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Summary Once-weekly administration of bortezomib has reduced bortezomib-induced peripheral neuropathy without affecting response rates, but this has only been demonstrated prospectively in three- and four- drug combinations. We report a phase II trial of alternate dosing and schedule of bortezomib and dexamethasone in newly diagnosed multiple myeloma patients who are not eligible for or refused autologous stem cell transplantation. Bortezomib 1·6 mg/m2 intravenously was given once-weekly for six cycles, together with dexamethasone 40 mg on the day of and day after bortezomib. Fifty patients were enrolled; 58% did not require any dose modification. The majority of patients had multiple co-morbidities, including cardiovascular (76%) and renal insufficiency (54%), and the median number of medications prior to enrollment was 13. Of all evaluable patients, the overall response rate was 79% and at least 45% had at least a very good partial response. The median time to first response was 1·3 months (range, 0·25–2·4 months). The progression-free and overall survivals were 8 months and 46·5 months, respectively. Twenty-four percent developed worsening neuropathy. We conclude that alternate dosing and scheduling of bortezomib and dexamethasone is both safe and effective for management of newly diagnosed multiple myeloma in frail patients. (ClinicalTrials.gov number, NCT01090921).

Multiple myeloma (MM), a heterogeneous plasma cell dyscrasia with a variety of clinical presentations and outcomes, is undergoing a treatment renaissance. While new drug classes have been discovered, a subset of high-risk MM remains relatively refractory to treatment. Current risk stratifications models, such as Durie-Salmon and the International Staging System, estimate disease burden and prognosis. Cytogenetics and gene expression profiles can help further identify more aggressive disease. Additionally, molecular and immunophenotypic assessment of minimal residual disease (MRD) and different imaging studies can identify patients at higher risk for relapse. It is now an opportune time to develop algorithms to combine all of the currently available clinical and genomic information to begin to inform specific therapeutic intervention in individual patients or at least smaller subgroups with similarly behaving disease.