Novel Molecular Technologies

PCR techniques are the gold standard for MRD analysis in patients with lymphomas. International standardization of MRD monitoring has established quantitative PCR as a common method in numerous lymphoma clinical trials. However, this approach is often criticized due to the standard curve required for sample quantification. The process is lengthy and involves specific reagents and markers along with ample amount of the sample to adequately perform measurements.

Several novel molecular techniques are now being used for MRD detection that have overcome some of the challenges associated with conventional methods. The recently introduced droplet digital PCR assay requires no standard curve; therefore, it may enhance disease quantification at diagnosis and ongoing clinical monitoring during follow-up visits. Additionally, next generation sequencing technology has been shown to improve screening and may supplement current standardized PCR detection methods.

Marco Ladetto, MD, of the department of molecular biotechnology and health sciences at the University of Turin in Italy, told Hematology Advisor, “Solid results [have been] seen with newer [PCR technologies] compared with standardized MRD PCR [techniques].”

Limitations of these new molecular techniques include the lack of standardization, which may slow integration into clinical settings.

Moving Forward

Major advances in MRD monitoring may improve evaluation of prognosis in patients with indolent lymphomas. Management strategies for these pathologies are becoming more complex and are increasingly based on the personalized molecular characteristics of each individual. As a result, molecular detection technologies are evolving in a similar manner.

“We [in addition to] others are [continuing to] develop alternative PCR detection tools,” Dr Ladetto concluded.

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References

1. Grimaldi D, Genuardi E, Ferrante M, Ferrero S, Ladetto M. Minimal residual disease in indolent lymphomas: A critical assessment. Curr Treat Options Oncol. 2018;19:71. doi: 10.1007/s11864-018-0594-1

2. Kahl BA-O, Yang DA-O. Follicular lymphoma: evolving therapeutic strategies. Blood. 2016;127:2055-2063. doi: 10.1182/blood-2015-11-624288