Results from AMBER, a randomized phase 2 study of bevacizumab and bortezomib versus bortezomib in relapsed or refractory multiple myeloma.
BACKGROUND
Newer systemic therapies have significantly advanced the treatment of multiple myeloma, but additional agents are needed. Bortezomib is a proteasome inhibitor with efficacy in relapsed/refractory multiple myeloma that inhibits tumor angiogenesis, a process that has been implicated in multiple myeloma pathogenesis.


METHODS
In AMBER("A Randomized, Blinded, Placebo-Controlled, Multicenter, Phase II Study of Bevacizumab in Combination With Bortezomib in Patients With Relapsed or Refractory Multiple Myeloma"), patients with relapsed or refractory multiple myeloma were randomized to receive bortezomib (1.3 mg/m(2) on days 1, 4, 8, and 11 of each 21-day cycle) and either placebo or bevacizumab (15 mg/kg on day 1 of each cycle) for up to 8 cycles. At completion, patients in the bortezomib-plus-bevacizumab arm could continue bevacizumab until they developed progressive disease or unacceptable toxicity. The primary endpoint was progression-free survival (PFS).


RESULTS
The stratified hazard ratio of PFS for the bevacizumab-containing arm (n = 49) relative to the bortezomib monotherapy arm (n = 53) was 0.743 (95% confidence interval [CI], 0.43-1.28; P = .2804); the median PFS was 6.2 months (95% CI, 4.4-8.5 months) and 5.1 months (95% CI, 4.2-7.2 months), respectively; the overall response rates were 51% and 43.4% (P = .4029), respectively; and the median response duration was 6.9 months (95% CI, 4.73-11.83 months) and 6.0 months (95% CI, 4.86-8.31 months), respectively. Frequent adverse events occurred at similar rates across treatment arms, but hypertension, fatigue, and neuralgia occurred more frequently in the bevacizumab-containing arm.


CONCLUSIONS
The addition of bevacizumab to bortezomib in unselected patients with pretreated multiple myeloma did not result in significant improvements in efficacy outcomes. The combination was well tolerated, and no new safety concerns for either agent were identified.
Division of Hematology, Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia, Canada. d.white@dal.ca
Darrell
D
White
Adetola
A
Kassim
Birbal
B
Bhaskar
Jing
J
Yi
Karen
K
Wamstad
Virginia E
VE
Paton
D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016016:Proportional Hazards Models; D011719:Pyrazines / Q000008:administration & dosage; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D001897:Boronic Acids; D011719:Pyrazines; D000068258:Bevacizumab; D000069286:Bortezomib