Contributions
Abstract: EP1169
Type: E-Poster Presentation
Session title: Quality of life, palliative care, ethics and health economics
Background
Use of chimeric antigen receptor (CAR) T cell therapies for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) was first approved by the United States (US) Food and Drug Administration in 2017 (with lisocabtagene maraleucel approved in 2021) and by the European Medicines Agency in 2018. A growing body of evidence has been published recently on the effectiveness and safety of CAR T cell therapies in the real-world (RW) clinical setting. The landscape of this evidence is of particular interest to clinicians and researchers.
Aims
This systematic literature review was designed to identify and characterize the effectiveness, safety, and quality of life (QOL) of tisagenlecleucel and axicabtagene ciloleucel (axi-cel) in the treatment of R/R LBCL in the RW setting.
Methods
Study eligibility criteria were defined using the PICO (Population, Intervention, Comparators, and Outcomes) framework. Embase, MEDLINE, and relevant conference proceedings were searched from database inception to November 23, 2020. Interventional or observational studies with RW data on specific survival, response, safety, and QOL outcomes in patients with LBCL treated with tisagenlecleucel and axi-cel were included. Study quality was assessed using the Newcastle-Ottawa Scale for non-randomized studies.
Results
After study selection, 68 publications pertaining to 67 unique studies were included, comprising 21 full-text articles and 46 conference abstracts. The majority of the studies were conducted in the US (n=49), followed by the United Kingdom (n=6), Germany (n=6), France (n=4), Spain (n=1), and the US and Canada (n=1). Fifty-two (78%) studies had a sample size of <100 patients. Ten (15%) studies had >1-year follow-up, 37 (55%) had ≤6-month follow-up. Median age ranged from 50–72 years, with median or mean prior lines of therapy ranging from 3–5. Diffuse LBCL (de novo) was the most common disease histology. Use of bridging therapy varied widely from 2%–98% where reported (17 studies). Overall response rates and complete response rates ranged from 32%–84% and 12%–80%, respectively, at 3 months. Median progression-free survival (PFS) ranged from 0.8–13.8 months; median overall survival (OS) ranged from 7.9–35.0 months. PFS at 6 and 12 months ranged from 29%–60% and 20%–47%, respectively; OS ranged from 50%–100% and 56%–80%, respectively. Cytokine release syndrome (CRS) and neurological events (NEs) were reported in 49 (72%) and 47 (69%) studies, respectively. While synthesis of CRS and NE rates was limited by differences in data collection between studies, the reported rates of grade ≥3 CRS and NEs ranged from 0%–43% and 3%–41%, respectively. Only 1 study of 29 patients reported QOL outcomes (Short Form-36 QOL questionnaire), in which authors observed nonsignificant (P > .05) improvements from baseline to 90 days post-treatment with axi-cel in both the physical health and mental health components.
Conclusion
The RW evidence on the effectiveness and safety of commercially available CAR T cell therapies is growing, and a large number of observational studies on axi-cel and tisagenlecleucel in LBCL have been conducted, particularly those investigating axi-cel. The RW evidence suggests CAR T cell therapy is generally effective, based on survival and response outcomes, and safety is similar to that of clinical trials. Additionally, data on QOL are severely limited. Future prospective RW studies with large populations and incorporation of patient-reported outcomes are warranted.
Keyword(s): CAR-T, Diffuse large B cell lymphoma, Systematic review
Abstract: EP1169
Type: E-Poster Presentation
Session title: Quality of life, palliative care, ethics and health economics
Background
Use of chimeric antigen receptor (CAR) T cell therapies for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) was first approved by the United States (US) Food and Drug Administration in 2017 (with lisocabtagene maraleucel approved in 2021) and by the European Medicines Agency in 2018. A growing body of evidence has been published recently on the effectiveness and safety of CAR T cell therapies in the real-world (RW) clinical setting. The landscape of this evidence is of particular interest to clinicians and researchers.
Aims
This systematic literature review was designed to identify and characterize the effectiveness, safety, and quality of life (QOL) of tisagenlecleucel and axicabtagene ciloleucel (axi-cel) in the treatment of R/R LBCL in the RW setting.
Methods
Study eligibility criteria were defined using the PICO (Population, Intervention, Comparators, and Outcomes) framework. Embase, MEDLINE, and relevant conference proceedings were searched from database inception to November 23, 2020. Interventional or observational studies with RW data on specific survival, response, safety, and QOL outcomes in patients with LBCL treated with tisagenlecleucel and axi-cel were included. Study quality was assessed using the Newcastle-Ottawa Scale for non-randomized studies.
Results
After study selection, 68 publications pertaining to 67 unique studies were included, comprising 21 full-text articles and 46 conference abstracts. The majority of the studies were conducted in the US (n=49), followed by the United Kingdom (n=6), Germany (n=6), France (n=4), Spain (n=1), and the US and Canada (n=1). Fifty-two (78%) studies had a sample size of <100 patients. Ten (15%) studies had >1-year follow-up, 37 (55%) had ≤6-month follow-up. Median age ranged from 50–72 years, with median or mean prior lines of therapy ranging from 3–5. Diffuse LBCL (de novo) was the most common disease histology. Use of bridging therapy varied widely from 2%–98% where reported (17 studies). Overall response rates and complete response rates ranged from 32%–84% and 12%–80%, respectively, at 3 months. Median progression-free survival (PFS) ranged from 0.8–13.8 months; median overall survival (OS) ranged from 7.9–35.0 months. PFS at 6 and 12 months ranged from 29%–60% and 20%–47%, respectively; OS ranged from 50%–100% and 56%–80%, respectively. Cytokine release syndrome (CRS) and neurological events (NEs) were reported in 49 (72%) and 47 (69%) studies, respectively. While synthesis of CRS and NE rates was limited by differences in data collection between studies, the reported rates of grade ≥3 CRS and NEs ranged from 0%–43% and 3%–41%, respectively. Only 1 study of 29 patients reported QOL outcomes (Short Form-36 QOL questionnaire), in which authors observed nonsignificant (P > .05) improvements from baseline to 90 days post-treatment with axi-cel in both the physical health and mental health components.
Conclusion
The RW evidence on the effectiveness and safety of commercially available CAR T cell therapies is growing, and a large number of observational studies on axi-cel and tisagenlecleucel in LBCL have been conducted, particularly those investigating axi-cel. The RW evidence suggests CAR T cell therapy is generally effective, based on survival and response outcomes, and safety is similar to that of clinical trials. Additionally, data on QOL are severely limited. Future prospective RW studies with large populations and incorporation of patient-reported outcomes are warranted.
Keyword(s): CAR-T, Diffuse large B cell lymphoma, Systematic review