OBJECTIVES: Approximately half of aALL patients experience relapse/refractory disease after first-line, and SoC treatments beyond first-line are limited. To improve the understanding of overall effectiveness beyond first-line, this study aims to estimate OCRR (CR + CR with incomplete hematologic recovery) and CR in R/R aALL across approved and recommended treatments.

METHODS: A meta-analysis was conducted using clinical trials in R/R aALL patients identified through a systematic literature review (SLR) in line with prevailing guidelines. Included publications were evaluated for eligibility in the meta-analysis (i.e. FDA/EMA-approved, NCCN/ESMO-recommended treatments, reporting OCRR or CR, adults ≥18 yo, clinical trial design). The best fitting model (random effects) was used for estimation of pooled CR and OCRR. The base case analysis considered all studies that met the eligibility criteria. In a scenario analysis, studies representing more severe baseline disease profiles (i.e. ≥50% with 2+ lines of prior treatment, heavy bone marrow (BM) blasts [defined as median % blasts >50% or more than 50% of patients have >50% blasts]) were pooled.

RESULTS: The SLR identified 68 publications eligible for inclusion. Lack of reporting on OCRR or CR results was the main reason for exclusion. In the base case, 11 and 14 trials (salvage chemotherapy, blinatumomab and inotuzumab) could be included for the OCRR and CR analysis, respectively. The pooled patient characteristics were: median age 42 yo, 57% ≥3 prior therapies, median BM blasts 72%. The best fitted model resulted in an OCRR of 51% (95%CI: 42%-59%) and a CR of 38% (95%CI: 28%-49%) across treatments. In the scenario analysis, the pooled OCRR and CR were 47% (95%CI: 37%-57%) and 30% (95%CI: 23%-36%), respectively.

CONCLUSIONS: SoC for R/R aALL patients comprises multiple therapeutic options, none providing satisfactory response. The meta-analysis confirms the need for better treatment options.