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. 2024 Sep;13(17):e70138.
doi: 10.1002/cam4.70138.

Several factors that predict the outcome of large B-cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T-cell therapy can be identified before cell administration

Alice Sýkorová  1 , František Folber  2 , Kamila Polgárová  3 , Heidi Móciková  4 , Juraj Ďuraš  5 , Kateřina Steinerová  6 , Aleš Obr  7 , Adriana Heindorfer  8 , Miriam Ladická  9 , Ľubica Lukáčová  10 , Erika Čellárová  11 , Ivana Plameňová  12 , David Belada  1 , Andrea Janíková  2 , Marek Trněný  3 , Tereza Jančárková  4 , Vít Procházka  7 , Andrej Vranovský  9 , Margaréta Králiková  11 , Jan Vydra  13 , Lukáš Smolej  1 , Ľuboš Drgoňa  9 , Martin Sedmina  11 , Eva Čermáková  14 , Robert Pytlík  13
Affiliations

Several factors that predict the outcome of large B-cell lymphoma patients who relapse/progress after chimeric antigen receptor (CAR) T-cell therapy can be identified before cell administration

Alice Sýkorová et al. Cancer Med. 2024 Sep.

Abstract

Aim: The aim of this study was to analyse the outcomes of patients with large B-cell lymphoma (LBCL) treated with chimeric antigen receptor T-cell therapy (CAR-Tx), with a focus on outcomes after CAR T-cell failure, and to define the risk factors for rapid progression and further treatment.

Methods: We analysed 107 patients with LBCL from the Czech Republic and Slovakia who were treated in ≥3rd-line with tisagenlecleucel or axicabtagene ciloleucel between 2019 and 2022.

Results: The overall response rate (ORR) was 60%, with a 50% complete response (CR) rate. The median progression-free survival (PFS) and overall survival (OS) were 4.3 and 26.4 months, respectively. Sixty-three patients (59%) were refractory or relapsed after CAR-Tx. Of these patients, 39 received radiotherapy or systemic therapy, with an ORR of 22% (CR 8%). The median follow-up of surviving patients in whom treatment failed was 10.6 months. Several factors predicting further treatment administration and outcomes were present even before CAR-Tx. Risk factors for not receiving further therapy after CAR-Tx failure were high lactate dehydrogenase (LDH) levels before apheresis, extranodal involvement (EN), high ferritin levels before lymphodepletion (LD) and ECOG PS >1 at R/P. The median OS-2 (from R/P after CAR-Tx) was 6.7 months (6-month 57.9%) for treated patients and 0.4 months (6-month 4.2%) for untreated patients (p < 0.001). The median PFS-2 (from R/P after CAR-Tx) was 3.2 months (6-month 28.5%) for treated patients. The risk factors for a shorter PFS-2 (n = 39) included: CRP > limit of the normal range (LNR) before LD, albumin < LNR and ECOG PS > 1 at R/P. All these factors, together with LDH > LNR before LD and EN involvement at R/P, predicted OS-2 for treated patients.

Conclusion: Our findings allow better stratification of CAR-Tx candidates and stress the need for a proactive approach (earlier restaging, intervention after partial remission achievement).

Keywords: CAR T‐cell failure; outcomes of patients after CAR T‐cell therapy failure; relapsed/refractory large B‐cell lymphoma; risk factors for CAR T‐cell therapy failure.

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Figures

FIGURE 1
FIGURE 1
Progression‐free survival (n = 107).
FIGURE 2
FIGURE 2
Treatment modalities and response after first‐line postCAR T‐cell therapy. BTK, Bruton kinase; CAR, chimeric antigen receptor; CHT, chemotherapy; CR, complete remission; NA, not available; pola‐BR, polatuzumab vedotin‐bendamustine + rituximab; PD1, programmed death 1; PD, progressive disease; PR, partial remission; R, rituximab; SD, stable disease.
FIGURE 3
FIGURE 3
Overall survival (OS‐2; n = 63)—treated vs. untreated patients.
FIGURE 4
FIGURE 4
Progression‐free survival (PFS treated‐2;A) and overall survival (OS treated‐2; B) of patients who failed to respond to CAR T‐cell therapy (n = 39).
See this image and copyright information in PMC

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