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PROGNOSTIC IMPACT OF T(8Q24)/CMYC IN MULTIPLE MYELOMA

PS1353

Abramova, T.1; Obukhova, T.1; Mendeleeva, L.1; Gribanova, E.1; Nakastoev, I.1; Grachev, A.1; Danilina, A.1; Solovev, M.1; Firsova, M.1; Kulikov, S.1; Gal'tseva, I.1; Grebenyuk, L.1; Savchenko, V.1

doi: 10.1097/01.HS9.0000563692.22721.b8
Poster Session II: Myeloma and other monoclonal gammopathies - Biology & translational research
Free

1National Research Center for Hematology, Moscow, Russian Federation

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Background:

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.

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Aims:

To define the frequency of t(8q24)/cMYC in MM and their correlation with clinical course and prognosis.

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Methods:

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).

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Results:

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.

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Summary/Conclusion:

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.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.