Evaluating real-world outcomes of daratumumab in patients with multiple myeloma.

This study evaluated the effectiveness of daratumumab (Darzalex)-based therapy for patients with multiple myeloma (MM) in a real-world setting. The data showed that daratumumab-based therapy in a real-world setting was not as effective as in clinical trials.

Multiple myeloma (MM) is a type of cancer that comes from blood cells called plasma cells. Considerable progress has been made in the treatment of MM with proteasome inhibitors (PI) such as bortezomib (Velcade) and immunomodulators (IM) such as lenalidomide (Revlimid). Proteasomes are large molecules present in all body cells. They break down and remove damaged proteins. MM cells rely on proteasomes to multiply and spread. PI blocks the action of proteasomes, therefore preventing myeloma cells from growing and multiplying. IM stimulates the immune system and can help to block cancer growth. However, relapses (the tumor grows after treatment) are quite common.

Daratumumab is an immunotherapy drug which directly targets the cancer cells to kill them. Daratumumab combined with PIs or IMs has been previously shown to improve the survival outcomes in patients with previously treated unresponsive MM. However, in clinical trials, patients are carefully selected to be fit and without additional medical conditions. Older patients and those with other medical conditions are commonly excluded. Therefore, the effectiveness of daratumumab­-based therapy in real-world patients with MM is not known.

The study involved 635 patients with MM. Patients were divided into 4 groups based on the treatment combinations they received. Group 1 included 176 patients who received daratumumab alone. Group 2 included 364 patients who received daratumumab combined with IM. Group 3 included 71 patients who received daratumumab combined with PI. Group 4 included 24 patients who received daratumumab plus other combinations. The average follow-up time was 18 months.

The average number of lines of therapy given before daratumumab was 5 for group 1, 3 for group 2, 4 for group 2, and 2 for group 4.

The overall response rate (ORR; partial or complete disappearance of cancer) was 44.9% for group 1, 80.5% for group 2, 60.6% for group 3, and 54.2% for group 4.

The average time until a need for further treatment was 4.9 months for group 1, 16.1 months for group 2, 5.3 months for group 3, and 5.6 months for group 4.

Daratumumab when used in early lines of therapy was associated with better outcomes. Patients with a high risk of chromosomal abnormalities had worse outcomes, but patients with amplification 1q had similar outcomes to standard-risk patients.

This study concluded that daratumumab-based therapy in real-world patients with MM was not as effective as in clinical trials. Daratumumab provided the most benefit when used in combination with IMs and in early lines of therapy.

This study only included patients from Denmark. The follow-up time was too short. It also included a high number of patients with a high risk of chromosomal abnormalities.