Highlights
- •Reporting of chimeric antigen receptor T-cell therapy (CART) on modified intention-to-treat analysis over-estimates efficacy.
- •CART trials often do not report on patients unable to receive intended therapy.
- •A substantial minority of patients on CART trials are unable to receive treatment.
- •On intention-to-treat analysis of CART trials, response rates are lower by 8–12%.
Abstract
Introduction
Chimeric antigen receptor T-cell therapy (CART) has revolutionised treatment of haematological
malignancies; however, current reporting uses a modified intention-to-treat analysis
(mITT) which over-estimates efficacy.
We assessed what proportion of CD19 and B-cell maturation antigen (BCMA) CART trials
report the number of patients not receiving CART after being enrolled by performing
meta-analysis of the mITT and intention-to-treat (iTT) overall response rate (ORR).
Methods
PubMed/MEDLINE, EMBASE and Cochrane databases were searched. All prospective clinical
trials of CD19 and BCMA-targeting CART enrolling two or greater patients from 1st
January 2013 to 1st November 2020 were included.
Results
A total of 28 BCMA CART and 74 CD19 CART trials were identified. These included 10
BCMA CART (35.7%) and 52 (70.2%) CD19 CART trials reporting total number of patients
enrolled and number of patients treated with CART. For this cohort of trials, the
mITT ORR for BCMA CART was 78.0% (95% confidence interval (CI) = 67.0–89.0%), and
the iTT ORR was 70.0% (95% CI = 59.0–80.0%). For CD19 leukaemia CART, the mITT ORR
was 87.2% (95% CI = 83.1–91.2), and the iTT ORR was 74.9 (95% CI = 64.8–85.0). For
CD19 lymphoma CART, the mITT ORR was 70.7% (95% CI = 63.9–77.5), and the iTT ORR was
58.7% (95% CI = 49.7–67.7).
Conclusion
Across BCMA and CD19 CART trials, there is a difference of up to 8–12% in the ORR
between modified and iTT analyses and a paucity of information regarding reasons why
patients did not receive the intended study treatment.
Keywords
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Article info
Publication history
Published online: August 26, 2021
Accepted:
July 27,
2021
Received in revised form:
July 22,
2021
Received:
April 6,
2021
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
