89Zr]Zr-rituximab PET/CT data from the spleen that might explain non-responsiveness. PET/CT data of 20 patients with IMID-IP, who were enrolled in a phase II trial and treated with RTX were analyzed. Clinical outcome was categorized into responders (RSP) and non-responders (NR) after 6 months of initial RTX by two independent pulmonologists. Patients were examined separately to search for associations between clinical outcome, splenic activity on PET/CT, lymphocyte counts and other biomarkers. Treatment failure was found in 6/20 patients (30%) while all patients exhibited B-cell depletion from the circulation. NR patients demonstrated significantly higher splenic activity than RSP patients (non-preload protocol: SUV 4.9±1.96 and SUV 2.3±1.08 respectively, P=0.025). No correlations between treatment outcome and serum lymphocyte subsets were found. Our findings suggest a potential splenic mechanism in IMID-IP patients non-responding to RTX and warrant further consideration and investigation.

AB - Rituximab (RTX) for immune-mediated inflammatory disease (IMID) with interstitial pneumonitis (IP) results in non-response in about a third of patients for reasons not well understood. Complete peripheral B-cell depletion in IMID-IP does not seem to correlate with successful treatment outcome. A hypothesis is that splenic B cells might play a role in B-cell recovery and attraction of naïve B cells in non-responsive patients. The aim of this post hoc analysis of clinical trial data is to search for indicators in [89Zr]Zr-rituximab PET/CT data from the spleen that might explain non-responsiveness. PET/CT data of 20 patients with IMID-IP, who were enrolled in a phase II trial and treated with RTX were analyzed. Clinical outcome was categorized into responders (RSP) and non-responders (NR) after 6 months of initial RTX by two independent pulmonologists. Patients were examined separately to search for associations between clinical outcome, splenic activity on PET/CT, lymphocyte counts and other biomarkers. Treatment failure was found in 6/20 patients (30%) while all patients exhibited B-cell depletion from the circulation. NR patients demonstrated significantly higher splenic activity than RSP patients (non-preload protocol: SUV 4.9±1.96 and SUV 2.3±1.08 respectively, P=0.025). No correlations between treatment outcome and serum lymphocyte subsets were found. Our findings suggest a potential splenic mechanism in IMID-IP patients non-responding to RTX and warrant further consideration and investigation.

KW - Spleen

KW - clinical research

KW - interstitial lung disease

KW - rituximab

KW - [89Zr]Zr-rituximab

KW - PET/CT

KW - CD20 cells

KW - immunology

UR - https://pubmed.ncbi.nlm.nih.gov/32929395/

M3 - Article

C2 - 32929395

SN - 2160-8407

VL - 10

SP - 168

EP - 177

JO - American Journal of Nuclear Medicine and Molecular Imaging

JF - American Journal of Nuclear Medicine and Molecular Imaging

IS - 4

ER -

Adams H, Meek B, van de Garde EM, van Moorsel CH, Vugts DJ, Keijsers RG et al. Altered splenic [89Zr]Zr-rituximab uptake in patients with interstitial lung disease not responding to rituximab: could this indicate a splenic immune-mediated mechanism? American Journal of Nuclear Medicine and Molecular Imaging. 2020 Aug 25;10(4):168-177.