Measurable residual disease status predicts PFS for patients with chronic lymphocytic leukemia
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Key takeaways:
- Patients who achieved undetectable measurable residual disease had a 72% reduced risk for disease progression or death.
- The findings suggest MRD can be a surrogate endpoint for PFS in clinical trials.
Patients with chronic lymphocytic leukemia who achieved undetectable minimal residual disease achieved significantly longer PFS than patients with minimal residual disease, according to results of a systematic review and meta-analysis.
Assessment of minimal residual disease (MRD) status as a clinical trial endpoint — and as a surrogate for PFS — could improve trial efficiency and possibly result in accelerated drug registration, researchers concluded.
“The magnitude of benefit associated with [undetectable] MRD was substantial,” Fausto Alfredo Rios-Olais, MD, of the hematology and oncology department at Instituto Nacional de Ciencias Médicas y Nutrición in Mexico, and colleagues wrote.
The potential for MRD status to serve as a surrogate endpoint in CLL in the era of targeted agents remains unclear, according to study background.
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.
Investigators used PubMed, Embase and other sources to identify prospective single-arm and randomized clinical trials conducted through July 2023 that reported PFS outcomes based on MRD status.
The analysis included 11 prospective trials — two nonrandomized and nine randomized — with a combined 2,765 patients.
Results showed patients who achieved undetectable MRD at a threshold of 0.01% had significantly longer PFS than those who did not reach that threshold (HR = 0.28; 95% CI, 0.2-0.39).
Median PFS had not been reached in either group; however, researchers reported a higher 24-month PFS rate for those who achieved undetectable MRD (91.9% vs. 75.3%; P < .001).
Researchers observed the association between undetectable MRD and PFS in subgroup analyses of patients treated in the first-line setting (HR = 0.24; 95% CI, 0.18-0.33), those treated in the relapsed or refractory disease setting (HR = 0.34; 95% CI, 0.16-0.71), and in trials that used time-limited therapy (HR = 0.28; 95% CI, 0.19-0.4).
Rios-Olais and colleagues acknowledged study limitations. These included heterogeneity of reported effect sizes in the studies analyzed; the fact some trials only measured MRD for patients who achieved complete response to therapy, meaning those who achieved undetectable MRD after partial response were not included; and the fact that the association between MRD and OS remains unclear..
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