Background: While passive immunotherapy has been considered beneficial for patients with severe respiratory viral infections, the treatment of COVID-19 cases with convalescent plasma produced mixed results. Thus, there is a lack of certainty and consensus regarding its effectiveness. This meta-analysis aims to assess the role of convalescent plasma treatment on the clinical outcomes of COVID-19 patients enrolled in randomized controlled trials (RCTs). Methods: A systematic search was conducted in the PubMed database (end-of-search: 29 December 2022) for RCTs on convalescent plasma therapy compared to supportive care\standard of care. Pooled relative risk (RR) and 95% confidence intervals were calculated with random-effects models. Subgroup and meta-regression analyses were also performed, in order to address heterogeneity and examine any potential association between the factors that varied, and the outcomes reported. The present meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: A total of 34 studies were included in the meta-analysis. Per overall analysis, convalescent plasma treatment was not associated with lower 28-day mortality [RR = 0.98, 95% CI (0.91, 1.06)] or improved 28-day secondary outcomes, such as hospital discharge [RR = 1.00, 95% CI (0.97, 1.03)], ICU-related or score-related outcomes, with effect estimates of RR = 1.00, 95% CI (0.98, 1.05) and RR = 1.06, 95% CI (0.95, 1.17), respectively. However, COVID-19 outpatients treated with convalescent plasma had a 26% less risk of requiring hospital care, when compared to those treated with the standard of care [RR = 0.74, 95% CI (0.56, 0.99)]. Regarding subgroup analyses, COVID-19 patients treated with convalescent plasma had an 8% lower risk of ICU-related disease progression when compared to those treated with the standard of care (with or without placebo or standard plasma infusions) [RR = 0.92, 95% CI (0.85, 0.99)] based on reported outcomes from RCTs carried out in Europe. Finally, convalescent plasma treatment was not associated with improved survival or clinical outcomes in the 14-day subgroup analyses. Conclusions: Outpatients with COVID-19 treated with convalescent plasma had a statistically significantly lower risk of requiring hospital care when compared to those treated with placebo or the standard of care. However, convalescent plasma treatment was not statistically associated with prolonged survival or improved clinical outcomes when compared to placebo or the standard of care, per overall analysis in hospitalized populations. This hints at potential benefits, when used early, to prevent progression to severe disease. Finally, convalescent plasma was significantly associated with better ICU-related outcomes in trials carried out in Europe. Well-designed prospective studies could clarify its potential benefit for specific subpopulations in the post-pandemic era.

This meta‐analysis examined the association between minimal residual disease (MRD) negativity and survival outcomes in 15 304 patients with multiple myeloma (MM) enrolled in randomized controlled trials published until June 2, 2024. Overall, there was a significant, negative and strong association between MRD negativity odds ratios and survival hazard ratios (β_PFS = ‐0.20, p < 0.001, β_OS = ‐0.12, p = 0.023). These associations remained significant for newly diagnosed patients (β_PFS = ‐0.35, p < 0.001), and they were consistent but not significant for relapsed/refractory patients (β_PFS = ‐0.06, p = 0.635). Sustained MRD negativity at 1 year was strongly correlated with prolonged PFS (β_PFS = ‐0.30, p < 0.001). In conclusion, this comprehensive meta‐analysis supports MRD as a surrogate for survival in MM.

Background: Multiple myeloma (MM) is an incurable plasma cell dyscrasia with particularly adverse prognosis in relapsed, multi-drug refractory settings. The management of those patients is challenging as treatment options are limited. In this context, bispecific antibodies (BsAbs) have recently emerged as promising therapeutic agents, and several have gained regulatory approval. To better understand their impact in MM landscape, we performed a systematic review and meta-analysis assessing their efficacy and safety in patients with relapsed/refractory MM (RRMM). Methods: A systematic search was conducted in the PubMed, ScienceDirect, Scopus and ClinicalTrials.gov databases for clinical trials investigating BsAbs for RRMM. Pooled estimates in terms of proportions along with 95% confidence intervals were calculated with random-effects models. The present meta-analysis was performed following PRISMA guidelines and was registered in PROSPERO (ID: CRD420251028553). Results: Based on data from six clinical trials involving 850 patients, the pooled overall response and complete response or better rates were 69% and 42%, respectively, whereas the pooled rate of duration of response for at least one year was 71%. The estimated one-year progression-free survival and overall survival were 56% and 72%, respectively. Neutropenia was the most frequently observed severe hematological toxicity, with a pooled incidence of 46%. Grade ≥3 infections occurred in 29%, while any-grade CRS occurred in 69%, as per pooled analysis. Finally, an exploratory minimal residual disease (MRD) analysis in four of the six studies yielded a pooled MRD-negativity rate of 24%. Conclusions: BsAbs demonstrated commendable efficacy in heavily pretreated RRMM patients, in terms of response rates and survival outcomes. However, notable rates of hematologic toxicity, infections, and CRS were recorded. These findings support the clinical utility of BsAbs in RRMM, while highlighting the need for comprehensive toxicity management.

While observation is the current standard of care for smoldering multiple myeloma (sMM), emerging evidence suggests that early therapeutic intervention may delay progression and improve outcomes especially for high-risk patients. A systematic review and meta-analysis of randomized clinical trials was performed according to the PRISMA guidelines in order to evaluate the effect of treatment compared to observation in outcomes of patients with sMM. Five studies (7 articles) involving 844 patients with intermediate or high risk sMM and comparing treatment to observation or placebo were deemed eligible. All studies reported progression-free survival results, with progression defined as time to active myeloma (without high heterogeneity, I² = 42%, p = 0.14). A statistically significant 60% reduced pooled risk for disease progression or death (HR = 0.40, 95%CI:0.29–0.55) was revealed for patients who underwent treatment compared to those who did not. An exploratory sensitivity analysis involving 3 trials with only observation in the control group, revealed a 66% lower risk for disease progression or death (HR = 0.34, 95%CI: 0.21–0.56) for patients in the treatment group compared to the control group. Furthermore, time-to-progression was reported in 3 studies; the pooled effect estimate revealed a statistically significant 58% reduced risk for progression to symptomatic MM (HR = 0.42, 95%CI: 0.29–0.61) for patients who underwent treatment compared to those who did not. Only 2 trials reported mature overall survival outcomes, and the pooled effect estimate showed a 45% lower risk for death (HR = 0.55, 95%CI: 0.37–0.82) for sMM patients who received treatment compared to those on observation. Regarding safety, the odds for serious adverse events for those on treatment was as 3.5 times as high (OR = 3.53, 95%CI: 1.14–10.91) compared to those on observation or placebo. In conclusion, this meta-analysis highlights the significant benefits of early treatment in selected patients with sMM, across key clinical outcomes. However, close monitoring is essential for the management of treatment-related toxicities.

Background: Recently, the addition of anti-CD38 monoclonal antibodies (mAbs) to standard first-line triplet regimens, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD) and dexamethasone, has led to the introduction of quadruplets in clinical practice. Methods: A systematic search was conducted (end-of-search: 9 November, 2024) for clinical trials investigating first-line anti-CD38 mAb-based quadruplets in combination with a PI and an IMiD. Pooled proportions and effect-estimates along with 95% confidence intervals were calculated with common-effect and random-effects models and further subgroup and meta-regression analyses were performed. Results: The pooled 2-, 3- and 4-year progression-free survival (PFS) rates were 89%, 77% and 86%, respectively. Furthermore, patients treated with quadruplets demonstrated a 46% reduced risk for disease progression or death (HR = 0.54, 95% CI: 0.46–0.64) compared to those on triplets. Overall survival (OS) rates were consistently high, ranging from 83% to 96% between different regimens. High rates of deep responses that deepened over time were observed, with the pooled proportion of patients achieving at least complete response being 64%. Importantly, the pooled MRD negativity rate was 62%, whereas patients treated with quadruplet first-line therapy had 2.5 times the odds to be MRD negative at any point compared with those on triplets. Moreover, the odds for sustained 12-month MRD negativity were thrice as much with quadruplets compared to triplets. Finally, while no increase in serious adverse events was observed with quadruplet regimens compared to triplets, a 46% statistically significant increased risk for grade 3–4 neutropenia and thrombocytopenia was observed, along with a 14% increased risk for grade 3–4 infections. Conclusions: The addition of anti-CD38 mAbs to standard triplet regimens has shown particularly favorable outcomes, supporting their integration in the upfront treatment of patients with NDMM. However, close monitoring for hematological toxicity and infections is essential.