MRD Positivity Associated With Worse PFS, OS Post-Induction, Consolidation in Patients With MCL

Results from a meta-analysis published in the Journal of Cancer suggested that following induction and consolidation treatments, minimal residual disease (MRD) positivity was associated with worse progression-free survival (PFS) and overall survival (OS) for patients with mantle cell lymphoma (MCL).

Based on these findings, the investigators recommended that MRD-based treatment strategies should continue to be explored in clinical trials and within real-world practice.

“MRD status after both induction therapy and consolidation therapy showed prognostic value,” wrote the study authors, who were led by Yu Zhou. “This may provide information for deciding timing of MRD assessment.”

For the purposes of this study, investigators searched various databases— including Pubmed, Embase, Web of Science, and the Cochrane Library—to extract and analyze patient characteristics, MRD assessment, and survival outcomes. Overall, 10 articles were included in the current assessment.

Ultimately, when compared with MRD-negative status, MRD-positive status was associated with worse PFS (HR, 1.44; 95% CI, 1.27-1.62; P <.00001) and OS (HR, 1.30; 95% CI, 1.03-1.64; P = .03) post-induction. Moreover, MRD positivity also predicted shorter PFS (HR, 1.84; 95% CI, 1.49-2.26; P <.00001) and OS (HR, 2.38; 95% CI, 1.85-3.06; P <.00001) compared to MRD negativity following consolidation.

Though this meta-analysis deemed MRD status to be of prognostic value, the investigators indicated that the recommendation of clinical application of MRD—especially MRD-driven treatment decision—still needs to be confirmed in large prospective cohort studies.

Notably, there is currently an ongoing, prospective, randomized phase 3 study which is evaluating the impact of treatment options on survival outcomes in patients with MCL who are MRD negative (NCT03267433). In this study, patients with MCL who are in MRD-negative first remission will be randomized to undergo autologous hematopoietic stem cell transplantation (auto-HCT) followed by rituximab (Rituxan) maintenance therapy or rituximab maintenance alone (without auto-HCT).

“This study will provide more information on the prognostic value of MRD status in [patients with MCL] and the clinical efficacy of consolidation and maintenance treatment for patients with different post-induction MRD status,” the authors noted.

Importantly, this study did not assess the survival results of different detection methods, given that all included studies used polymerase chain reaction (PCR) as their detection method. Multiparameter flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR) are currently the methods of choice for MRD detection; however, the lower sensitivity of MFC limited its use in the follow-up period compared with PCR. Moreover, RQ-PCR is a sensitive tool for detecting MRD in the follow-up period based on IGH rearrangement, according to the investigators. However, for patients without canonical translocations, the allele-specific oligonucleotide primer design is required, and the current procedure limited the applicability.

“Based on the results mentioned above, we suggest that when applying MRD assessment in clinical practice, the methods for MRD detection should be determined to specific circumstances and should follow standardized protocols,” explained the authors.

In addition, analysis according to other variables were not performed because of the small number of studies available in each subgroup. Due to a lack of individual-level data, the pooled survival rates at certain time points were estimated and investigators could not draw strong conclusions regarding survival probabilities.

Reference:

Zhou Y, Chen H, Tao Y, Zhong Q, Shi Y. Minimal residual disease and survival outcomes in patients with mantle cell lymphoma: a systematic review and meta-analysis. J Cancer. 2021; 12(2):553-561. doi:10.7150/jca.51959