Digital PCR (dPCR) is able to anticipate the achievement of stable deep molecular response in adult chronic myeloid leukemia patients: results of the DEMONSTRATE study

Simona Bernardi ^1,2,3, Alessia Cavalleri ^4,5, Silvia Mutti ^4,5

¹Department of Clinical and Experimental Sciences, University of Brescia - Unit of Blood Disease and Stem Cell Transplantation, ASST-Spedali Civili, Brescia, Italy. simona.bernardi@unibs.it.
²Laboratorio CREA (Centro di Ricerca Emato-Oncologica AIL), ASST-Spedali Civili, Brescia, Italy. simona.bernardi@unibs.it.
³National Center for Gene Therapy and Drugs based on RNA Technology - CN3, Padua, Italy. simona.bernardi@unibs.it.
⁴Department of Clinical and Experimental Sciences, University of Brescia - Unit of Blood Disease and Stem Cell Transplantation, ASST-Spedali Civili, Brescia, Italy.
⁵Laboratorio CREA (Centro di Ricerca Emato-Oncologica AIL), ASST-Spedali Civili, Brescia, Italy.
⁶Hematology Division, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
⁷Division of Hematology and BMT, Department of Medical and Morphological Research, University of Udine, Udine, Italy.
⁸Department of Engineering for Innovation Medicine, Section of Innovation Biomedicine, Hematology Area, University of Verona - Department of Medicine, Policlinico G.B.Rossi - AOUI Verona, Verona, Italy.
⁹Hematology and Clinical Immunology, Department of Medicine, Padua School of Medicine, Padua, Italy.

⁰Department of Clinical and Experimental Sciences, University of Brescia - Unit of Blood Disease and Stem Cell Transplantation, ASST-Spedali Civili, Brescia, Italy. simona.bernardi@unibs.it.

Annals of Hematology +

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November 29, 2024

View abstract on PubMed

Summary

Digital PCR (dPCR) offers a more sensitive method for monitoring Minimal Residual Disease (MRD) in Chronic Myeloid Leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI), potentially improving treatment decisions.

Area Of Science

Hematology
Molecular Biology
Oncology

Background

Chronic Myeloid Leukemia (CML) is characterized by the BCR::ABL1 fusion gene.
Monitoring treatment response to tyrosine kinase inhibitors (TKI) is critical for CML management.
Reverse Transcription quantitative PCR (RT-qPCR) has limitations in sensitivity and accuracy for detecting minimal residual disease (MRD).

Purpose Of The Study

To evaluate the efficacy of digital PCR (dPCR) in detecting MRD in CML patients undergoing TKI therapy.
To compare dPCR with RT-qPCR for assessing Deep Molecular Response (DMR) achievement and stability.
To explore dPCR's potential in identifying candidates for treatment-free remission (TFR).

Main Methods

A comparative study involving 79 CML patients (NP 3809 clinical trial) using both dPCR and RT-qPCR.
Assessment of DMR achievement and stability over a 2-year period post-initial DMR.
Statistical analyses including chi-squared tests, Fisher's exact tests, and Kaplan-Meier analysis.

Main Results

dPCR anticipated or coincided DMR achievement in 69/79 patients compared to RT-qPCR.
dPCR showed a statistically significant capability to anticipate (p=0.0012) and coincide (p=0.0017) stable DMR.
No influence of transcript type or TKI choice on DMR achievement or stability was observed with either method.

Conclusions

dPCR is a sensitive and accurate tool for monitoring MRD in CML patients.
dPCR provides valuable information for TKI therapy management and TFR candidate selection.
Standardization of dPCR methods is recommended for broader clinical adoption.

Keywords:

CML MRD TKIs Transcript type dPCR