1st-line treatment approval
The Food and Drug Administration (FDA), USA, approval of Darzalex (daratumumab) for multiple myeloma as 1st line treatment was based on one open-label, active-controlled, phase 3 study (ALCYONE (NCT02185479)). This study involved a total of 706 patients with newly diagnosed multiple myeloma. Patients were divided into two groups and took the combination of bortezomib, melphalan, and prednisone with or without the addition of Darzalex (daratumumab). Patients continued treatment until disease progression or unacceptable toxicity1.
Among the efficacy outcome measures were the overall response and minimal residual disease (MRD)- negativity. MRD is the presence of small numbers of cancerous cells that remain in the patient although there are no signs or symptoms of the disease. MRD is the major cause of relapse.
The study ALCYONE demonstrated an improvement in progression-free survival in the patient group that added Darzalex (daratumumab) to their treatment plan. The reduction of risk of disease progression was 50% in this group.
The overall response was:
The MRD-negativity rate was:
Over all patients: 22.3% [95% CI: 18, 27] with the addition of daratumumab vs. 6.2% [95% CI: 3.9, 9.2]
In patients with complete response: 49.7% [95% CI: 41.4, 58] vs. 25.3% [95% CI: 16.6, 35.7]
2nd-line treatment approval
The approval of daratumumab in combination with lenalidomide and dexamethasone was based on a study which compared treatment with daratumumab in combination with lenalidomide and dexamethasone (DLD) (N = 286) to lenalidomide and dexamethasone (LD) alone (N = 283) in 569 patients with multiple myeloma who had received at least one prior treatment. The OS in the DLD was 91.3% vs 74.6%. The median progression free survival (mPFS) was 18.4 months in the LD group while it was not reached in the DLD arm. The risk of disease progression or death in the DLD group was reduced by 63% in the DLD arm compared to the LD arm1.
The approval of daratumumab in combination with bortezomib and dexamethasone was based on a study which compared treatment with daratumumab in combination with bortezomib and dexamethasone (DBD) (N = 251) to bortezomib and dexamethasone (BD) alone (N = 247) in 498 patients with multiple myeloma who had received a median of 2 prior treatments. The mPFS was 7.2 months in the BD group while it was not reached in the DBD arm. The risk of disease progression or death in the BD group was reduced by 61% in the DBD arm compared to the BD arm1.
The approval of daratumumab as combination treatment with pomalidomide and dexamethasone were based on an open-label trial (EQUULEUS - NCT01998971). This study included 103 patients with multiple myeloma who had received a prior proteasome inhibitor and an immunomodulatory agent. Patients received 16 mg/kg Darzalex (daratumumab) in combination with pomalidomide and low-dose dexamethasone until disease progression1.
Among the efficacy outcome measures were the overall response rate, the median time to response and the median duration of response1.
The overall response rate was:
The median time to response was:
The median duration of response was:
4th-line treatment approval
The approvals of daratumumab as monotherapy were partly based on two studies that returned positive results. In study MMY2002 31 of the 106 patients treated with daratumumab experienced a complete or partial reduction in their tumour burden (overall response rate (ORR) = 29.2%; 95% confidence interval (CI) 20.8, 38.9), which lasted for an average of 7.4 months6,1,3. The median overall survival (OS) was 17.5 months3. The second study (GEN501), involving 42 participants, resulted in a complete or partial reduction of the tumour for 36% of the patients. The median duration of response was not reached and after 15.2 months 74% of the patients were still alive3.