Analysis identifies extubation failure risk factors in acute brain injury

9th March 2023

A review suggests extubation failure in acute brain injury is more likely in older patients and following longer mechanical ventilation

In a meta-analysis by Canadian and European researchers it was shown that the risk of extubation failure (EF) in acute brain injury is elevated in older patients and following a longer duration of mechanical ventilation.

Patients with acute brain injury admitted to the intensive care unit (ICU) frequently require mechanical ventilation or other forms of respiratory support, as a consequence of respiratory failure due to loss of airway protective reflexes or decreased respiratory drive. In fact, delaying extubation has been shown to increase the incidence of pneumonia and prolong the length of stay in ICU. However, guidelines designed to support the extubation decision-making process have found limited evidence to support clinicians. Identification of prognostic factors of extubation failure are therefore clearly needed but most evidence on such factors has been derived from non-brain injury patient cohorts.

In the current study, researchers undertook a systematic review and meta-analysis in an effort to identify possible prognostic factors that were associated with EF in acute brain-injured adult patients receiving invasive ventilation in an ICU. The team defined extubation failure as unplanned re-intubation within 72 hours of extubation.

Extubation failure prognostic factors

A total of 21 studies with 3,274 patients and a median age of 53 years were included in the analysis and median incidence of EF was 25%.

The researchers found moderate certainty evidence demonstrating that the risk of EF was associated with increased age (adjusted Odds ratio, aOR = 3, 95% CI 1.78 – 5.07, upper vs lower tertile) as well as a longer duration of mechanical ventilation (aOR = 3.47, 95% CI 1.68 – 7.19, upper vs lower tertile).

In contrast, there was moderate certainty evidence that risk of EF was reduced in the presence of intact cough on the day of extubation (aOR = 0.40, 95% CI 0.28 – 0.57) as well as intact swallow (aOR = 0.34, 95% CI 0.21 – 0.54). However, the certainty of evidence for association with any other factors was either low or very low.

The authors concluded that among adult patients with acute brain injury receiving mechanical ventilation for at least 24 hours, there was moderate certainty evidence to suggest that both older age, a longer duration mechanical ventilation and a lack of intact cough or swallow, were associated with increased risk of extubation failure.

Citation
Taran S et al. Prognostic Factors Associated With Extubation Failure in Acutely Brain-Injured Patients: A Systematic Review and Meta-Analysis. Crit Care Med 2023

Aspirin use benefits reduced by statins in those without atherosclerotic disease

1st March 2023

The benefits of aspirin use in myocardial infarction are offset by statin use in patients without atherosclerotic cardiovascular disease

Aspirin use for the prevention of myocardial infarction (MI) appears to be reduced by concomitant statin use in patients without atherosclerotic cardiovascular disease (ASCVD) without affecting the risk of a major bleed according to a meta-analysis by US researchers.

In 2019, US guidance suggested that aspirin should be used infrequently in the routine primary prevention of ASCVD because of lack of net benefit. More recently, the US Preventative Services Task Force has endorsed these earlier recommendations for primary prevention in adults aged between 40 and 59 with a 10% or higher, 10-year risk of CVD. While historically, aspirin was considered to reduce the risk of an MI, in the context of use with other strategies such as statins, one analysis concluded that the effect of aspirin on myocardial infarction risk was significantly attenuated, whereas its major bleeding and haemorrhagic stroke complications were retained.

For the current meta-analysis, researchers wanted to examine the impact on aspirin use with and without statins, specifically in those without ASCVD but at different levels of risk. The team included a range of risk levels from very low (< 5%) through to very high (> 30%). They included trials where patients were prescribed aspirin and followed for at least 12 months and the team determined the absolute risks for cardiovascular outcomes, major bleeding and mortality over 5 years.

Aspirin use with and without statins

In a total of 16 trials with 171,215 patients with a median age of 64 years (46% women), the use of aspirin alone was associated with a 15% lower risk of a myocardial infarction (risk ratio, RR = 0.85, 95% CI 0.77 – 0.95) although the drug did not reduce mortality. However, the drug lead to a higher risk of major bleeding (RR = 1.48, 95% CI 1.32 – 1.66, p < 0.001).

When considering the absolute benefits, the researched calculated that aspirin monotherapy in patients with a very low ASCVD risk, was likely to lead to 3 fewer myocardial infarctions (MIs) per 10,000 patients but 21 more major bleeds. In contrast, when taken in conjunction with a statin, there would be only 1 less MI but 20 more major bleeds. At the other extreme of ASCVD risk (i.e., > 30%), monotherapy might lead to 49 fewer MIs (but 98 major bleeds) but in combination with a statin, there would be 37 fewer MI’s but 94 major bleeds.

The authors concluded that among adults who did not have ASCVD, statin use with aspirin, appeared to attenuate to some extent aspirin’s clinical benefit but without influencing the bleeding risk, suggesting that the risk of a major bleed from taking aspirin exceeded its benefits across all levels of ASCVD risk.

Citation
Khan SU et al. Aspirin With or Without Statin in Individuals Without Atherosclerotic Cardiovascular Disease Across Risk Categories. JACC Adv 2023

Prior COVID-19 infection provides similar protection as two doses of mRNA vaccine

28th February 2023

A systemic review suggests that the protection afforded by a prior COVID-19 infection is at least as high as that from two doses of a vaccine

Researchers from Washington university in the US, performed a systematic review and meta-analysis finding that the protection afforded by a prior COVID-19 infection was high against re-infection from most pre-omicron variants and remained high against severe disease for all variants and was comparable to the protection from a two-dose vaccination with mRNA vaccines.

To date, several studies have suggested that a previous infection with COVID-19 offers some degree of protection against re-infection. However, studies have included different time periods as well as COVID-19 variants yet there are no analyses that have provided an overview of how the level of protection against re-infection varies over time and in relation to the different variants.

In the current analysis, the US researchers extracted data from studies through to September 2022 that examined the reduction in risk of developing COVID-19 in those with a prior COVID-19 infection compared to those without a previous infection. The data were then analysed to show the effectiveness of a prior infection against several outcomes including the risk of re-infection, symptomatic disease and severe disease based on the variant and time since infection.

Prior COVID-19 infection and re-infection outcomes

A total of 65 studies were included in the analysis from 19 different countries.

The pooled protection against re-infection varied depending on the variant ranging from 82% against delta to 90% against alpha. In contrast, the pooled protection against re-infection with omicron BA.1 was 45.3%. The protection against symptomatic disease was broadly similar, e.g. 85% for delta and 87.2% against alpha and only 44% against omicron BA.1.

The protection against severe infection (i.e., hospitalisation or death) was high for delta (97.2%), slightly lower against alpha (79.6%) but actually also high against omicron BA.1 (81.9%).

The pooled protection against ancestral, alpha and delta variants was initially high at 85.2% after 4 weeks but reduced to 78.6% at 40 weeks. In contrast, protection against re-infection from omicron BA.1 rapidly declined to 36.1% at 40 weeks.

The authors concluded that protection against re-infection was high against most variants pre omicron BA.1 adding that this level of protection was at least equivalent, if not greater than that provided by two-dose mRNA vaccines, which has also been observed in a previous study.

Citation
COVID-19 Forecasting team. Past SARS-CoV-2 infection protection against re-infection: a systematic review and meta-analysis. Lancet 2023

COVID-19 vaccine effectiveness highlights possible need to continue preventative measures

15th February 2023

With COVID-19 vaccine effectiveness reducing over time it is likely that preventative measures such face-masks might still be needed

According to the findings of a systematic review in the Lancet, COVID-19 vaccine effectiveness wanes over time, even following booster doses, indicating that in the longer-term, it may be necessary to continue with preventative measures such as face-mask wearing and physical distancing to help manage the pandemic.

While the introduction of COVID-19 vaccines had an enormous impact on hospitalisations and mortality due to infection with the virus, it has been recognised that induced antibody levels reduce over time. A previous systematic review in 2022 observed that while vaccine efficacy against severe disease only dropped by 10% from one to six months, it reduced by approximately 21% against infection after 6 months and by nearly 25% against symptomatic illness. However, the analysis did not consider the impact of COVID-19 booster doses. As a result, in the current study, researchers examined the effectiveness of vaccination against infection, hospitalisation and death among those who had received a booster dose.

The team examined studies that provided data on vaccine effectiveness for at least 112 days after the primary series of vaccinations or at least 84 days after receipt of a booster dose. They set the primary outcomes of interest as effectiveness against COVID-19 infection, hospitalisation and mortality.

Vaccine effectiveness against COVID-19 outcomes

A total of 68 studies were included in the final analysis.

Overall effectiveness against any strain of COVID-19 reduced from 83% after a primary series of vaccinations to 62% by 112 to 139 days. Similarly, baseline effectiveness against hospitalisation was initially high at 92% but dropped to 79% after 168 – 195 days, as did effectiveness against mortality (91% to 86%) over the same period of time.

Among those who had received booster doses and for which most studies included the omicron variant, vaccine effectiveness against infection was initially 70% but reduced to 43% after 112 days. Similarly, boosted doses against hospitalisation reduced from a baseline of 89% to 71% over the same period of time. The authors reported that there was insufficient data to assess the impact on mortality.

Commenting on their findings, the authors suggested that maintaining COVID-19 prevention behaviours including the wearing of face-masks and physical distancing as well as vaccination may be necessary to reduce transmission of the virus, given how immunity wanes over time. They called for future studies to investigate the effectiveness of simultaneously using multiple approaches such as vaccination and face-masks as transmission preventative strategies.

Citation
Wu N et al. Long-term effectiveness of COVID-19 vaccines against infections, hospitalisations, and mortality in adults: findings from a rapid living systematic evidence synthesis and meta-analysis up to December, 2022. Lancet Respir Med 2023

Analysis finds vitamin D supplementation potentially beneficial for type 2 diabetes

14th February 2023

A meta-analysis suggests that vitamin D supplementation reduces fasting plasma glucose and HbA1c levels in patients with type 2 diabetes

Vitamin D supplementation may be of value to patients with type 2 diabetes, especially if they have suboptimal levels of the vitamin according to a meta-analysis undertaken by US and Iranian researchers.

It has been estimated that in 2017, a staggering 462 million individuals had type 2 diabetes, corresponding to just over 6% of the global population. While there are several therapies available for the management of type 2 diabetes, new treatments will always be needed, given the high prevalence of the disorder. One such potential treatment is vitamin D supplementation and while this is usually given to regulate calcium and phosphorus levels, in recent years, a purported role has been suggested for several diseases. For example, data from the prospective Nurses’ Health study found that higher vitamin D and calcium intake was associated with a 33% lower risk of type 2 diabetes. Nevertheless, studies that involved actual vitamin D supplementation produced mixed findings. For example, one study 6-month trial found that supplementing with the vitamin in patients with type 2 diabetes, failed to affect either insulin sensitivity or secretion. In contrast, an 8-week intervention study demonstrated significant reductions in fasting plasma glucose, insulin and HOMA-IR.

As a result, in the current study, researchers performed a meta-analysis to examine the effect of using the vitamin on indices of glycaemic control including fasting plasma glucose (FPG), HbA1c and HOMA-IR.

Vitamin D supplementation and glycaemic measures

A total of 46 eligible trials were identified including 4,313 patients with type 2 diabetes and a mean age of 56.5 years and of whom 2,164 received the vitamin intervention. The majority of the studies (42) used an oral supplement, whereas in four trials, it was given via intramuscular injection.

The pooled analysis for HbA1c showed a significant reduction compared to placebo for vitamin D (weighted mean difference, WMD = -0.20, p < 0.001). Similarly, there was a significant reduction in FPG (WMD = -0.28 mmol/L, p < 0.001) and HOMA-IR (WMD = -0.42, p = 0.019) in those given vitamin D.

The authors concluded that although vitamin D supplementation had a positive impact of glycaemic indices, they cautioned that the substantial heterogeneity between the included studies, raised the possibility of publication bias.

Citation
Farahmand MA et al. What is the impact of vitamin D supplementation on glycemic control in people with type-2 diabetes: a systematic review and meta-analysis of randomized controlled trails. BMC Endocr Disord 2023

Does CEUS offer greater diagnostic accuracy for abdominal trauma than conventional ultrasound?

9th February 2023

Contrast enhanced ultrasound has greater diagnostic accuracy for abdominal trauma than conventional ultrasound in emergency care settings

The use of contrast enhanced (CE) ultrasound for patients with abdominal trauma prior to computed tomography imaging has a higher diagnostic accuracy in comparison to conventional ultrasound according to the results of a systematic review and meta-analysis by researchers from the Brookdale University Hospital and Medical Center, New York, US.

Undertaking an extended Focused Assessment with Sonography in Trauma (eFAST) is commonly performed as part of the initial assessment of patients who have experienced trauma. Moreover, a systematic review has shown how eFAST serves as a useful bedside tool which is able to rule-in pneumothorax, pericardial effusion as well as intra-abdominal free fluid within a trauma setting but is less useful as a rule-out tool. The diagnostic capability of ultrasound can be improved with the use of a contrast media. In fact, contrast enhanced ultrasound in children has been found to have a comparable performance to both CT and MRI with a very high degree of specificity and hence has the potential to reduce irradiation exposure in paediatric patients. It has also been shown that contrast enhanced ultrasound seems to be both safe and accurate for the identification of abdominal solid organ injuries in children who have experienced a blunt abdominal trauma. Nevertheless, the comparative accuracy of CE ultrasound has not been directly compared to eFAST during the initial trauma assessment and was the subject of the review by the US researchers. The team focused on the use of both ultrasound methods for the initial assessment of patients with abdominal trauma before CT imaging. Paired pooled sensitivity and specificity were used to assess the relative merits of both approaches.

Contrast enhanced ultrasound diagnostic value in abdominal trauma

Following a literature search, a total of 10 eligible studies with 1,359 patients and 30 pairwise comparisons were included in the analysis.

Overall, the paired, pooled sensitivity for CE ultrasound was 0.933 (95% CI 0.917 – 0.948) compared to 0.559 (95% CI 0.527 – 0.591) for conventional ultrasound (p < 0.001). The pooled specificity was also significantly higher (0.995 vs 0.975, p < 0.001). In fact, in sub-group analysis, CE ultrasound was superior to conventional ultrasound for all other areas including the liver, kidneys and adrenals, spleen and for the presence of active bleeding.

Based on these findings, the authors concluded that CE ultrasound was a superior method for differentiating abdominal trauma injuries when used as an initial means of assessment in emergency departments.

Citation
Sutarjono B et al. Is it time to re-think FAST? A systematic review and meta-analysis of Contrast-Enhanced Ultrasound (CEUS) and conventional ultrasound for initial assessment of abdominal trauma. BMC Emerg Med 2023

Skeletal muscle reduces nearly 2% per day upon admission to intensive care

16th January 2023

A systematic review found that skeletal muscle levels reduce by nearly 2% every day during the first week of admission to intensive care

Skeletal muscle loss among critical care patients during the first week of admission to an intensive care unit (ICU) approaches 2 per cent according to the findings of a systematic review and meta-analysis by UK and German researchers.

Critical illness is defined as a state of ill health with vital organ dysfunction and a high risk of imminent death if care is not provided and the potential for reversibility. Moreover, among critically ill patients with sepsis, a considerable number will show signs of severe skeletal muscle wasting and/or ICU-acquired weakness (ICUAW). While the pathophysiology of ICU-AW is incompletely understood, the condition appears to be triggered by critical illness and there is some evidence that skeletal muscle loss is associated with an increased mortality risk. Despite the recognition that skeletal muscle losses occur among critically ill patients, there have been no attempts to summarised the published data on the daily amount of muscle that is lost in ICU patients, which methods are used to monitor muscle size in such patients and on the prevalence of ICU-AW in critically ill patients.

The researchers therefore undertook a systematic review of the topic and searched for studies in which there were at least 20 adult critically ill patients and where the investigators had measured a muscle mass-related variable at two time points during the ICU stay. 

Skeletal muscle loss among ICU patients

The literature search identified 52 relevant studies that included 3251 patients in which 1773 patients had data on on muscle wasting and 1478 on ICU-acquired weakness. Muscle mass was assessed by ultrasound in 85% of studies and the remainder by computed tomography.

During the first week of critical illness, patients were found to have lost an average of -1.75% (95% CI −2.05 −1.45) of their rectus femoris thickness and −2.10% (95% CI −3.17 −1.02) of their rectus femoris cross-sectional area, respectively, every day. In addition, quadriceps muscle thickness decreased by −1.82% (95% CI −2.97 − 0.66) each day and the daily loss in biceps brachii muscle cross-sectional area was −2.23% (95% CI −2.60 − 1.80) and −1.64% (95% CI −3.09, 0.19) for biceps brachii thickness.

Furthermore, the overall prevalence of ICU-acquired weakness was 48% (95% CI 39% – 56%).

The authors concluded that critically ill patients suffer from early and marked muscle wasting, which is about 2% per day but does vary between muscles and depends upon the measurement taken.

Citation
Fazzini B et al. The rate and assessment of muscle wasting during critical illness: a systematic review and meta-analysis. Crit Care 2023

Vaccination found to reduce risk of post-COVID-19 condition

5th January 2023

Vaccination against COVID-19 appears to provide a small but significant protection against the development of post-COVID-19 condition

Receiving a COVID-19 vaccination has been found to reduce the risk of subsequently developing post-COVID-19 condition (or long covid) although the vaccine effectiveness is low according to the findings of a meta-analysis by US researchers.

Vaccine effectiveness is a measure of how well vaccination protects individuals against a condition but differs from the efficacy measured in a trial, because efficacy cannot predict exactly just how effective a vaccine might be in a larger and more variable population. Nevertheless, real-world evidence suggests that some vaccines, such as BNT162b2, have an effectiveness comparable to that reported in phase III clinical trials. Although in practice, many patients make a full recovery after an acute COVID-19 infection, for a minority, there is the continuation or development of other symptoms. The World Health Organisation has described this as ‘Post COVID-19 condition’ and which occurs in individuals with a history of probable or confirmed COVID-19 infection, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis.

While the effectiveness of vaccination against COVID-19 is widely accepted, what is uncertain, is whether vaccination reduces the risk of post–COVID-19 condition. This was the subject of the current study by the US researchers who reviewed the literature on the effectiveness of COVID-19 vaccines for post–COVID-19 condition and pooled the results of published studies to allow for a more precise estimate of effectiveness. The team looked for studies that: involved vaccinated and unvaccinated individuals and evaluated the long-term effectiveness of the COVID-19 vaccine. Post–COVID-19 conditions were defined as a wide range of health symptoms that were present 3 or more weeks after having COVID-19. Any studies without a comparison between vaccinated and unvaccinated individuals (or other vaccinated control group) were excluded. The team calculated the pooled diagnostic odds ratio (DORs) for post–COVID-19 conditions between vaccinated (i.e., those who received at least 1 dose of a COVID-19 vaccine) and unvaccinated individuals.

Vaccination and effectiveness against post-COVID-19 condition

A total of 10 studies with 1,600,830 individuals evaluated the effect of vaccination on post–COVID-19 conditions and of which 6, were included in the meta-analysis. The pooled prevalence of post–COVID-19 conditions was 39.1% among those who were unvaccinated and 37.6% among those who received at least 1 dose.

The pooled DOR for post–COVID-19 conditions among individuals who received at least 1 dose was 0.708 (95% CI 0.69 – 0.73), giving an estimated vaccine effectiveness of 29.2% (95% CI, 27.5%–30.8%).

However, vaccine effectiveness varied depending on whether an individual received the vaccine before or after being infected with COVID-19. For example, effectiveness was 35.3% (95% CI 32.3% – 38.1%) among those who received the COVID-19 vaccine before having COVID-19 but 27.4% (95% CI 25.4% – 29.3%) among those who received it after being infected.

The authors concluded that COVID-19 vaccination before and after having COVID-19 provided a low but statistically significant decrease in post–COVID-19 conditions for the variants circulating during the study period. They added that a more standardised definition of post–COVID-19 conditions was also needed both for research and clinical purposes.

Citation
Marra AR et al. The effectiveness of coronavirus disease 2019 (COVID-19) vaccine in the prevention of post–COVID-19 conditions: A systematic literature review and meta-analysis. Antimicrob Steward Health Epidemiol 2022

Significant placebo response to pain in cannabinoid clinical trials

The placebo response appears to play a significant role in pain reduction in clinical trials assessing a patient’s response to cannabinoids

A placebo response makes a significant contribution to the reduction in pain scores seen in cannabinoid clinical trials according to the findings of a systematic review and meta-analysis by Swedish researchers.

Pain is one of the most common symptoms experienced by patients in different health care settings, often leading to loss of function for the affected individual as well as a decline in their quality of life. Although there are wide range of medicines which act as pain-killers, in recent years, there has been increasing interest in the medical properties of cannabinoids. However, the evidence supporting the value of cannabinoids in pain management is limited. In fact, a 2021 systematic review concluded on how the available evidence neither supports nor refutes claims of efficacy and safety for cannabinoids, cannabis, or cannabis-based medicines in the management of pain. These findings suggest that there may be an important placebo response in such trials and which arise from patients’ positive expectancies. Furthermore, it is believed that different systems and mechanisms trigger placebo effects that highly impact pain processing, clinical outcomes and create a sense of well-being.

But how large is the placebo response in clinical trials examining the role of cannabinoids in the management of pain? This was the key question addressed in the current study where researchers set out to evaluate the size of placebo responses in double-blind randomised clinical trials in which cannabinoids, cannabis, and cannabis-based medicine were compared with placebo in the treatment of clinical pain. The researchers measured the change in pain intensity from before to after treatment, measured as bias-corrected standardised mean difference (Hedges g), which provides an assessment of the effect size. A small effect is represented by a value of 0.2, whereas a medium effect is 0.5 and a large effect 0.8.

Placebo response in cannabinoid trials

The researchers identified a total of 20 eligible trials with 1459 individuals (mean age = 51 years, 56% female). Studies included patients with neuropathic pain and multiple sclerosis.

The effect size of the active drug (cannabinoids) on pain intensity was large (mean Hedges g = 0.95, p  <0 .001). However, pain intensity was associated with a significant reduction in response to placebo, with a moderate to large effect size (mean Hedges g = 0.64, p < 0.001).

In a further analysis, the researchers looked at the media attention paid to these findings and found that this attention was independent of how biased the study was, the extent of the placebo response or how low the treatment effect was.

The authors concluded that placebos contribute significantly to the pain reduction seen in cannabinoid clinical trials. In addition, the positive media attention and wide dissemination possibly leads to high expectations and hence may shape the placebo response in future trials.

Citation
Gedin F et al. Placebo Response and Media Attention in Randomized Clinical Trials Assessing Cannabis-Based Therapies for Pain: A Systematic Review and Meta-analysis. JAMA Netw Open. 2022

Tafasitamab shows best efficacy in refractory diffuse large B-cell lymphoma

21st December 2022

A systematic review and meta‐analysis found that tafasitamab showed the best efficacy in relapsed/refractory diffuse large B-cell lymphoma

According the findings of a systematic review and meta-analysis undertaken by Korean researchers and presented at the American Society of Haematology conference, 2022, tafasitamab showed a trend for best efficacy among failed autologous stem cell transplantation (ASCT) or ineligible relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients.

Diffuse large B cell lymphoma is the most common lymphoma, accounting for about 25% to 30% of all the non-Hodgkin lymphomas and which presents as a rapidly growing mass or enlarging lymph nodes in a nodal or extra-nodal site. Non-Hodgkin lymphomas account for about 80% of all lymphomas and while there are more than 30 subtypes, the common ones are diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma. Although 5-year survival rates range from 60% to 70%, up to 50% of patients become refractory to or relapse after treatment. Moreover, outcomes for refractory or relapsed patients are poor, with one study of 861 patients, 636 of whom had refractory disease, finding that the median overall survival was 6.3 months and that only 20% of patients were alive at 2 years. For patients with relapsed/refractory disease, there are several combination chemotherapy regimens available including tafasitamab-cxix, polatuzumab vedotin-piiq, bendamustine as well as CAR T cell therapies. Nevertheless, the most effective treatment remains to be determined.

In the present study, the Korean researchers performed a systematic review and meta‐analysis to identify prospective phase II or III clinical studies evaluating the efficacy of treatments for ASCT-failed or ineligible relapse/refractory DLBCL patients. They used random effects models to estimate one-year progression-free survival rate, complete remission rate, and subgroup differences. In addition, meta-regression models were performed with adjustment for relevant covariates, particularly the median number of previous lines of systemic therapy and CAR T cell therapy was used as a reference treatment in the meta-regression analysis.

Tafasitamab and one-year progression-free survival

The researchers identified 56 cohorts in 50 studies with 3,544 relapsed/refractory DLBCL patients. For the analysis, treatment regimens were divided into nine groups: CAR T cell therapy, chemotherapy, lenalidomide-based therapy, ibrutinib-based therapy, tafasitamab-based therapy, polatuzumab plus bendamustine and rituximab (pola-BR), loncastuximab, selinexor, and others.

The pooled one-year progression-free survival rate was 0.40 (95% CI 0.35 – 0.46) for CAR T cell therapy, 0.23 (95% CI 0.16 – 0.30) for chemotherapy, 0.28 (95% CI 0.19 – 0.37) for lenalidomide and 0.46 (95% CI 0.37 – 0.56) for tafasitamab.

Although CAR T cell treatment was significantly better than many of the others, in fact, loncastuximab, pola-BR, and tafasitamab were all shown to have no significant difference in efficacy to CAR T cell therapy after adjustment for the median number of prior lines of treatment in the meta-regression analysis.

The authors concluded that tafasitamab showed a trend of best efficacy and that CAR T cell therapy was no more effective than tafasitamab, loncastuximab or pola-BR. However, because of the high level of heterogeneity, the authors called for randomised controlled trials to confirm their findings.

Citation
Kim J et al. Comparison of Several Salvage Treatments of Relapsed/Refractory Large B-Cell Lymphoma Including Chimeric Antigen Receptor T-Cell Therapy: A Systematic Review and Meta‐Analysis. Abstract 2986 ASH conference 2022