Page 103 - Haematologica May 2022

Non-Hodgkin Lymphoma
Toxicity and efficacy of chimeric antigen receptor T-cell therapy in patients with diffuse large B-cell lymphoma above the age of 70 years compared to younger patients – a matched control multicenter cohort study
Ron Ram,1,2 Sigal Grisariu,3 Liat Shargian-Alon,2,4 Odelia Amit,1,2 Yaeli Bar-On,1,2 Polina Stepensky,3 Moshe Yeshurun,2,4 Batia Avni,3 David Hagin,2,5 Chava Perry,1,2 Ronit Gurion,2,4 Nadav Sarid,1,2 Yair Herishanu,1,2 Ronit Gold,1 Chen Glait-Santar,1,2 Sigi Kay1,2 and Irit Avivi1,2
1BMT Unit, Tel Aviv (Sourasky) Medical Center, Tel Aviv; 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv; 3Department of Bone Marrow Transplantation Hadassah University Hospital and The Hebrew University of Jerusalem, Faculty of Medicine, Jerusalem; 4Institute of Hematology, Rabin Medical Center, Petach Tikva and 5Immunology Unit, Tel Aviv (Sourasky) Medical Center, Tel Aviv, Israel
ABSTRACT
Data regarding efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in the elderly, geriatric population are insuf- ficient. In 2019, tisagenlecleucel and axicabtagene-ciloleucel were commercially approved for relapsed/refractory diffuse large B-cell lym- phoma. From May 2019 onwards, 47 relapsed/refractory diffuse large B- cell lymphoma patients, ≥70 years underwent lymphopharesis in three Israeli centers. Elderly (n=41, mean age 76.2 years) and young (n=41, mean age 55.4 years) patients were matched based on ECOG perform- ance status and lactose dehydrogenase levels. There were no differences in CD4/CD8 ratio (P=0.94), %CD4 naive (P=0.92), %CD8 naive (P=0.44) and exhaustion markers (both HLA-DR and PD-1) between CAR-T cell products in both cohorts. Forty-one elderly patients (87%) received CAR-T cell infusion. There were no differences in the incidence of grade ≥3 cytokine-release-syndrome (P=0.29), grade≥3 neurotoxicity (P=0.54), and duration of hospitalization (P=0.55) between elderly and younger patients. There was no difference in median D7-CAR-T cell expansion (P=0.145). Response rates were similar between the two groups (complete response 46% and partial response 17% in the elderly group, P=0.337). Non-relapse mortality at 1 and 3 months was 0 in both groups. With a median follow-up of 7 months (range, 1.3-17.2 months), 6- and 12-months progression-free and overall survival in elderly patients were 39% and 32%, and 74% and 69%, respectively. EORTC QLQ-C30 questionnaires, obtained at 1 month, showed worsening of disability and cancer-related-symptoms in elderly versus younger patients. We con- clude that outcomes of CAR-T cell therapy are comparable between eld- erly, geriatric and younger patients, indicating that age as per se should not preclude CAR-T cell administration. Longer rehabilitation therapy is essential to improve disabilities and long-term symptoms.
Introduction
The median age of diagnosis for diffuse large cell B-cell lymphoma (DLBCL), the most common subtype of aggressive lymphoma, is 66 years with approximately 40% of the patients above the age of 70 years (SEER cancer statistics). Advanced age is a major risk factor for relapse and death in patients with DLBCL.1 A recent study, evaluating the real-world outcome of DLBCL patients, reported a 52% complete remission rate in patients older than 65 years. However 22% of these complete responders subsequently experienced disease relapse, indicating that almost two thirds of elderly DLBCL patients will eventually require salvage therapy.2 Although
Ferrata Storti Foundation
Haematologica 2022 Volume 107(5):1111-1118
Correspondence:
RON RAM
ronram73@gmail.com
Received: January 8, 2021. Accepted: July 1, 2021. Pre-published: July 8, 2021.
https://doi.org/10.3324/haematol.2021.278288 ©2022 Ferrata Storti Foundation
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