Measurable residual disease (MRD) refers to the presence of disease at low levels not detected by conventional pathologic analysis. The association of MRD status as a surrogate end point of clinical outcome in chronic lymphocytic leukemia (CLL) has not been established in the era of targeted agents. Assessing the association of MRD with progression-free survival (PFS) may improve its role as a surrogate marker and allow its use to accelerate drug development.
pubmed.ncbi.nlm.nih.gov/389...
Results: A total of 11 prospective clinical trials (9 randomized and 2 nonrandomized) including 2765 patients were analyzed. Achieving undetectable MRD (uMRD) at 0.01% was associated with an HR of 0.28 (95% CI, 0.20-0.39; P < .001) for PFS. Median PFS was not reached in both groups (uMRD vs MRD), but the estimated 24-month PFS was better in the uMRD group (91.9% [95% CI, 88.8%-95.2%] vs 75.3% [95% CI, 64.7%-87.6%]; P < .001). The association of uMRD with PFS was observed in subgroup analyses in the first-line treatment setting (HR, 0.24; 95% CI, 0.18-0.33), relapsed or refractory disease setting (HR, 0.34; 95% CI, 0.16-0.71), and trials using time-limited therapy (HR, 0.28; 95% CI, 0.19-0.40).
Conclusions and relevance: The findings of this systematic review and meta-analysis suggest that assessing MRD status as an end point in clinical trials and as a surrogate of PFS may improve trial efficiency and potentially allow for accelerated drug registration.
The results from this meta-analysis of nearly 3,000 patients treated for their CLL with targeted therapies, are covered in this Healio News item;
Measurable residual disease status predicts PFS for patients with chronic lymphocytic leukemia
healio.com/news/hematology-...
Rios-Olais and colleagues used data from prospective trials that evaluated targeted agents or obinutuzumab (Gazyva, Genentech)-based treatment to evaluate the association between MRD and PFS for patients with CLL.
Key takeaways:
- Patients who achieved undetectable measurable residual disease (uMRD) had a 72% reduced risk for disease progression or death.
- The findings suggest MRD can be a surrogate endpoint for PFS in clinical trials.
As a result of this meta-analysis, expect more treatment protocols that extend treatment time or add additional targeted therapies or incorporate a combination of these, to increase the percentage of patients achieving uMRD and hence longer drug holidays. Longer remissions should also extend life expectancy, as there will be less risk of running out of treatment options.
Neil