Key Messages
- Canada’s Drug Agency (CDA-AMC) recommends that Darzalex SC (daratumumab) in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) be reimbursed by public drug plans for the treatment of adult patients with newly diagnosed multiple myeloma (NDMM) who are not suitable for autologous stem cell transplant (ASCT) or for whom ASCT is not planned as the initial treatment, if certain conditions are met.
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The pan-Canadian Oncology Drug Review Expert Review Committee (pERC) determined that D-VRd demonstrates acceptable clinical value versus the combination of bortezomib, lenalidomide, and dexamethasone (VRd) in patients with NDMM who are not candidates for ASCT. Evidence from a clinical trial (CEPHEUS; N = 395) demonstrated that when compared to VRd, D-VRd given for 58 months prolonged the time until disease progression or death and was associated with an improved response to treatment in patients with NDMM who are not candidates for ASCT. Evidence from indirect treatment comparisons (ITCs) showed that in these patients, time to disease progression or death and response to treatment were improved with D-VRd when compared to daratumumab in combination with lenalidomide and dexamethasone (DRd) or compared with daratumumab in combination with bortezomib, melphalan, and prednisone (DVMp). However, the magnitude of benefit is uncertain, mainly due to differences in patients’ baseline characteristics between the clinical trials included in the ITCs. Evidence from ITCs also showed that time to disease progression or death and response to treatment were similar between groups receiving D‑VRd or the combination of isatuximab with VRd (Isa-VRd).
In the CEPHEUS trial, there was a large amount of missing data for health-related quality of life (HRQoL) outcomes; therefore, the clinical value of the improvements in HRQoL associated with D-VRd cannot be determined. Additionally, Darzalex SC was considered an additive therapy to VRd, and there were higher incidences of serious adverse events (AEs), infections and infestations, and low levels of certain blood cells associated with D-VRd.
- Darzalex SC should only be reimbursed for adult patients with NDMM who are not suitable for ASCT or do not plan to receive ASCT as the initial treatment. Patients should also have good performance status and must not have received prior treatments for multiple myeloma. They also should not have signs of meningeal involvement of multiple myeloma.
- Darzalex SC should only be reimbursed if prescribed in combination with VRd, if prescribed by clinicians with expertise in diagnosis and management of multiple myeloma, and if the cost of Darzalex SC is reduced.