RESUMEN
The Revised International Staging System (R-ISS) stratifies patients affected by Multiple Myeloma (MM) into three distinct risk groups: R-ISS I [ISS Stage I, Standard-Risk cytogenetics and normal Lactase DeHydrogenase (LDH)], R-ISS III (ISS stage III and either high-risk cytogenetics or high LDH) and R-ISS II (any other characteristics). With the aim to verify whether the three R-ISS groups could be divided into subgroups with different prognostic factors based on the detection of Circulating Plasma Cells (CPCs) at diagnosis, in this retrospective analysis, we evaluated 161 patients with MM treated at our centre between 2005 and 2017. In all, 57 patients (33·9%) were staged as R-ISS III, 98 (58·3%) as R-ISS II and six (3·6%) as R-ISS I. CPCs were detected in 125 patients (74·4%), while in 43 patients (25·6%) no CPCs were seen. Our analysis revealed that Overall Survival (OS) and progression-free survival (PFS) rates in R-ISS II patients were higher in the subgroup without CPCs compared to the subgroup with ≥1 CPCs (OS: 44·7% vs. 16·3%, P = 0·0089; PFS: 27·8% vs. 8·1%, P = 0·0118). Our present findings suggest that the detection of CPCs at diagnosis may be used as a further prognostic biomarker to improve the risk stratification of patients with MM staged as R-ISS II.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple , Células Neoplásicas Circulantes/metabolismo , Células Plasmáticas/metabolismo , Trasplante de Células Madre , Adulto , Anciano , Anciano de 80 o más Años , Autoinjertos , Dexametasona/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Factores Inmunológicos/administración & dosificación , Masculino , Persona de Mediana Edad , Mieloma Múltiple/sangre , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/terapia , Estadificación de Neoplasias , Inhibidores de Proteasoma/administración & dosificación , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
The mutational status of the IGHV gene is routinely assessed in patients with chronic lymphocytic leukaemia (CLL), since it is both prognostic of clinical outcome and predictive of response to treatment. This study evaluates the IGHV mutational status, assessed in newly diagnosed CLL patients, as a stand-alone predictor of time to first treatment (TTFT). We analysed the data of 236 CLL patients, diagnosed at our centre between January 2004 and September 2020, with a minimum follow-up period of 3.0 years, Binet A-B and Rai 0-II stages. IGHV was unmutated in 38.1â¯% and mutated in 61.9â¯% of cases. The univariate analysis showed a statistically significant difference (p < 0.001) in TTFT based on unmutated (85.2â¯% at 14 years, 95â¯% CI = 63.3-94.5â¯%) or mutated (41.3â¯% at 14 years, 95â¯% CI = 29.5-51.8â¯%) and the need for treatment at 1, 3 and 5 years was of 20.0â¯% vs 4.1â¯% (p < 0.001), 42.7â¯% vs 11.4â¯% (p < 0.001) and 55.8â¯% vs 20.0â¯% (p < 0.001) in unmutated and mutated IGHV patients, respectively. Multivariate analysis confirmed that unmutated IGHV status negatively affects TTFT (p < 0.001), in addition to high-risk genomic aberration (p = 0.025), Rai stage I (p = 0.007) and II (p-valueâ¯<â¯0.001). The difference in TTFT based on unmutated or mutated IGHV status remains statistically significant also when considering the subgroups by the genomic aberrations and Rai stages. Our findings suggest that, with the single analysis of the IGHV mutational status at CLL diagnosis, along with clinical and laboratory data, and without karyotype and TP53 data, clinicians will have prognostic and predictive indications for the first clinical treatment and appropriate follow-up of patients.