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 (MM) and is touted to be especially effective in high-risk disease. We are the first to prospectively explore single agent bortezomib as primary therapy (response rate, maintenance and reinduction) without consolidative autologous stem cell transplant in a cohort selected to have high-risk MM. Patients received 8-cycles of induction followed by maintenance bortezomib every other week indefinitely. Patients relapsing on maintenance had full induction schedule resumed. On an intention to treat basis the response rate (>=PR) was 48%. Among 7 patients, who progressed on maintenance bortezomib and received reinduction, two responded. With a median follow-up of 48.2 months, 1- and 2-year OS probabilities were 88% (95%CI, 74–95%) and 76% (95%CI, 60–86%), respectively. Median PFS was 7.9 months (95%CI, 5.8–12.0). Twenty-three and 34 patients had >=grade 3 hematologic and non-hematologic toxicity, respectively with treatment emergent neuropathy in: 7%, motor grade 1–2; 56%, sensory grade 1–2 and 2%, grade 3; and 14%, neuropathic pain grade 1–2 in and 2%, grade 3. In high-risk patients, upfront bortezomib results in response rates comparable to those reported for unselected cohorts, but single agent bortezomib is not sufficient as primary therapy.