Adding daratumumab to bortezomib and dexamethasone for multiple myeloma

This paper studied the effects of daratumumab in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma.  Daratumumab in combination with bortezomib and dexamethasone led to a longer survival period without worsening disease. 

Multiple myeloma is a cancer of the bone marrow. Some patients may experience a recurrence of the myeloma after their initial treatment. This is known as relapsed multiple myeloms. Other patients may not respond to treatment. This is known as refractory multiple myeloma. New treatment options are needed for patients who have recieved multiple prior treatments.

Daratumumab (Darzalex) is a new treatment option for multiple myeloma. It is an antibody that attaches to a protein on the myeloma cell, leading to cell death. It is not clear whether this treatment is effective in pretreated patients when combined with other common treatments, such as the chemotherapy bortezomib (Velcade) or the steroid dexamethasone (Ozurdex).

498 patients with relapsed or refractory multiple myeloma who had received at least one previous type of therapy and had at least a partial response to previous therapy were studied. 251 patients were randomly assigned to treatment with daratumumab in combination with bortezomib and dexamethasone (group 1). 247 patients were randomly assigned to treatment with bortezomib and dexamethasone alone (group 2).  

30.5% of group 1 and 43.9% of group 2 stopped treatment because of worsening disease or side effects. At 12 months, the rate of progression-free survival (time from treatment until disease progression or death) was 60.7% among patients in group 1 and 26.9% in patients in group 2. Patients in group 1 had a 61.4% lower risk of disease progression or death that patients in group 2. 82.9% of patients in group 1 responded to treatment, compared to 63.2% of group 2.

98.8% of patients in group 1 and 95.4% of patients in group 2 had at least one adverse event (undesired effect of treatment). The rate of more severe adverse events was 76.1% in patients in group 1 and 62.4% in patients in group 2. The most common more severe adverse event was low levels of platelets (cells invovled in blood clotting), white blood cells, and red blood cells. This effect was more common in patients treated with daratumumab. 

The authors concluded that among patients with relapsed or refractory multiple myeloma, adding daratumumab to bortezomib and dexamethasone led to a longer progression-free survival, but was associated with higher rates of low blood count.