As reported in The Lancet Oncology by Meletios A. Dimopoulos, MD, and colleagues, the phase III APOLLO trial has shown significantly improved progression-free survival with the addition of subcutaneous daratumumab to pomalidomide/dexamethasone in patients with previously treated multiple myeloma.

APOLLO Study Details

In the open-label trial, 304 patients from sites in 12 European countries were randomly assigned between June 2017 and June 2019 to receive daratumumab plus pomalidomide/dexamethasone (n = 151) or pomalidomide/dexamethasone (n = 153). Patients had received one or more previous line(s) of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to at least one previous line of antimyeloma therapy, and were refractory to lenalidomide if only one previous line of therapy had been received.

Meletios A. Dimopoulos, MD

All patients received oral pomalidomide at 4 mg once daily on days 1 to 21 and oral dexamethasone at 40 mg once daily on days 1, 8, 15, and 22 (20 mg for those aged ≥ 75 years) in 28-day cycles. Daratumumab was given at 1,800 mg subcutaneously (SC) or 16 mg/kg intravenously (IV) weekly during cycles 1 and 2, every 2 weeks during cycles 3 to 6, and every 4 weeks thereafter until disease progression or unacceptable toxicity.

All patients who started on SC daratumumab (95% of group) continued on SC administration throughout the trial. Among the seven patients (5%) starting on IV administration, four (3%) switched to SC administration.  The primary endpoint was progression-free survival on central review in the intention-to-treat population.

Survival Rates

Median follow-up was 16.9 months (interquartile range = 14.4–20.6 months). Median progression-free survival was 12.4 months (95% confidence interval [CI] = 8.3–19.3 months) in the daratumumab group vs 6.9 months (95% CI = 5.5–9.3 months) in the control group (hazard ratio [HR] = 0.63, 95% CI = 0.47–0.85, P = .0018). Kaplan-Meier estimates of rates at 18 months were 42% (95% CI = 34%–50%) vs 26% (95% CI = 18%–33%).

Overall response rates were 69% vs 46%, with complete response or better in 25% vs 4% and very good partial response or better in 51% vs 20% (all P < .0001). Median duration of response was not reached (95% CI = 15.2 months–not reached) in the daratumumab group vs 15.9 months (95% CI = 8.3–24.8 months) in the control group. At the time of progression-free survival analysis, overall survival data were not mature; death had occurred in 32% vs 33% of patients.

Median time to subsequent antimyeloma therapy was 23.2 months (95% CI = 13.8 months–not estimable) in the daratumumab group vs 11.8 months (95% CI = 8.9–15.4 months) in the control group. In a prespecified analysis, median progression-free survival after the next line of therapy was not reached (95% CI = 16.6 months–not estimable) in the daratumumab group vs 17.6 months (95% CI = 13.4 months–not estimable) in the control group (HR = 0.79, 95% CI = 0.55–1.14, P = .21).  

Adverse Events

The most common grade 3 or 4 adverse events were neutropenia (68% of daratumumab group vs 51% of control group), anemia (17% vs 21%), and thrombocytopenia (17% vs 18%). Grade 3 or 4 infections occurred in 24% vs 20% of patients, including pneumonia in 11% vs 6% and lower respiratory tract infection in 10% vs 8%. Serious adverse events occurred in 50% vs 39% of patients, with pneumonia (15% vs 8%) and lower respiratory tract infection (12% vs 9%) being the most common.

Adverse events led to discontinuation of study treatment in 2% vs 3% of patients. Infusion-related reactions—all grade 1 or 2 and all occurring with SC administration—occurred in 5% of the daratumumab group. Second primary malignancies occurred in 2% vs 2% of patients. Adverse events led to death in 7% vs 7% of patients, with death in five patients in the daratumumab group vs no patients in the control group considered at least possibly related to treatment.  

The investigators concluded, “Among patients with relapsed or refractory multiple myeloma, daratumumab plus pomalidomide and dexamethasone reduced the risk of disease progression or death vs pomalidomide and dexamethasone alone and could be considered a new treatment option in this setting.”

Dr. Dimopoulos, of National and Kapodistrian University of Athens, Alexandra Hospital, Athens, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by the European Myeloma Network and Janssen Research and Development. For full disclosures of the study authors, visit thelancet.com.