A Phase I/II National Multicenter Open-label Study
of Bortezomib Plus Melphalan and Prednisone
in Elderly Untreated Multiple Myeloma Patients
M. V. Mateos1, J. Bladé1, J. Diaz Mediavilla1, J. J. Lahuerta1, M. J. Terol,1,
J. Hernández1, M. J. Moro1, J. Bargay1, J. De Larubia1, A. Sureda, J. M.
Ribera1, D. Carrera1, F. de Arriba1, L. Palomera1, M. Hernández1, J. García
Larańa1, A. Alegre1, F. Próper1,
P. Rivas1, D. L. Esseltine2,
D.Schenkein2, J. F. San Miguel 1
1Hematology, Grupo Espańol de MM (GEM/PETHEMA), Spain
2Millennium Pharmaceuticals, Inc., Cambridge, MA, United States
Treatment
ˇ
Four 6-week cycles of intravenous bolus bortezomib, oral
melphalan and oral prednisone followed by up to five 5-week
cycles for a maximum of 49 weeks of treatment
ˇ
Phase 1
­ Cohort 1 (N = 6): bortezomib 1.0 mg/m2
­ Cohort 2 (N = 6): escalate to bortezomib 1.3 mg/m2
ˇ
Phase 2: up to 60 patients in an expanded cohort at the MTD
Treatment schedule
ˇ 6-week cycle
Day
1 2 3 4
8
11
22
25
29
32
33­42
Bortezomib
Rest






Melphalan 9 mg/m2
period
Prednisone 60 mg/m2
ˇ 5-week cycle
Day
1 2 3 4
8
15
22 23­35
Bortezomib



Rest
Melphalan 9 mg/m2
period
Prednisone 60 mg/m2
MOST COMMON ADVERSE EVENTS
GRADE 1-2 (n:12)
PER NEUROPATHY
17
THROMBOCITOPENIA
59
NEUTROPENIA
75
ANEMIA
75
ANOREXIA
33
INFECTION
17
FEVER
25
DIARRHOEA
17
CONSTIPATION
33
RASH
17
VOMITING
41
NAUSEA
66
0
1020
3040
5060
7080
Incidence
Preliminary Efficacy
ˇ 11 patients evaluable
ˇ Mean 4 cycles administered (range 2­6)
ˇ Response during Phase 1: all 11 patients had > 25%
paraprotein response
­ 2 CR (0ne immunofixation negative & one positive)
after 2 cycles of treatment
­ 8 PR: 6 of 8 with > 80% dose reduction in M-protein
concentration
­ 1 MR
Evaluation is ongoing in the Phase 2 portion
Conclusions
ˇ Recommended phase 2 bortezomib dose
­ Bortezomib 1.3 mg/m2
­ Melphalan 9 mg/m2
­ Prednisone 60 mg/m2
ˇ Manageable toxicities
ˇ M-protein responses observed in Phase 1
portion ­ 10/11 evaluable patients had PR

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