Turk J Hematol. 2023; 40(3): 187-196 | DOI: 10.4274/tjh.galenos.2023.2023.0136

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

Christian Messerli¹, Gertrud Wiedemann², Naomi Porret², Michael Nagler³, Katja Seipel⁴, Barbara Jeker¹, Urban Novak¹, Sacha Zeerleder², Ulrike Bacher², Thomas Pabst^1
1University 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

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Diffüz Büyük B-hücreli Lenfomalı Hastalarda Periferik Kimerik Antijen Reseptör T-hücresi (CAR-T Hücresi) mRNA Ekspresyon Düzeylerinin Toksisiteler ve Sonuçlarla Korelasyonu

Christian Messerli¹, Gertrud Wiedemann², Naomi Porret², Michael Nagler³, Katja Seipel⁴, Barbara Jeker¹, Urban Novak¹, Sacha Zeerleder², Ulrike Bacher², Thomas Pabst^1
1University 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

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