Meletios A. Dimopoulos, MD, of the National and Kapodistrian University of Athens in Greece, discusses outcomes from the phase III APOLLO, presented at the ASH Annual Meeting & Exposition, that assessed the efficacy of the addition of daratumumab to pomalidomide and dexamethasone in relapsed/refractory multiple myeloma.
DocWire News: Can you give an overview of the study design of the phase III APOLLO study and highlight its findings?
Dr. Dimopoulos: This is a prospective, randomized trial for patients with relapsed and/or refractory myeloma who have received at least one line of prior therapy, which included bortezomib and lenalidomide. A total of 300 patients were randomized on a 1:1 basis to receive either pomalidomide and low-dose dexamethasone or the same combination with the addition of subcutaneous daratumumab. In both arms, treatment was continued until there was evidence of disease progression or unacceptable toxicity. Patient and disease characteristics were well-balanced, with a median age of 67 years. Median prior lines of therapy was two, and 10% of the patients had received one prior line of therapy. A total of 65% of the patients were refractory to both lenalidomide and bortezomib. The main endpoint of the study was progression-free survival (PFS). This endpoint was met, with an improvement of PFS in favor of the triplet [therapy], with a median PFS of 12.4 months versus 6.9 months for pomalidomide and low-dose dexamethasone [alone].
The hazard ratio was 0.63, indicating that there was a 37% decrease of progression or death in favor of the combination of subcutaneous daratumumab with pomalidomide and low-dose dexamethasone. PFS benefit was seen across all pre-specified subgroups, and more specifically for patients refractory to lenalidomide, the hazard ratio was 0.36.
Response rate was also improved with administration of subcutaneous daratumumab with pomalidomide and low-dose dexamethasone, with response rate of 69% versus 46% in the control arm (doublet arm). Minimal residual disease negativity was 9% versus 2%, respectively.
The toxicity profile was consistent with the known safety profile of subcutaneous daratumumab and pomalidomide and low-dose dexamethasone alone. The side effects were equally distributed among the two groups, with the exception of more leukopenia, febrile neutropenia, and pneumonias occurring in the combination of pomalidomide-dexamethasone with subcutaneous daratumumab. The side effects leading to treatment discontinuation was low in both arms. Infusion-related reactions occurred in only 5% of the patients receiving the subcutaneous daratumumab combination, and it was grade 1 or two.
DocWire News: Daratumumab plus pomalidomide and dexamethasone is FDA-approved for patients with relapsed/refractory multiple myeloma who have received two or more lines of therapy. The APOLLO study assessed this regimen in patients who have received one or more lines of therapy. Do you think the study results indicate this regimen could be used earlier in more patients?
Dr. Dimopoulos: Yeah, absolutely. I think that this is a suitable combination for patients who, for example, receive a frontline treatment with bortezomib, lenalidomide, and dexamethasone, which is a frequently used regimen in the United States. Every study provides evidence that this combination could be used as a second-line treatment. Furthermore, these prospective, randomized trial data will be available to other regulatory authorities and we expect that this combination will be approved by European Medicines Agency as well.
DocWire News: How could the triplet regimen of daratumumab, pomalidomide, and dexamethasone being available earlier for patients impact treatment and outcomes in this patient population?
Dr. Dimopoulos: We have a combination which appears to be effective when given later in the course of the disease. We have data about the patients who have received only one prior line of therapy, and I believe that this combination may be better tolerated and more effective when used as soon as resistance to key treatment drugs, such as bortezomib and lenalidomide, is observed.