Efficacy and safety of brentuximab vedotin versus standard therapy for cutaneous T-cell lymphoma: A systematic review and meta-analysis

Abstract Introduction: Cutaneous T-cell lymphoma (CTCL) is an uncommon form of non-Hodgkin lymphoma. It is often untreatable, particularly at advanced stages or when it has proven refractory to repeated treatments. Recent research on CTCL has demonstrated promising results in treating the condition with brentuximab vedotin (BV) which is newly-developed antibody-drug conjugate that targets CD30-positive cells. The current study aims to evaluate the efficacy and safety of BV relative to standard therapy (ST) in the treatment of CTCL. Methods: The PubMed, Embase, and Cochrane Library were systematically searched to identify randomized controlled trials (RCTs) comparing BV versus ST in patients with CTCL. Key outcomes include overall response rate lasting for 4 or more months (ORR), complete response rate (CRR), mean progression-free survival (PFS), and overall survival rate (OS). The safety outcome measures included all-cause mortality and the incidence and remission of peripheral neuropathy (PN). Data were pooled using a random-effects model. Statistical heterogeneity was assessed using the I² statistic. A sensitivity analysis was performed for I² greater than 50% by excluding Barta et al., which was consistently identified as a source of heterogeneity due to differing effect estimates. Odds ratio (OR) and mean difference (MD) were reported for dichotomous and continuous outcomes, respectively. Results: We included four RCTs: Barta et al. (2024), Dummer et al. (2020), Kim et al. (2021), and Horwitz et al. (2021), which together comprised a total of 659 patients. ORR, CRR, and mean PFS were reported in 3 studies, and OS was reported in only 2 studies. The efficacy analysis revealed a higher ORR with BV compared to ST with high heterogeneity (I² = 78%). After sensitivity analysis, the pooled ORR analysis demonstrated a consistent direction of effect with no heterogeneity (OR 1.82; 95% CI 1.05–3.17; I² = 0%), although the p-value remained insignificant (p = 0.89). Similarly, we also observed longer mean PFS with BV but with very high heterogeneity (I²=98%). Sensitivity analysis again removed heterogeneity (MD 12.58 months; 95% CI 10.39–14.78, I² = 0%) but retained a non-significant p-value (p = 0.61). CRR also favored BV with high heterogeneity initially (I² = 72%) that resolved after excluding Barta et al. (OR 16.13; 95% CI 3.00–86.68, I² = 0%); though the p-value remained non-significant (p = 0.73). Lastly, a similar trend was observed with the three-year OS, with improved heterogeneity observed after the sensitivity analysis (OR 5.50; 95% CI 5.31–5.68, I² = 0%) but an insignificant p-value (p = 0.38). Upon assessing safety outcomes, we identified no statistically significant difference in all-cause mortality between BV and ST (OR 0.52; 95% CI 0.19–1.41, I² = 77%). BV was associated with a substantially higher risk of PN (OR 33.45; 95% CI 16.43–68.09; p = 0.84; I² = 0%), but among those who developed PN, resolution rates were similar (OR 1.00; 95% CI 0.18–5.57; p = 0.51; I² = 0%); however, this finding is severely limited by the small sample size of the control group (N=6). Conclusion: Although the CI excluded the null value, the p-value remained above the conventional threshold for significance, most likely due to the limited number of included studies and small sample size. Our findings suggest a potential treatment benefit; however, they should be interpreted cautiously. Thus, we suggest further large-scale trials to validate these efficacy outcomes and also identify predictors of PN and develop strategies to mitigate this adverse effect.