Phase 2 Trial of Single Agent
Bortezomib in Patients with
Previously Untreated Multiple
Myeloma (MM)
Paul G. Richardson1, Asher Chanan-Khan2, Robert Schlossman1, Nikhil Munshi1, Patrick Wen*1, Hannah
Briemberg*1, David Kuter3, Anne-Louise Oaklander*3, Sagar Lonial4, Hani Hassoun5, Deborah Doss*1,
Kathleen Colson*1, Mary McKenney*1, Karen Hande*1, Alexandra Koryzna*2,Barbara Stoklas*3, Laura
Lunde*1, Svetlana Gorelik*1, Cliona McAlister*1, Andrea Freeman*1, Diane Warren*1, Denise Collins*6,
Dixie Esseltine6, Anthony Amato*1, Kenneth C. Anderson1
1Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and Brigham and Women's
Hospital, 2Roswell Park Cancer Institute, 3Massachusetts General Hospital, 4Emory University,
5Memorial-Sloan Kettering Cancer Center 6Millennium Pharmaceuticals Inc.
Single-Agent Bortezomib as Front-line
Therapy for untreated MM
· Pt Population
Newly diagnosed pts with MM
· Planned accrual
48 pts
· Objectives
Primary:
- ORR (CR+PR)
Secondary:
- TTP
- Incidence, Characterization of PN,
Effect of Interventions
- Pharmacogenomics
Study Schema
Long-term
Cycles 1-8
Follow-up
valE
10-d rest
Neuro
End of
Registration
D 1
D 4
D 8
D 11
Treatment visit
· Response assessed by paraprotein and Blade criteria
· CR continue 2 cycles after confirmation
· Neuro evaluation and skin biopsy on development of PN
· Discontinue for PD or toxicity
Centers: DFCI, MGH, BIDMC, Roswell Park, Emory, MSKCC
Bortezomib dose 1.3 mg/m2
Conclusions
· Single agent bortezomib is active in newly diagnosed
pts with MM
­ RR (CR + PR): 45%
­ 67% including MR
­ PD in 7%
· Well tolerated
­ No significant unexpected adverse events (except
testicular swelling)
­ VSV noted prior to prophylaxis with acyclovir
­ Safety profile similar to previous studies
Conclusions (continued)
· Incidence of subclinical PN at baseline: 75%
­ Primarily small fiber
· Treatment-emergent PN: 24% (1 pt G3)
­ Improved in 3 pts with dose reduction or after
completion of therapy
­ Interventions feasible, well tolerated
­ Autonomic dysfunction appears minimal
­ Analysis of skin biopsies ongoing
Future Directions
· Complete current study
­ Expand to N = 60
· Further evaluation of PN
­ Complete neurological evaluations and serial skin
biopsies
­ Correlation of baseline characteristics with outcome
­ Analysis of interventions
­ Assessment of reversibility
· Analysis of PGx
­ Samples collected from all pts to date

Document Outline