Bortezomib or high-dose dexamethasone for relapsed multiple myeloma.
BACKGROUND
This study compared bortezomib with high-dose dexamethasone in patients with relapsed multiple myeloma who had received one to three previous therapies.


METHODS
We randomly assigned 669 patients with relapsed myeloma to receive either an intravenous bolus of bortezomib (1.3 mg per square meter of body-surface area) on days 1, 4, 8, and 11 for eight three-week cycles, followed by treatment on days 1, 8, 15, and 22 for three five-week cycles, or high-dose dexamethasone (40 mg orally) on days 1 through 4, 9 through 12, and 17 through 20 for four five-week cycles, followed by treatment on days 1 through 4 for five four-week cycles. Patients who were assigned to receive dexamethasone were permitted to cross over to receive bortezomib in a companion study after disease progression.


RESULTS
Patients treated with bortezomib had higher response rates, a longer time to progression (the primary end point), and a longer survival than patients treated with dexamethasone. The combined complete and partial response rates were 38 percent for bortezomib and 18 percent for dexamethasone (P<0.001), and the complete response rates were 6 percent and less than 1 percent, respectively (P<0.001). Median times to progression in the bortezomib and dexamethasone groups were 6.22 months (189 days) and 3.49 months (106 days), respectively (hazard ratio, 0.55; P<0.001). The one-year survival rate was 80 percent among patients taking bortezomib and 66 percent among patients taking dexamethasone (P=0.003), and the hazard ratio for overall survival with bortezomib was 0.57 (P=0.001). Grade 3 or 4 adverse events were reported in 75 percent of patients treated with bortezomib and in 60 percent of those treated with dexamethasone.


CONCLUSIONS
Bortezomib is superior to high-dose dexamethasone for the treatment of patients with multiple myeloma who have had a relapse after one to three previous therapies.
Richardson
Paul G
PG
Dana-Farber Cancer Institute, Boston, MA 02115, USA. paul_richardson@dfci.harvard.edu
Sonneveld
Pieter
P
Schuster
Michael W
MW
Irwin
David
D
Stadtmauer
Edward A
EA
Facon
Thierry
T
Harousseau
Jean-Luc
JL
Ben-Yehuda
Dina
D
Lonial
Sagar
S
Goldschmidt
Hartmut
H
Reece
Donna
D
San-Miguel
Jesus F
JF
Bladé
Joan
J
Boccadoro
Mario
M
Cavenagh
Jamie
J
Dalton
William S
WS
Boral
Anthony L
AL
Esseltine
Dixie L
DL
Porter
Jane B
JB
Schenkein
David
D
Anderson
Kenneth C
KC
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D010976:Platelet Count; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D012008:Recurrence; D015996:Survival Rate
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone