Abstract
For risk‐adaptive therapeutic approaches in multiple myeloma (MM) treatment, we analyzed treatment outcome according to in situ hybridization (FISH) profiles to investigate the prognostic and predictive values of structural variations in a large series of Asian population. A total of 565 newly diagnosed patients with multiple myeloma between January 2005 and June 2015 were evaluated. FISH results showed del(17p13) in 8.8% (29/331), del(13q14) in 35.5% (184/519), t(14;16) in 2.5% (8/326), t(4;14) in 27.9% (109/390), IgH rearrangement in 47.7% (248/520), and +1q21 in 40.8% (211/517). The presence of del(17p13), IgH rearrangement, and t(14;16) was associated with worse overall survival. Interestingly, however, the presence of t(4;14) conferred little prognostic impact. Treatment‐specific analysis revealed the presence of del(17p13), t(14;16), IgH rearrangement, and trisomy 1q21 was predictive of unsatisfactory response to bortezomib. On the other hand, patients with del(13q14) and del(9p21) were less likely to benefit from lenalidomide. Autologous stem cell transplantation (autoSCT) was less effective in patients with del(17p13), t(14;16), and trisomy 1q21. Predictive values of del(17p13) and t(14;16) to bortezomib and autoSCT are seemingly universal, but predictive marker del(13q14) and del(9p21) for lenalidomide response appears ethnicity‐specific. Thus, FISH profiles in MM treatment should be interpreted with regards to patient's ethnicity.
Highlights
Multiple myeloma (MM) represents a considerable clinical challenge as both the number of patients [1] and the treatment cost have been rising [2,3,4]
The International Myeloma Working Group and the Mayo group established a consensus that FISH testing for t(4;14), t(14;16), and del(17p13) should be carried out for all patients to identity high-risk disease [6, 9, 13]
Bortezomib-based induction was used in 46 patients (19.1%), and none received lenalidomide as induction for Autologous stem cell transplantation (autoSCT) (Table 1 and Fig. 1)
Summary
Multiple myeloma (MM) represents a considerable clinical challenge as both the number of patients [1] and the treatment cost have been rising [2,3,4]. In attempts to identify predictive and prognostic markers for MM, various groups have proposed different risk stratification methodologies based on molecular, cytogenetic, and clinical data (https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf) [6, 9,10,11,12,13]. The International Myeloma Working Group and the Mayo group established a consensus that FISH testing for t(4;14), t(14;16), and del(17p13) should be carried out for all patients to identity high-risk disease [6, 9, 13]. The Medical Research Council Myeloma IX trial suggested performing additional FISH analysis for trisomy 1q and t(14;20) to further aid in risk stratification [10] and current NCCN guideline recommends FISH testing for deletion 13, del(17p13), t(4;14), t(11;14), t(14;16), and trisomy 1q21 (https://www.nccn.org/professionals/physician_gls/pdf/ myeloma.pdf). The prognostic predictive value of each chromosomal aberration by FISH varies per reporting group; large-scale data analysis is imperative to accurately explore the impact of specific FISH abnormality
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