Professor MD Anderson Cancer Center, Texas, United States
Introduction: Risk stratification in multiple myeloma (MM) patients remains challenging despite the currently available models. TP53 deletion/monosomy 17 detected by conventional cytogenetics and fluorescence in situ hybridization (FISH) is commonly regarded as an adverse risk factor. However, the clinicopathologic features of MM patients with TP53 mutations detected by sequencing and the prognostic impact of these mutations have not been well studied. We summarize the clinicopathologic features of 73 patients with TP53 mutated MM.
Methods: We searched our institutional database for patients with TP53 mutated MM. The clinicopathologic and laboratory data were collected from the medical record. A separate group of 61 TP53 wild type MM patients served as control. TP53 mutations were detected and analyzed by next generation sequencing (NGS).
Results: The 73 study cohort patients had a median age of 64 years (range, 36-94 yrs). TP53 was the sole mutation detected in MM in 44 (60.2%) patients. The most common co-occurring mutations detected in MM included KRAS (n=16, 21.9%) and NRAS (n=12, 16.4%). The most common co-occurring cytogenetic aberrations included RB1 deletion (n=67, 91.8%), CKS1B gain (n=58, 79.4%), TP53 deletion/monosomy 17 (n=38, 52%) and CCND1::IGH fusion (n=35, 47.9%). TP53 mutated MM patients had more advanced R-ISS stage and a shorter overall survival compared with TP53 wild type MM patients (p=0.006 and p=0.02 respectively).
Conclusions: TP53 mutations in MM are associated with a higher R-ISS stage, are frequently associated with CKS1B gains and affected patients have shorter overall survival. Our data confirm that TP53 mutations carry adverse prognostic significance, similar to TP53 deletion/monosomy 17, and need to be incorporated into risk assessment and treatment planning of MM patients.
