RECENT results from a systematic review and meta-analysis demonstrated that the status of measurable residual disease (MRD) might be a suitable endpoint in clinical trials predicting progression-free survival (PFS) among patients with chronic lymphocytic leukaemia (CLL). MRD refers to residual cancer cells at low levels undetectable by standard pathological analysis. The study aimed to establish whether MRD status could serve as a reliable surrogate endpoint for clinical outcomes in targeted therapies, potentially improving trial efficiency and accelerating drug development processes.
The study analysed data from 11 prospective clinical trials involving 2765 CLL patients treated with targeted agents or obinutuzumab-based therapy. The meta-analysis revealed a significant association between achieving undetectable MRD (uMRD) at 0.01% and improved PFS. Patients who achieved uMRD demonstrated a substantially lower hazard ratio (HR) for progression compared to those with detectable MRD (HR, 0.28; 95% confidence interval [CI], 0.20-0.39; P < .001). Although median PFS was not reached in either group, the estimated 24-month PFS was notably higher among those with uMRD (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001).
Furthermore, subgroup analyses underscored the consistency of these findings across different treatment settings. In the first-line treatment setting, achieving uMRD was associated with an HR of 0.24 (95% CI, 0.18-0.33), while in relapsed or refractory CLL, the HR was 0.34 (95% CI, 0.16-0.71). Trials employing time-limited therapy also demonstrated a strong association between uMRD and improved PFS (HR, 0.28; 95% CI, 0.19-0.40).
The implications of these findings are potentially significant for clinical trial design, indicating MRD as an endpoint could potentially enhance the efficiency of CLL trials by providing early insights into treatment efficacy. Moreover, these results may support regulatory decisions to expedite drug approvals based on MRD outcomes. Overall, the systematic review and meta-analysis provide compelling evidence that monitoring MRD status offers valuable prognostic information in CLL, aiding in more precise treatment strategies and potentially improving patient outcomes. Future research is encouraged to validate these findings further and explore additional implications of MRD assessment in clinical practice.
Laith Gergi, EMJ
Reference:
Rios-Olais FA et al. Measurable residual disease and clinical outcomes in chronic lymphocytic leukemia: a systematic review and meta-analysis. JAMA Oncol. 2024;DOI:10.1001/jamaoncol.2024.2122.
