In 2015, the combination of bortezomib, lenalidomide, and dexamethasone (VRd) was shown to improve survival outcomes compared with lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma (MM). However, it also became known that the higher response rate of VRd increased patients’ risk for severe peripheral neuropathy. Since no test was available to guide the choice of treatment, Cleveland Clinic designed a response-adapted treatment pathway, or “carepath,” that tailors therapy according to early response end points as well as patients’ ability to pay for treatment.
Newly diagnosed patients with symptomatic, measurable MM are advised to begin a 2-drug regimen of Rd or, if cast nephropathy was suspected or lenalidomide (R) copay was too high, bortezomib (V) and dexamethasone (d). Depending on patient response, treatment intensity can be increased with the sequential addition of R or V, or cyclophosphamide followed by liposomal doxorubicin when there was inadequate response to the first regimen. Once partial response (PR) is reached, patients are evaluated for high-dose melphalan and autologous stem-cell transplantation or consolidation with their induction regimen followed by lenalidomide or bortezomib maintenance.
Over a 3-month period, the carepath was used in 91 patients. Their median age at treatment start was 64 years, 23 (28.4%) patients had high-risk cytogenetics, 33 (36%) had International Staging System stage III. Fifty-four percent of patients remained on a doublet therapy during the study period. At median follow-up of 20.5 months, at least PR was achieved in 84 (92%) patients and at least very good partial remission in 63 (69%) patients. Researchers conclude that early data support the implementation of a response-adapted strategy for newly diagnosed patients with MM. This approach achieved disease control comparable to the new standard triplet regimen VRd but requires only 2 drugs in half the patients.
Reu FJ, et al. ASH 2016. Abstract 3606.