Microsoft Word - 743 Avet Loiseau Impact of FISH and Cytogenetics On Overall and Event Free Survival in Myeloma

743 Impact of FISH and Cytogenetics On Overall and Event Free Survival in Myeloma: An
IMWG Analysis of 9,897 Patients
Oral and Poster Abstracts
Oral Session: Myeloma - Biology and Pathophysiology, excluding Therapy: Microenvironmental Cell in Multiple
Myeloma and Long-term Follow-up of Patients with Myeloma
Monday, December 7, 2009: 5:30 PM
La Nouvelle Ballroom C (Ernest N. Morial Convention Center)
Herve Avet-Loiseau1*, Brian G M Durie2, Jeff Haessler, MD3*, John Crowley, PhD3, Antje Hoering, Ph.D.3*, Bart
Barlogie, MD, PhD4, John D Shaughnessy Jr.4, Orhan Sezer5*, Chaim Shustik, MD6, Roman Hajek, MD7, Harmut
Goldschmidt8*, Pieter Sonneveld9, Philippe Moreau, MD10*, Michel Attal, MD11, Antonio Palumbo, M.D.12, Mario
Boccadoro, MD13*, Jae Hoon Lee14, Jan Westin, MD, PhD15, Ingemar Turesson, MD, PhD16*, Jesús F. San Miguel17*,
Joan Blade18, Juan José Lahuerta, MD, PhD19*, Santiago Pavlovsky, MD, PhD20, Dorotea Beatriz Fantl, MD21,
S.Vincent Rajkumar, M.D.22* and Rafael Fonseca, MD23
1Institute de Biologie, Nantes, France
2Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA
3Cancer Research & Biostatistics, Seattle, WA
4Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR
5University Hospital Charité, Berlin, Germany
6Royal Victoria Hospital, Montreal, QC, Canada
7Clinic of Internal Medicine Hematology and Oncology, Faculty Hospital Brno, Brno, Czech Republic
8Hematology, Oncology, Rheumatology, University of Heidelberg, Heidelberg, Germany
9Dept. of Hematology, Erasmus MC, Rotterdam, Netherlands
10University Hospital, Nantes, France
11CHU Dept Hematologie, University Hospital, Toulouse, France
12Division of Hematology, University of Turin, Turin, Italy
13Division of Hematology, University of Torino, Torino, Italy
14Gachon University Gil Hospital, Incheon, South Korea
15Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden
16Department of Medicine, Malmo University Hospital, Malmo, Sweden
17Hospital Universitario de Salamanca, Salamanca, Spain
18Hospital Clinic, Barcelona, Spain
19Hospital 12 de Octubre, Madrid, Spain
20Fundaleu, Buenos Aires, Argentina
21Hematologia, Hospital Italiano, Buenos Aires, Argentina
22Hematology, Mayo Clinic, Rochester, MN
23Mayo Clinic Scottsdale, Scottsdale, AZ
Background
There has been considerable recent focus upon the molecular classification of myeloma. However, the prognostic
impact of molecular changes has mostly been assessed from small and/or incomplete studies from single
institutions or groups. There has been no large scale analysis of molecular features linked to ISS stage.
Methods
In order to clarify the overall impact of molecular changes we undertook a collective analysis of 9,897 patients
through the International Myeloma Working Group (IMWG). Within this population 2,295 patients had presence of
cytogenetic abnormalities (Any CA); 1,713 hypodiploidy; 1,673 hyperdiploidy; 2,309 cytogenetic deletion 13;
3,226 deletion 13 by FISH; 1,573 FISH t(4;14); 1,486 FISH del p17; 1, 683 FISH t(11:14); and 366 FISH t(4;16).
Enrolled patients had complete clinical and treatment details available including baseline standard prognostic
factors, ISS stage, as well as both progression free survival (PFS) and overall survival (OS) information. Data
came from 14 sites: 3 from the US and the remainder from Europe, Asia, and Latin America as for the ISS staging
system analyses. Univariate and multivariate analyses were performed.
Results
Each of the known adverse molecular features had a negative impact upon both PFS and OS (p=002 - <0.0001).
Among the deleterious FISH abnormalities the t(4;14) abnormality was the most highly correlated with poorer
outcomes by PFS: 4 year estimate: 32% vs. 60% (p<0.0001). The t(4;14) abnormality combined with ISS Stage

also significantly enhanced predictive capability: ISS Stage I without t(4;14) OS 81% @ 4 years; ISS Stage III
with t(4;14) OS 22% @ 4 years (P<0.0001) [Figure 1]. The best outcomes were for ISS Stage I in the presence
of t(11;14): OS 89% @ 4 years. Absence of any one adverse feature correlated with 80-81% OS @ 4 years for
Stage I. Presence of any one adverse feature had a more variable impact and correlated with 22%-40% OS at 4
years for Stage III.
In univariate correlations the most predictive correlations with OS were presence of Any CA, t(4;14), 17p-,
hypodiploidy, cytogenetic 13q- with R2 values of 6.9%, 4.5%, 4.1% and 3.8% respectively. In multivariate
analyses, ISS stage provided the best predictions: R2 values = 13.3%. The added contributions from molecular
features were: t(4;14) 3.8%; cytogenetic 13q- 2.9%; Any CA 2.3%; and 17p- 1.0%. The maximum total R2 for
OS was 22%.
Conclusions
This large multicenter analysis confirms the correlations between abnormal molecular findings and outcomes.
Combinations with ISS Stage provide the best predictive capability. Presence of Any CA, t(4;14), 17p-,
hypodiploidy and cytogenetic 13q- contribute to poorer outcomes by ISS stage. The presence of hyperdiploidy
and/or t(11;14) contribute to better outcomes. There is thus validation of prior molecular studies related to
prognosis utilizing this large IMWG database.
Figure 1
Overall Survival: With (+) and Without (-) t(4;14)
Disclosures: No relevant conflicts of interest to declare.