Contributions
Abstract: EP743
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
Chimeric antigen receptor T-cell therapy (CART) has revolutionized the treatment of hematological malignancies but is associated with logistical challenges. Current reporting of trials uses a modified intention-to-treat analysis (mITT) which may over-estimate efficacy and limit external validity.
Aims
We assessed what proportion of CD-19 and BCMA CART trials report the number of patients not receiving CART after being enrolled. We performed a meta-analysis of both the mITT and intention-to-treat (iTT) overall response rate (ORR) for CART.
Methods
Four databases were searched (Web of Science/MEDLINE/PubMed, Embase, and Cochrane Registry of Controlled Trials). All prospective clinical trials of CD-19 and BCMA-targeting CART enrolling two or greater patients from January 1st 2013 to November 1st 2020 were included. PRISMA guidelines were used for abstracting data and assessing the quality and validity of the data. Two independent reviewers verified the data and resolved any conflicts. Data was pooled using random effects model. The primary outcome was the proportion of trials reporting number of patients enrolled and those that actually received CART therapy. Secondary outcomes were calculated for trials that reported on the number of patients that dropped out of the study after enrollment and prior to CART administration. Secondary outcomes included ORR on an intention-to-treat analysis incorporating all enrolled patients.
Results
A total of 28 BCMA CART and 100 CD-19 CART trials were identified. Amongst 28 BCMA CART and 100 CD-19 CART trials, only 10 BCMA and 63 CD-19 trials clearly reported on how many patients were enrolled, and how many actually got CART. For this cohort of trials, the mITT ORR for BCMA CART was 78.0% (95% CI= 67.0-89.0%) and iTT ORR was 70.0% (95% CI=59.0-80.0%). For the CD-19 CART, the mITT and iTT ORR were 80.7% (95% CI= 77.0-84.3%) and 69.6% (95% CI=63.7-75.6%), respectively.
Amongst the 10 BCMA trials reporting on the number of patients enrolled but not receiving CART, a total of 395 patients were enrolled and received CART with results of their efficacy reported. An additional 46 patients did not receive CART after enrolling. For six of these patients, the reason for not receiving CART was rapid disease progression necessitating alternate therapy, however, for the remainder of the 40 patients (86.9%), the reasons were not reported.
Amongst the 63 CD-19 trials that reported on the total number of patients enrolled, 32 trials enrolled patients that did not subsequently receive CART, whereas in the other 31 studies all enrolled patients went on to receive CART. In these 63 studies, a total of 2559 patients were enrolled and received CART with efficacy results reported. An additional 286 patients did not receive CART after enrolling. The most common reasons listed were: not reported or other (80, 28%), death (49, 17%), difficulties with manufacturing CART (46, 16%), adverse events (17, 6%), progression of disease or disease-related complications (17, 6%), and infection (11, 4%).
Conclusion
Across BCMA and CD-19 CART trials, there is a difference of 8 – 11% in the overall response rate between modified and intention-to-treat analyses and a paucity of information regarding reasons why patients did not receive the intended study treatment.
Keyword(s): Acute lymphoblastic leukemia, CAR-T, Diffuse large B cell lymphoma, Multiple myeloma
Abstract: EP743
Type: E-Poster Presentation
Session title: Gene therapy, cellular immunotherapy and vaccination - Clinical
Background
Chimeric antigen receptor T-cell therapy (CART) has revolutionized the treatment of hematological malignancies but is associated with logistical challenges. Current reporting of trials uses a modified intention-to-treat analysis (mITT) which may over-estimate efficacy and limit external validity.
Aims
We assessed what proportion of CD-19 and BCMA CART trials report the number of patients not receiving CART after being enrolled. We performed a meta-analysis of both the mITT and intention-to-treat (iTT) overall response rate (ORR) for CART.
Methods
Four databases were searched (Web of Science/MEDLINE/PubMed, Embase, and Cochrane Registry of Controlled Trials). All prospective clinical trials of CD-19 and BCMA-targeting CART enrolling two or greater patients from January 1st 2013 to November 1st 2020 were included. PRISMA guidelines were used for abstracting data and assessing the quality and validity of the data. Two independent reviewers verified the data and resolved any conflicts. Data was pooled using random effects model. The primary outcome was the proportion of trials reporting number of patients enrolled and those that actually received CART therapy. Secondary outcomes were calculated for trials that reported on the number of patients that dropped out of the study after enrollment and prior to CART administration. Secondary outcomes included ORR on an intention-to-treat analysis incorporating all enrolled patients.
Results
A total of 28 BCMA CART and 100 CD-19 CART trials were identified. Amongst 28 BCMA CART and 100 CD-19 CART trials, only 10 BCMA and 63 CD-19 trials clearly reported on how many patients were enrolled, and how many actually got CART. For this cohort of trials, the mITT ORR for BCMA CART was 78.0% (95% CI= 67.0-89.0%) and iTT ORR was 70.0% (95% CI=59.0-80.0%). For the CD-19 CART, the mITT and iTT ORR were 80.7% (95% CI= 77.0-84.3%) and 69.6% (95% CI=63.7-75.6%), respectively.
Amongst the 10 BCMA trials reporting on the number of patients enrolled but not receiving CART, a total of 395 patients were enrolled and received CART with results of their efficacy reported. An additional 46 patients did not receive CART after enrolling. For six of these patients, the reason for not receiving CART was rapid disease progression necessitating alternate therapy, however, for the remainder of the 40 patients (86.9%), the reasons were not reported.
Amongst the 63 CD-19 trials that reported on the total number of patients enrolled, 32 trials enrolled patients that did not subsequently receive CART, whereas in the other 31 studies all enrolled patients went on to receive CART. In these 63 studies, a total of 2559 patients were enrolled and received CART with efficacy results reported. An additional 286 patients did not receive CART after enrolling. The most common reasons listed were: not reported or other (80, 28%), death (49, 17%), difficulties with manufacturing CART (46, 16%), adverse events (17, 6%), progression of disease or disease-related complications (17, 6%), and infection (11, 4%).
Conclusion
Across BCMA and CD-19 CART trials, there is a difference of 8 – 11% in the overall response rate between modified and intention-to-treat analyses and a paucity of information regarding reasons why patients did not receive the intended study treatment.
Keyword(s): Acute lymphoblastic leukemia, CAR-T, Diffuse large B cell lymphoma, Multiple myeloma