Results from two phase III clinical trials (MAIA and CASSOPIEA) evaluating daratumumab (Darzalex®) combinations for the treatment of newly diagnosed myeloma patients have been recently published. The data provide evidence to support the use of daratumumab for the treatment of newly diagnosed myeloma patients whether they are eligible for high dose therapy and stem cell transplantation (HDT-SCT) or not.
Daratumumab for treatment of newly diagnosed patients not eligible for HDT-SCT.
- Daratumumab, lenalidomide (Revlimid®) and dexamethasone (DRd) reduced the risk of disease progression by 44% compared to treatment with lenalidomide and dexamethasone (Rd) alone.
- Neutropenia and pneumonia were more common side effects in the DRd group than the Rd control group.
- The results led to FDA approval of DRd by for the treatment of newly diagnosed HDT-SCT ineligible patients.
Interim results from a randomized, open-label, phase III trial (MAIA) were recently published in the New England Journal of Medicine. The trial compared DRd to Rd for the treatment of newly diagnosed myeloma patients who were HDT-SCT ineligible. The results indicate that the addition of daratumumab to lenalidomide and dexamethasone was well tolerated and reduced the risk of disease progression in HDT-SCT ineligible patients.
The trial recruited 737 newly diagnosed myeloma patients with Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2 and were ineligible for HDT-SCT due to age (≥65 years) or comorbidities.
The median progression-free survival (PFS) was not reached in the DRd group, compared with 31.9 months in the Rd control group. At a median follow-up of 28.0 months, disease progression or death had occurred in 26.4% in the daratumumab group versus 38.8% in the control group. The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The PFS benefit of adding daratumumab to Rd was less pronounced in patients with high-risk cytogenetics.
The percentage of patients with an overall response was 92.9% in the daratumumab group and 81.3% in the control group (P<0.001). Complete response or better was achieved in 47.6% of patients in the daratumumab group compared with 24.9% in the control group (P <0.001).
The most common serious adverse effects (grade 3 or 4) were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anaemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%). Infusion-related reactions associated with daratumumab were reported in 40.9% of the patients in the daratumumab group.
Daratumumab for treatment of newly diagnosed patients eligible for HDT-SCT.
- Daratumumab, bortezomib (Velcade®), thalidomide and dexamethasone (D-VTd) before and after HDT-SCT increased complete response rates when compared to treatment with bortezomib, thalidomide and dexamethasone (VTd) before and after HDT-SCT.
- The most common serious side effects were neutropenia, lymphopenia and stomatitis.
- The use of D-VTd before and after HDT-SCT in newly diagnosed myeloma patients has been granted a priority review by the FDA
Results from the first part of phase III clinical trial (CASSOPIEA) investigating the benefit of treatment with D-VTd before and after HDT-SCT in newly diagnosed myeloma patients have been published in The Lancet.
The randomized, open-label trial compared the safety and efficacy of treatment with D-VTd or VTd before and after HDT-SCT in newly diagnosed myeloma patients (n=1085).
The results showed the addition of daratumumab to VTd improved responses rates. At day 100 after transplantation, 29% patients in the D-VTd group and 20% in the VTd group had achieved a stringent complete response (odds ratio 1·60, 95% CI 1·21–2·12, p=0·001). 64% of patients in D-VTd group achieved minimal residual disease-negativity versus 44% of patients in the VTd control group (p<0·0001). Median progression-free survival was not reached in either group (hazard ratio 0·47, 95% CI 0·33–0·67, p<0·0001).
The most common serious adverse events (grade 3 or 4) were neutropenia (28% vs 15%), lymphopenia (17% vs 10%), and stomatitis (13% vs 16%). Infusion-related reactions associated with daratumumab were reported in 35% of the patients in the daratumumab group.
These results add to the growing evidence showing the benefit of daratumumab which already has several approved indications in the UK for the treatment of relapsed/refractory patients with multiple myeloma. This includes the most recent approval of daratumumab, bortezomib and dexamethasone at second-line.