Proliferation to Apoptosis Tumor Cell Ratio as a Biomarker to Improve Clinical Management of Pre-Malignant and Symptomatic Plasma Cell Neoplasms

• Main Authors: María A. Vasco-Mogorrón, José A. Campillo, Adela Periago, Valentin Cabañas, Mercedes Berenguer, María C. García-Garay, Lourdes Gimeno, María F. Soto-Ramírez, María D. Martínez-Hernández, Manuel Muro, Alfredo Minguela
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: International Journal of Molecular Sciences
• Subjects: plasma cell neoplasm; MGUS; SMM; MM; treatment; proliferation
• Online Access: https://www.mdpi.com/1422-0067/22/8/3895
• ISSN: 1661-6596; 1422-0067

Proliferation and apoptosis of neoplastic cells are prognostic biomarkers in plasma cell neoplasms (PCNs). The prognostic capacity of proliferation to apoptosis ratio (Ratio-PA) in the era of immunomodulatory treatments is re-evaluated in 316 gammopathy of undetermined significance (MGUS), 57 smoldering multiple myeloma (SMM), and 266 multiple myeloma (MM) patients. Ratio-PA of 0.77 ± 0.12, 1.94 ± 0.52, and 11.2 ± 0.7 (<i>p</i> < 0.0001) were observed in MGUS, SMM, and MM patients. Ten-year overall survival (10y-OS) rates for patients with low/high Ratio-PA were 93.5%/77.3% <i>p</i> < 0.0001) for MGUS, 82.5%/64.7% (<i>p</i> < 0.05) for SMM, and 62.3%/47.0% (<i>p</i> < 0.05) for MM. For patients with low, intermediate, and high risk, 10y-OS for low/high Ratio-PA were 95.5%/72.9% (<i>p</i> < 0.0001), 74.2%/50.4% (<i>p</i> < 0.0001), and 35.3%/20.0% (<i>p</i> = 0.836), respectively. Ratio-PA was an independent prognostic factor for OS (HR = 2.119, <i>p</i> < 0.0001, Harrell-C-statistic = 0.7440 ± 0.0194) when co-analyzed with sex, age, and standard risk. In patients with Ratio-PA^high, only first-line therapy with VRd/VTd, but not PAD/VCD, coupled with ASCT was associated with high 10y-OS (82.7%). Tumor cell Ratio-PA estimated at diagnosis offers a prognostic biomarker that complements standard risk stratification and helps to guide the clinical management of pre-malignant and symptomatic PCNs. Every effort should be made to provide first-line therapies including VTd or VRd associated with ASCT to patients with Ratio-PA^high at higher risk of progression and death.