JMIR Publications

ABSTRACT

Background:

Multiple myeloma (MM) is often associated with kidney deficiency, phlegm, and blood stasis, and the method of tonifying the kidney, resolving phlegm, and removing blood stasis is a fundamental therapeutic approach for MM. Emerging evidence implicates the PHD Finger Protein 19 (PHF19)/ Enhancer of Zeste Homolog 2 (EZH2)/ trimethylated histone H3 at lysine 27 (H3K27me3) epigenetic axis in immune microenvironment dysregulation and MM progression. We designed a randomized controlled trial (RCT) to investigate the mechanism and safety of the kidney-tonifying, phlegm-resolving, and blood-stasis-removing(KPR) method in MM.

Objective:

This RCT tests whether a KPR herbal formula combined with standard bortezomib-based therapy improves the immune microenvironment via the PHF19-EZH2-H3K27me3 epigenetic axis to restore immune function in multiple myeloma, providing a mechanistic basis for integrating Traditional Chinese Medicine into evidence-based oncology care of relapsed/refractory patients.

Methods:

This is a single-center, prospective, randomized controlled trial involving patients with MM. Patients will be randomly assigned to three groups (blank control group, western medicine control group, and integrated traditional Chinese and western medicine treatment group) in a 1:1:1 ratio. All participants will receive a 12-week treatment regimen, including oral administration of traditional Chinese medicine(TCM) (the KPR formula or placebo) combined with western medicine therapy (bortezomib/lenalidomide/dexamethasone regimen), followed by a 6-month follow-up assessment. The primary outcome is the CD3⁺ T-cell ratio in bone marrow/peripheral blood, detected using methods such as flow cytometry. Secondary outcomes include quantified TCM syndrome scores, western medical efficacy evaluation criteria, complete blood count, bone marrow morphology, blood and urine immunoglobulins, quantitative M protein, free light chains (FLCs), β2-microglobulin(β2-MG), and whole-body imaging (X-ray, CT, MRI, or PET-CT). Using the CD3+ T cell ratio as the observed outcome indicator, the CD3+ T cell ratio in the western medicine control group is 50.15±4.27. It is estimated that the CD3+ T cell ratio in the integrated treatment group could increase by 3.86 points. With a two-tailed α=0.05 and power of 90%, the required sample size per group is 26 cases. Considering a 1:1:1 randomization, 26 cases are needed per group. Accounting for a 15% loss to follow-up and refusal, a minimum of 31 cases per group (total ≥93 cases) will be enrolled.

Results:

This protocol outlines a study with no results available yet. The recruitment of volunteers began in March 2025, and the project ended in February 2026. Results will be published in a subsequent outcomes paper.

Conclusions:

This first mechanistic RCT evaluating a TCM formula targeting the PHF19-EZH2-H3K27me3 axis in MM will establish a biomarker-driven framework for integrating TCM with immunotherapy, offering novel strategies for treatment-refractory patients. Clinical Trial: International Traditional Medicine Clinical Trial Registry. ITMCTR2025000671 and ITMCTR2025000449. https://itmctr.ccebtcm.org.cn/mgt/project/view/4375050683463103813[1], https://itmctr.ccebtcm.org.cn/mgt/project/view/4779140633660123982.[2]