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. 2023 Aug 30;15(17):4334.
doi: 10.3390/cancers15174334.

The Dutch CAR-T Tumorboard Experience: Population-Based Real-World Data on Patients with Relapsed or Refractory Large B-Cell Lymphoma Referred for CD19-Directed CAR T-Cell Therapy in The Netherlands

Anne M Spanjaart  1   2   3 , Elise R A Pennings  1   2   3   4 , Pim G N J Mutsaers  5 , Suzanne van Dorp  6 , Margot Jak  7 , Jaap A van Doesum  8 , Janneke W de Boer  8 , Anne G H Niezink  9 , Milan Kos  2   10 , Joost S P Vermaat  11 , Aniko Sijs-Szabo  11 , Marjolein W M van der Poel  12 , Inger S Nijhof  2   13   14 , Maria T Kuipers  2   13 , Martine E D Chamuleau  2   13 , Pieternella J Lugtenburg  5 , Jeanette K Doorduijn  5 , Yasmina I M Serroukh  5 , Monique C Minnema  7 , Tom van Meerten  8 , Marie José Kersten  1   2   3 ; Dutch CAR-T Tumorboard Consortium
Affiliations

The Dutch CAR-T Tumorboard Experience: Population-Based Real-World Data on Patients with Relapsed or Refractory Large B-Cell Lymphoma Referred for CD19-Directed CAR T-Cell Therapy in The Netherlands

Anne M Spanjaart et al. Cancers (Basel). .

Abstract

The real-world results of chimeric antigen receptor T-cell (CAR-T) therapy for patients with relapsed/refractory (R/R) large B-cell lymphoma (LBCL) substantially differ across countries. In the Netherlands, the CAR-T tumorboard facilitates a unique nationwide infrastructure for referral, eligibility assessment and data collection. The aim of this study was to evaluate real-world outcomes of axicabtagene ciloleucel (axi-cel) in the Dutch population, including the thus-far underreported effects on health-related quality of life (HR-QoL). All patients with R/R LBCL after ≥2 lines of systemic therapy referred for axi-cel treatment between May 2020-May 2022 were included (N = 250). Of the 160 apheresed patients, 145 patients received an axi-cel infusion. The main reason for ineligibility was rapidly progressive disease. The outcomes are better or at least comparable to other studies (best overall response rate: 84% (complete response: 66%); 12-month progression-free-survival rate and overall survival rate: 48% and 62%, respectively). The 12-month NRM was 5%, mainly caused by infections. Clinically meaningful improvement in several HR-QoL domains was observed from Month 9 onwards. Expert-directed patient selection can support effective and sustainable application of CAR-T treatment. Matched comparisons between cohorts will help to understand the differences in outcomes across countries and select best practices. Despite the favorable results, for a considerable proportion of patients with R/R LBCL there still is an unmet medical need.

Keywords: CAR T-cell therapy; LBCL; outcomes; real-world data.

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Conflict of interest statement

M.J. received honoraria from Kite/Gilead and BMS/Celgene, has a consulting/advisory role for Janssen and received research funding from Novartis. A.G.H.N. discloses conflicts of interest all outside of the submitted work with: IBA, PHILIPS, MIRADA, RaySearch, Siemens, Elekta, Leonie and Genentech. M.W.M.v.d.P. received honoraria from Kite/Gilead and Takeda. M.T.K. has a consulting/advisory role for CellPoint. M.E.D.C. has a consulting/advisory role for AbbVie and Novartis and received research funding from BMS/Celgene, Gilead and GenMAb. P.J.L. received honoraria for advisory boards from Genmab, AbbVie, Roche, Regeneron and Incyte, has a consulting role for Y-mAbs Therapeutics, is in the speakers’ bureau for Lilly and AbbVie, and has received travel support from Celgene and research funding from Takeda and Servier. M.C.M. has a consulting/advisory role for Janssen Cilag, CDR life, GSK and the speakers’ bureau for Doen, Janssen Cilag, BMS, WebMD global. T.v.M. has served on the advisory boards of Kite/Gilead, Celgene/BMS, Jansen and Lilly and received research funding from Kite/Gilead, Celgene/BMS, Genentech and Siemens. M.J.K. received honoraria from and performed in a consulting/advisory role for BMS/Celgene, Kite, a Gilead Company, Miltenyi Biotec, Novartis and Roche, as well as receiving research funding from Kite, a Gilead Company, Roche, Takeda, and Celgene and travel support from Kite, a Gilead Company, Miltenyi Biotec, Novartis, and Roche (all to institutions). A.M.S., E.R.A.P., P.G.N.J.M., S.v.D., J.A.v.D., J.W.d.B., M.K., J.S.P.V., A.S.-S., I.S.N., J.K.D. and Y.I.M.S. declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flowchart of national patient selection for commercially available CD19-directed CAR-T therapy: all patients referred to the Dutch CAR-T tumorboard between May 2020 until May 2022 and reasons for ineligibility. Abbreviations: CNS: central nervous system, ECOG: Eastern Cooperative Oncology Group, LBCL: large B-cell lymphoma.
Figure 2
Figure 2
Time path from indication for CD19-directed CAR-T therapy to CAR-T infusion (median duration in days (IQR)).
Figure 3
Figure 3
Bridging therapy used in CAR-T infused patients. Abbreviations: CR: complete response, PD: progressive disease, PR: partial response, SD: stable disease.
Figure 4
Figure 4
Best overall response rates to CAR-T. Abbreviations: CR: complete response, NA: not available, ORR: overall response rate, PD: progressive disease, PR: partial response, SD: stable disease.
Figure 5
Figure 5
Response to axicabtagene ciloleucel over time in the first year post-infusion until progression or death.
Figure 6
Figure 6
Overall survival and progression-free survival from CAR-T infusion for all CAR-T infused patients (A,B) and stratified per best response (C,D). Abbreviations: CR: complete response, NR: no response, PR: partial response.
Figure 7
Figure 7
Flowchart describing the proportion of referred R/R LBCL patients with the appropriate indication as per the product registration label who benefit from axicabtagene ciloleucel. Abbreviations: Axi-cel: axicabtagene ciloleucel, LBCL: large B-cell lymphoma, R/R: relapsed/refractory.
Figure 8
Figure 8
Mean changes from baseline in HR-QoL domain scores over time for EQ-5D-5L VAS score (A), EORTC QLQ-C30 global health status/quality of life (B), EORTC QLQ-C30 emotional functioning (C), EORTC QLQ-C30 physical functioning (D).
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