Expression of Intergrin Beta 7 (IT7) Identify a High Risk Group among Multiple Myeloma (MM) Patients (Pts) Treated with High Dose Chemotherapy Followed by Autologus Stem Cell Transplantation (ASCT)
A Mansoor, SMT Rad, A Klimowicz, A Magliocco, X Jiang, D Stewart, N Bahlis. University of Calgary/CLS, Calgary, AB, Canada; Tom Baker Cancer Ctr., Calgary, AB, Canada
Background: Gene expression profile (GEP) identified various prognostic sub-groups (e.g. c-MAF, MAFB-, MMSET etc) in MM pts. c-MAF translocated in (10%) MM pts, stimulate cell cycle progression and promote stromal interactions through Cyclin D2, IT7, & CCR1 as target genes. In MM, IT7 is also up-regulated through other pathways and enhances production of VEGF. Since, GEP has limited applicability (complex methodology & high cost); we evaluated expression of cyclin D2 and IT7 by immunohisto-chemistry (IHC) in a cohort of MM pts and correlated our results with clinical progression.
Design: Diagnostic BM biopsy tissue (FFPE) of MM pts (treated with a dexamethasone based regimen & ASCT) were stained with CD138; CD45, CD20; ,, cyclin D2 and IT 7 antibodies; using standardized techniques & appropriate controls. Two pathologists (blinded to clinical outcome), scored staining as positive (>50% MM cells, irrespective of intensity) or negative. FISH studies for del 13; t(4;14) & del 17p were performed. The clinical parameters, response criteria and survival outcomes (PFS and OS) were defined according to the international uniform response criteria. OS [amp time to progress (TTP) was determined by Kaplan-Meier method. Cox regression method was used for multivariate analysis.
Results: 79 pts between 27-72 yrs of age ((median 54.4) were included. 17.7% had ISS stage III, median 2-microglobulin was 3.29 mg/L (1.1637.05). Del13q, t(4;14) and del17p13 were detected in 35.9%, 13.6% and 17.3%, respectively. Post ASCT, 68.8% achieved a CR or VGPR with mTTP of 2.3 yrs (C.I. 1.8-2.7) and mOS of 8.1 yrs (C.I. 5.3-10.7 ). Expression of cyclin D2 was seen in 76.6% cases while integrin-7 was noted among 17.7% of samples. In univariate analysis integrin-7 predicted for a shorter TTP(mTTP 0.9 vs 2.4 yrs, P=0.008) but not OS (P=0.570), whereas the expression of cyclin D2, did not affect TTP or OS. In multivariate analysis (age, -2 microglobulin, del13q, integrin 7 and cyclin D2) presence of del13 or integrin 7 were the only independent predictors of TTP with HR of 3.892 and 4.029 respectively.
Conclusions: Detection of IT7 expression by a routinely applicable methodology, identify a high risk group in MM pts. These pts can be spared of toxicities of ASCT through offering of upfront novel therapeutic agents.
Monday, March 9, 2009 2:15 PM
Platform Session: Section D, Monday Afternoon