The APOLLO trial previously showed that adding daratumumab to pomalidomide and dexamethasone significantly improves the progression-free survival of patients with relapsed/refractory multiple myeloma. While the updated results of this trial did not show a significant survival difference between the study arms, long-term safety data continue to support the use of daratumumab plus pomalidomide and dexamethasone in this patient population.
Immunomodulatory drug-based regimens are a standard approach in the management of relapsed or refractory multiple myeloma (R/R MM). Daratumumab is a human IgGκ monoclonal antibody that targets CD38 with a direct on-tumour and immunomodulatory mechanism of action. Based on the encouraging results of the APOLLO trial, the combination of intravenous daratumumab plus pomalidomide and dexamethasone was approved to treat R/R MM patients who received at least two previous lines of therapy, including lenalidomide and a proteasome inhibitor. In the primary analysis of this trial, adding daratumumab to pomalidomide and dexamethasone significantly improved the progression-free survival (PFS) in this patient population. This article reports the final overall survival (OS) data and updated safety findings from the APOLLO study.
The phase 3 APOLLO trial was conducted across 48 academic centres and hospitals in 12 European countries. Eligible patients were adults (≥18 years) with R/R MM who had received at least one previous line of therapy, including lenalidomide and a proteasome inhibitor, had a partial response or better to one or more prior lines, and were refractory to lenalidomide if they had received only one previous line of therapy. In total, 304 patients were randomly assigned (1:1) to receive daratumumab plus pomalidomide and dexamethasone (n=151) or pomalidomide and dexamethasone (n=153). The primary endpoint was PFS and was previously reported. The secondary endpoint of overall survival (OS) was assessed in this analysis.
After a median follow-up of 39.6 months, the results did not reveal a significant difference in OS between the two treatment arms, although a numerical benefit was observed in patients who received the triplet therapy (34.4 vs. 23.7 months in patients receiving only pomalidomide and dexamethasone, respectively; HR[95%CI]: 0.82[0.61-1.11]; p=0.20). The most common grade 3-4 treatment-emergent adverse events (AEs) were neutropenia (69% vs. 51% of patients receiving pomalidomide and dexamethasone with or without daratumumab, respectively), anaemia (18% vs. 21%), and thrombocytopenia (18% vs. 19%). Serious treatment-emergent AEs occurred in 54% vs. 40% of patients, with pneumonia being the most common (15% vs. 9% in patients receiving triplet or doublet therapy, respectively). Treatment-emergent AEs resulting in death occurred in 9% of patients in both groups. In the triplet arm, 3% of AEs leading to death within 30 days of the last treatment dose were associated with the study treatment, including septic shock (n=1), sepsis (n=1), bone marrow failure, campylobacter infection, and liver disorder (n=1), and pneumonia (n=1). No AE was associated with the study treatment in the pomalidomide and dexamethasone group.
While the difference in OS between the treatment arms did not reach statistical significance, the enduring safety profile, as demonstrated through long-term follow-up, reinforces the rationale for using daratumumab in combination with pomalidomide and dexamethasone for patients with R/R MM.
Dimopoulus MA, Terpos E, Boccadoro M, et al. Subcutaneous daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (APOLLO): extended follow-up of an open-label, randomised, multicentre, phase 3 trial. Lancet Haematol. 2023;10(10):e813-e24.