Primary therapy with single agent bortezomib as induction, maintenance and re-induction in patients with high-risk myeloma: results of the ECOG E2A02 trial.
Single agent bortezomib results in response rates of 51% in patients with newly diagnosed multiple myeloma and is touted to be especially effective in high-risk disease. We are the first to prospectively explore single agent bortezomib as primary therapy (induction, maintenance and re-induction) without consolidative autologous stem cell transplant in a cohort selected to have high-risk multiple myeloma. Patients received eight cycles of induction, followed by maintenance bortezomib every other week, indefinitely. Patients relapsing on maintenance had the full induction schedule resumed. On an intention-to-treat basis, the response rate (>or=partial response) was 48%. Among seven patients who progressed on maintenance bortezomib and received re-induction, two responded to the treatment. With a median follow-up of 48.2 months, 1- and 2-year overall survival probabilities were 88% (95% confidence interval (CI) 79-98%) and 76% (95% CI 60-86%), respectively. Median progression-free survival was 7.9 months (95% CI 5.8-12.0). Twenty-three and thirty-four patients had >or=grade 3 hematological and non-hematological toxicity, respectively, with treatment-emergent neuropathy in 7% with motor grade 1-2, 56% with sensory grade 1-2 and 2% with grade 3, and in 14% with neuropathic pain grade 1-2 and 2% with grade 3. In high-risk patients, upfront bortezomib results in response rates that are comparable to those reported for unselected cohorts, but single agent bortezomib is not sufficient as primary therapy.
Dispenzieri
A
A
Department of Hematology, Mayo Clinic, Rochester, MN 55905, USA. dispenzieri.angela@mayo.edu
Jacobus
S
S
Vesole
D H
DH
Callandar
N
N
Fonseca
R
R
Greipp
P R
PR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D015331:Cohort Studies; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib