Abstract
Background aims
Chimeric antigen receptor T-cell therapy (CART) prolongs survival for patients with
refractory or relapsed lymphoma, yet its efficacy is affected by the tumor burden.
The relevance of tumor kinetics before infusion is unknown. We aimed to study the
prognostic value of the pre-infusion tumor growth rate (TGRpre-BL) for progression-free (PFS) and overall survival (OS).
Methods
Consecutive patients with available pre-baseline (pre-BL) and baseline (BL) computed
tomography or positron emission tomography/computed tomography scan before CART were
included. TGR was determined as change of Lugano criteria-based tumor burden between
pre-BL, BL and follow-up examinations (FU) in relation to days between imaging exams.
Overall response rate (ORR), depth or response (DoR) and PFS were determined based
on Lugano criteria. Multivariate regression analysis studied association of TGR with
ORR and DoR. Proportional Cox regression analysis studied association of TGR with
PFS and OS.
Results
In total, 62 patients met the inclusion criteria. The median TGRpre-BL was 7.5 mm2/d (interquartile range –14.6 mm2/d to 48.7 mm2/d); TGRpre-BL was positive (TGRpre-BL POS) in 58% of patients and negative (TGRpre-BL NEG, indicating tumor shrinkage) in 42% of patients. Patients who were TGRpre-BL POS had a 90-day (FU2) ORR of 62%, a DoR of –86% and a median PFS of 124 days. Patients
who were TGRpre-BL NEG had a 90-day ORR of 44%, DoR of –47% and a median PFS of 105 days. ORR and DoR were
not associated with slower TGR (P = 0.751, P = 0.198). Patients with an increase of TGR from pre-BL over BL to 30-day FU (FU1)
≥100% (TGRpre-BL-to-FU1≥100%) showed a significant association with shorter median PFS (31 days versus 343 days,
P = 0.002) and shorter median OS after CART (93 days versus not reached, P < 0.001), compared with patients with TGRpre-BL-to-FU1<100%.
Conclusions
In the context of CART, differences in pre-infusion tumor kinetics showed minor differences
in ORR, DoR, PFS and OS, whereas the change of the TGR from pre-BL to 30-day FU significantly
stratified PFS and OS. In this patient population of refractory or relapsed lymphomas,
TGR is readily available based on pre-BL imaging, and its change throughout CART should
be explored as a potential novel imaging biomarker of early response.
Key Words
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Article info
Publication history
Published online: April 11, 2023
Accepted:
March 15,
2023
Received:
December 21,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 International Society for Cell & Gene Therapy. Published by Elsevier Inc. All rights reserved.
