A triple combination of Darzalex (daratumumab), Velcade (bortezomib), and dexamethasone will be available on the National Health Service (NHS) in England for the treatment of relapsed or refractory multiple myeloma patients.
The U.K.’s National Institute of Health and Care Excellence (NICE) decided to approve the therapy based on findings from the CASTOR Phase 3 trial (NCT02136134), in which the Darzalex combination reduced the risk of disease worsening or death by 61% compared to the other two therapies alone. The triple therapy will be paid for through the Cancer Drugs Fund.
In a press release, Rose Gray, Cancer Research UK’s policy manager, said the approval is “brilliant news” for people with myeloma and mentioned the work by NHS England, NICE, and Janssen — Darzalex’s developer — in obtaining this approval.
“NICE has said it’s not yet sure how much this treatment will extend patients’ lives, but by recommending it for the Cancer Drugs Fund, patients will have access to it while more data is collected on its long-term benefits,” Gray said.
CASTOR included 498 myeloma patients who had received at least one prior line of therapy and had achieved at least a partial response to one such treatment. Participants were assigned randomly to standard treatment with Velcade plus the immunosuppressant dexamethasone, given with or without Darzalex.
The main goal was to determine if Darzalex extended the time patients lived without signs of disease worsening. Secondary measures included the time to disease progression, amount of patients achieving a response to treatment, percentage of patients achieving minimal residual disease, and overall survival.
Investigators found that after one year, more patients given Darzalex remained alive and without disease progression (60.7%) compared to those on standard treatment only (26.9%). Also, the median progression-free survival in the 247 patients without Darzalex was 7.2 months, but had not been reached in the 251 participants on Darzalex, which means they were still responding to the treatment.
Adding Darzalex also led to better overall response (82.9% vs. 63.2%), very good partial response or better (59.2% vs. 29.1%) and complete response rates (19.2% vs. 9.0%). (Complete response refers to the disappearance of all cancer signs.)
As for safety, treatment with Darzalex was associated with more frequent peripheral sensory neuropathy, or nerve damage (47.3% vs. 37.6%), as well as higher rates of thrombocytopenia (58.8% vs. 43.9%), neutropenia (17.7% vs. 9.3%), and lymphopenia (13.2% vs. 3.8%), which mean lower-than-normal amounts of platelets, neutrophils and lymphocytes, respectively. However, the percentage of patients who discontinued treatment due to at least one adverse side effect was similar in the two groups.
Updated results revealed that after a median follow-up of 19.4 months, most patients in each treatment group were still alive, but an exploratory analysis suggested that more patients on Darzalex were alive at 24 months.
Darzalex, first developed by Genmab, is an antibody that targets a cell surface protein called CD38, found at high numbers in multiple myeloma cells. By binding to CD38, Darzalex is intended to ultimately cause myeloma cell death.
In the U.S., the combination of Darzalex, Velcade, and dexamethasone for patients who had had one previous therapy was approved in November 2016. But in the U.K, NICE initially rejected the combination due to concerns about the treatments’ cost-effectiveness.