Contributions
Abstract: PB1430
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
A substantial proportion of people with diffuse large B-cell lymphoma (DLBCL) experience relapse or are refractory to therapy (r/r). With a median overall survival below 6-12 months, the prognosis of those who relapse or are refractory to advanced lines of treatment or those who are ineligible for autologous stem cell transplantation is very poor. For these individuals, chimeric antigen receptor (CAR)-T cell therapy provides a promising treatment option.
Aims
To assess the benefits and harms of CAR-T cell therapy for people with r/r DLBCL.
Methods
In accordance with a published Cochrane protocol, we systematically searched CENTRAL, MEDLINE, Embase, conference proceedings, trial registries and databases for prospectively planned trials – beginning with randomised controlled trials (RCTs) – evaluating CAR-T cells for people with r/r DLBCL until September 2020. We excluded trials with less than 10 participants with r/r DLBCL and trials with less than 70% of participants with r/r DLBCL, unless respective data were reported separately. Two review authors extracted data and assessed potential risk of bias independently. As we did not identify any controlled trials, we did not meta-analyse data. We used the GRADE approach to assess the certainty of the evidence for prioritised outcomes.
Results
We included 13 uncontrolled trials and identified 38 ongoing trials, three of which are RCTs to be completed between 2022 and 2025. We judged all included trials to be at high risk of bias. Primarily due to the lack of a control group, study limitations and restricted applicability, our certainty in the evidence was very low for all outcomes.
Overall survival (OS) was reported by eight studies with substantial variation in sample size, duration of follow-up and proportion of people with DLBCL. Four studies reported 12-month survival rates of 48-59%, and one study reported an OS rate of 50.5% at 24 months (very low-certainty evidence). Two studies described improvements of quality of life over time (very low-certainty evidence). Five studies reported that a vast majority of participants experienced adverse events (AEs) (99-100% any grade, 68-98% grade ≥3; very low-certainty evidence). According to three studies, 56-68% of participants had serious AEs, while in one study, no serious AEs occurred (very low-certainty evidence). Various criteria were used by 11 studies to report Cytokine release syndrome (CRS). In five studies, 42-100% of participants had CRS according to criteria described by Lee 2014 (very low-certainty evidence). Nine studies reported progression-free survival (PFS), disease-free survival or relapse-free survival at any time of follow-up. Twelve-month PFS rates between 44-75% were reported by four studies. In one study, relapse-free survival rates remained at 64% at both 12, and 18 months (very low-certainty evidence). All 13 studies provided data on complete response (CR). Three studies reported 6-month CR rates between 40-45% (very low-certainty evidence).
Conclusion
The available evidence on the benefits and harms of CAR-T cell therapy for people with r/r DLBCL is limited, especially due to the absence of comparative clinical trials. Given the uncertainty in the current evidence, the risk of substantial and potentially life-threatening complications that require supplementary treatment and the large number of ongoing investigations, it is critical to continue evaluating how the evidence on this novel therapy will evolve.
Keyword(s): CAR-T, DLBCL, Systematic review
Abstract: PB1430
Type: Publication Only
Session title: Aggressive Non-Hodgkin lymphoma - Clinical
Background
A substantial proportion of people with diffuse large B-cell lymphoma (DLBCL) experience relapse or are refractory to therapy (r/r). With a median overall survival below 6-12 months, the prognosis of those who relapse or are refractory to advanced lines of treatment or those who are ineligible for autologous stem cell transplantation is very poor. For these individuals, chimeric antigen receptor (CAR)-T cell therapy provides a promising treatment option.
Aims
To assess the benefits and harms of CAR-T cell therapy for people with r/r DLBCL.
Methods
In accordance with a published Cochrane protocol, we systematically searched CENTRAL, MEDLINE, Embase, conference proceedings, trial registries and databases for prospectively planned trials – beginning with randomised controlled trials (RCTs) – evaluating CAR-T cells for people with r/r DLBCL until September 2020. We excluded trials with less than 10 participants with r/r DLBCL and trials with less than 70% of participants with r/r DLBCL, unless respective data were reported separately. Two review authors extracted data and assessed potential risk of bias independently. As we did not identify any controlled trials, we did not meta-analyse data. We used the GRADE approach to assess the certainty of the evidence for prioritised outcomes.
Results
We included 13 uncontrolled trials and identified 38 ongoing trials, three of which are RCTs to be completed between 2022 and 2025. We judged all included trials to be at high risk of bias. Primarily due to the lack of a control group, study limitations and restricted applicability, our certainty in the evidence was very low for all outcomes.
Overall survival (OS) was reported by eight studies with substantial variation in sample size, duration of follow-up and proportion of people with DLBCL. Four studies reported 12-month survival rates of 48-59%, and one study reported an OS rate of 50.5% at 24 months (very low-certainty evidence). Two studies described improvements of quality of life over time (very low-certainty evidence). Five studies reported that a vast majority of participants experienced adverse events (AEs) (99-100% any grade, 68-98% grade ≥3; very low-certainty evidence). According to three studies, 56-68% of participants had serious AEs, while in one study, no serious AEs occurred (very low-certainty evidence). Various criteria were used by 11 studies to report Cytokine release syndrome (CRS). In five studies, 42-100% of participants had CRS according to criteria described by Lee 2014 (very low-certainty evidence). Nine studies reported progression-free survival (PFS), disease-free survival or relapse-free survival at any time of follow-up. Twelve-month PFS rates between 44-75% were reported by four studies. In one study, relapse-free survival rates remained at 64% at both 12, and 18 months (very low-certainty evidence). All 13 studies provided data on complete response (CR). Three studies reported 6-month CR rates between 40-45% (very low-certainty evidence).
Conclusion
The available evidence on the benefits and harms of CAR-T cell therapy for people with r/r DLBCL is limited, especially due to the absence of comparative clinical trials. Given the uncertainty in the current evidence, the risk of substantial and potentially life-threatening complications that require supplementary treatment and the large number of ongoing investigations, it is critical to continue evaluating how the evidence on this novel therapy will evolve.
Keyword(s): CAR-T, DLBCL, Systematic review