Poster Session II: Myeloma and other monoclonal gammopathies - Biology & translational research
Identification of cMYC/8q24 translocations (t(8q24)/cMYC) is not included in routine diagnostic test for multiple myeloma (MM) patients and prognostic significans of cMYC/8q24 rearrangement is not completely clarified.
To define the frequency of t(8q24)/cMYC in MM and their correlation with clinical course and prognosis.
In 134 patients (pts) with newly diagnosed MM from December, 2009 to March, 2017, 67 male and 67 female, median age 57 years (30-81), we performed FISH with locus-specific and centromere DNA probes (XL 1p32/1q21, XL IGH plus, XL t(11;14), XL t(4;14), XL t(14;16), XL t(14;20), XL t(6;14), XL cMYC BA, XL 5p15/9q22/15q22, XL P53 (MetaSystems), D13S25 (Cytocell). Induction therapy with bortezomib-based courses was initiated for 131 pts, 3 pts with smoldering MM remained under observation. Response was evaluated according to the IMWG criteria (2014, 2016) for 127 pts, because 4 pts died in induction. 50 pts were underwent ASCT. The median follow-up of group was 20 months (3,2 - 77,4).
Chromosomal aberrations were revealed in 133 of 134 (99.3%) pts. Primary genetic events were detected in 88.8%: t(14q32)/IGH - in 42.5% (57/134), hyperdiploidy in - 57.5% (77/134), in 11.2% (15/134) a concurrent t(14q32)/IGH and a hyperdiploidy were found. In 11.2% primary genetic events were not found. The IGH translocations t(11;14), t(4;14), t(14;16), t(14;20), t(6;14) were observed at a frequency of 16.4%, 12.7%, 3.7%, 2.2%, 0.7% respectively, chromosomal partner is not found in 6.8%. Secondary genetic events were detected in 69.4%: del13q/-13 - in 40.3% (54/134), amp1q21 - in 39.6% (53/134), t(8q24)/cMYC - in 17.2% (23/134), del(17p) - in 12.7% (17/134), del1p32 - in 2.2% (3/134), amp(8q24)/cMYC - in 0.7% (1/134). Cases with t(8q24)/cMYC correlated with higher b2-microglobulin levels (more 5,5 mg/L) (OR = 3.28 (1.20-8.94); p = 0.016) and accordingly III stage by ISS (p = 0.045).
The difference in response after induction in pts with or without t(8q24)/cMYC was statistically significant: overall response (OR) - 40.9% versus 84.8%; bortezomib-based therapy resistance 59.1% versus 15,2% (p <.0001) (Figure 1a). Pts with t(8q24)/cMYC had significantly worse 3-year overall survival (OS) (50.8% vs 67%; p = 0.001) (Figure 1b). On multivariate analysis t(8q24)/cMYC (HR = 4.5, p = 0.0013), del(17p) (HR = 4.5, p = 0.0004) and amp1q21 with > 3 copies of locus 1q21 (HR = 1.8, p = 0.0014) were found to be an independent adverse predictors of shorter OS. ASCT improves survival rates of OS, but does not nil the negative impact of t(8q24)/cMYC, del(17p) and > 3 copies of 1q21.
Our results show that t(8q24)/cMYC have significant impact on MM. The presence t(8q24)/cMYC is associated with resistance to bortezomib-based therapy and low OS MM pts.