Distinct predictive impact of FISH abnormality in
proteasome inhibitors and immunomodulatory agents
response: redeﬁning high- risk multiple myeloma in Asian
Ja Min Byun
, Dong-Yeop Shin
, Junshik Hong
, Inho Kim
, Hyun Kyung Kim
Dong Soon Lee
, Youngil Koh
* & Sung-Soo Yoon
Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Korea
Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
Cancer Research Institute, Seoul National University Hospital, Seoul, Korea
Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea
© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use,
distribution and reproduction in any medium, provided the original work is properly cited.
Asian, immunomodulatory drugs, in situ
hybridization, multiple myeloma, proteasome
Youngil Koh or Sung-Soo Yoon, Department
of Internal Medicine, Seoul National
University Hospital, 101, Daehak-ro,
Jongro-gu, Seoul 03080, Korea.
Tel: +82-2-2072-2228 (YK);
Tel: +82-2-2072-3079 (S-SY);
E-mails: email@example.com (YK);
This research was supported by a grant of the
Korea Health Technology R&D Project
through the Korea Health Industry
Development Institute (KHIDI), funded by the
Ministry of Health & Welfare, Republic of
Korea (grant number: HC15C3397).
Received: 12 September 2017; Revised: 27
November 2017; Accepted: 21 December
Cancer Medicine 2018; 7(3):831–841
*These authors contributed equally to this
work and are cocorrespondence to this work.
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.