The Impact of Induction Regimens on Clinical Outcomes in Double and Triple-Hit Lymphoma: A Meta-Analysis of Comparative Studies

Abstract

Background: Double and triple hit lymphomas (DTHL) are aggressive high-grade lymphomas that harbor translocations of MYC and BCL2 and/or BCL6. They constitute 6-14% of all aggressive B-cell lymphoma and have been associated with poor clinical outcomes. Though there is no established standard therapy for DTHL, induction chemotherapy vacillates between R-CHOP-like regimens, R-EPOCH, or more dose-intense regimens (DI) such as R-hyperCVAD/MA and CODOX-M/IVAC with or without consolidation with stem cell transplant. Currently, there are no randomized trials establishing a standard induction regimen. Furthermore, several retrospective studies reported conflicting results regarding the comparative benefits of these various induction approaches. Therefore, we conducted this meta-analysis to evaluate the impact of induction chemotherapy regimens on the clinical outcomes of DTHL. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of DTHL, comparative studies of induction chemotherapy regimens, and studies that reported overall (OS) and progression-free (PFS) survival. Studies that reported the aggregate outcome of mixed samples of DTHL and other lymphomas were excluded. A meta-analysis using the fixed effects and random effects models was conducted. Results: Seven retrospective comparative studies with a total of 1433 patients were included. The median age was 62 years, and the median follow-up was 27.5 months. DI regimens were associated with better PFS than R-CHOP-like regimens (HR = 0.81, 95%CI 0.66-0.99, p = 0.039) but without improved OS. R-EPOCH, including R-DA-EPOCH, regimens were associated with better PFS than R-CHOP-like regimens (HR = 0.62, 95%CI 0.43-0.91, p = 0.013) but without improved OS. R-HyperCVAD/MA regimen was associated with better PFS compared to R-CHOP-like regimens (HR = 0.64, 95%CI 0.47-0.87, p = 0.005) but without improved OS. Conclusions: This is the first and largest meta-analysis to show that induction DI regimens, in general, and R-EPOCH and R-HyperCVAD/MA regimens, in particular, are associated with better PFS than R-CHOP-like regimens in patients with DTHL. However, this advantage did not translate into a survival benefit.