In 2015, the combination of bortezomib, lenalidomide, and dexamethasone was shown to improve survival outcomes versus lenalidomide and dexamethasone alone in patients with newly diagnosed multiple myeloma. However, this triplet therapy also increased patients’ risk for severe peripheral neuropathy.
Because no test is available to guide the choice of treatment, the Cleveland Clinic designed a response-based treatment pathway, or “carepath,” that tailors therapy according to early response end points as well as patients’ ability to pay for treatment.
In the carepath, newly diagnosed patients with symptomatic, measurable multiple myeloma are advised to begin a 2-drug regimen of lenalidomide and dexamethasone. If cast nephropathy is suspected or the lenalidomide copay is too high, treatment with bortezomib and dexamethasone would begin.
Depending on patient response, treatment intensity can be increased with the sequential addition of lenalidomide or bortezomib, or cyclophosphamide followed by liposomal doxorubicin when the patient has an inadequate response to the first regimen.
Once patients achieve partial responses, they are evaluated for 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; of these, 23 (28.4%) patients had high-risk cytogenetics and 33 (36%) had International Staging System stage III. During the study, 54% of patients remained using a doublet therapy.
At a median follow-up of 20.5 months, 84 (92%) patients achieved at least a partial response, 63 (69%) achieved at least very good partial remission, and 6 (7%) achieved complete remission documented by bone marrow exam.
The researchers concluded that early data support the implementation of this response-adapted strategy for newly diagnosed patients with multiple myeloma. This approach achieved disease control comparable to the new standard triplet regimen bortezomib, lenalidomide, and dexamethasone but requires only 2 drugs in half the patients.