Correlation of Peripheral Chimeric Antigen Receptor T-cell (CAR-T Cell) mRNA Expression Levels with Toxicities and Outcomes in Patients with Diffuse Large B-cell LymphomaChristian Messerli1, Gertrud Wiedemann2, Naomi Porret2, Michael Nagler3, Katja Seipel4, Barbara Jeker1, Urban Novak1, Sacha Zeerleder2, Ulrike Bacher2, Thomas Pabst11University Hospital and University of Bern, Department of Medical Oncology, Bern, Switzerland
2University Hospital and University of Bern, Department of Hematology and Central Hematology Laboratory, Bern, Switzerland
3University Institute of Clinical Chemistry, University Hospital and University of Bern, Bern, Switzerland
4University of Bern, Department for Biomedical Research, Bern, Switzerland
Cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are significant complications in patients with relapsed/refractory diffuse large B-cell lymphoma undergoing chimeric antigen receptor T-cell (CAR-T cell) therapy. However, it remains unclear whether CAR-T cell expression itself is clinically relevant. We assessed CAR-T cell mRNA expression and DNA concentration by digital droplet PCR in peripheral blood from 14 sequential CAR-T cell recipients. Patients were grouped according to CAR-T cell peak expression. Patients with high CAR-T cell peak expression (8 patients; 57%) had higher rates of ICANS (p=0.0308) and intensive care unit admission (p=0.0404), longer durations of hospitalization (p=0.0077), and, although not statistically significant, a higher rate of CRS (p=0.0778). There was a correlation of CAR-T cell mRNA expression with DNA concentration, but CAR-T cell expression levels failed to correlate to response or survival. Our data suggest that higher CAR-T cell peak mRNA expression is associated with increased risk for ICANS and possibly CRS, requiring further investigation in larger studies. Keywords: Non-Hodgkin lymphoma, Lymphomas, Neoplasia, Transplant-related toxicity, Stem cell transplantation, Molecular biology
Diffüz Büyük B-hücreli Lenfomalı Hastalarda Periferik Kimerik Antijen Reseptör T-hücresi (CAR-T Hücresi) mRNA Ekspresyon Düzeylerinin Toksisiteler ve Sonuçlarla KorelasyonuChristian Messerli1, Gertrud Wiedemann2, Naomi Porret2, Michael Nagler3, Katja Seipel4, Barbara Jeker1, Urban Novak1, Sacha Zeerleder2, Ulrike Bacher2, Thomas Pabst11University Hospital and University of Bern, Department of Medical Oncology, Bern, Switzerland
2University Hospital and University of Bern, Department of Hematology and Central Hematology Laboratory, Bern, Switzerland
3University Institute of Clinical Chemistry, University Hospital and University of Bern, Bern, Switzerland
4University of Bern, Department for Biomedical Research, Bern, Switzerland
Sitokin salımı sendromu (CRS) ve immün efektör hücre ile ilişkili nörotoksisite sendromu (ICANS), kimerik antijen reseptörü T-hücresi (CAR-T hücresi) tedavisi gören nüksetmiş/refrakter diffüz büyük B-hücreli lenfoma hastalarında önemli komplikasyonlardır. Bununla birlikte, CAR-T hücre ifadesinin klinikle ilişkili olup olmadığı belirsizliğini korumaktadır. Ondört CAR-T hücre alıcısından periferik kanda dijital damlacık PCR’ı ile CAR-T hücresi mRNA ekspresyonunu ve DNA konsantrasyonunu değerlendirdik. Hastalar, CAR-T hücre pik ifadesine göre gruplandırıldı. Yüksek CAR-T hücre pik ekspresyonu olan hastalar (8 hasta; %57) daha yüksek ICANS (p=0,0308) ve yoğun bakıma yatış (p=0,0404), daha uzun hastanede yatış süreleri (p=0,0077) ve istatistiksel olarak anlamlı olmasa da, daha yüksek CRS oranına sahipti (p=0,0778). CAR-T hücresi mRNA ekspresyonu ile DNA konsantrasyonu arasında bir korelasyon vardı, ancak CAR-T hücresi ekspresyon seviyeleri, yanıt veya hayatta kalma ile korelasyon göstermedi. Verilerimiz, daha yüksek CAR-T hücre zirvesi mRNA ekspresyonunun, daha büyük çalışmalarda daha fazla araştırmayı gerektiren, artan ICANS ve muhtemelen CRS riski ile ilişkili olduğunu göstermektedir. Anahtar Sözcükler Anahtar Kelimeler: Non-Hodgkin lenfoma, Lenfomalar, Neoplazi, Nakil ilişkili toksisite, Kök hücre nakli, Moleküler biyoloji, CAR-T hücre tedavisi
Christian Messerli, Gertrud Wiedemann, Naomi Porret, Michael Nagler, Katja Seipel, Barbara Jeker, Urban Novak, Sacha Zeerleder, Ulrike Bacher, Thomas Pabst. Correlation of Peripheral Chimeric Antigen Receptor T-cell (CAR-T Cell) mRNA Expression Levels with Toxicities and Outcomes in Patients with Diffuse Large B-cell Lymphoma. Turk J Hematol. 2023; 40(3): 187-196
Corresponding Author: Thomas Pabst |
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