While there was no significant difference in overall survival between the daratumumab and control groups, safety profile results and follow-up data support daratumumab’s continued evaluation in relapsed/refractory multiple myeloma.
Daratumumab (Darzalex) used in combination with pomalidomide (Pomalyst) and dexamethasone did not deliver significant improvements in overall survival (OS) for patients with relapsed/refractory multiple myeloma (MM), but its use is still safe, according to a study published in The Lancet.1
The APOLLO study (NCT03180736)—an extended follow-up of an open-label, randomized, multicenter, phase 3 trial—was conducted across 12 European countries. The median follow-up was 39.6 months (interquartile range [IQR], 37.1-43.7), and median OS(mOS) was 34.4 months (95% CI, 23.7-40.3) in the daratumumab plus pomalidomide and dexamethasone group. In contrast, mOS was 23.7 months (19.6-29.4) in the pomalidomide and dexamethasone group (HR, 0.82; 95% CI, 0.61-1.11; P =.20).
“Although the difference in overall survival observed between treatment groups was not significant, the safety profile results with long-term follow-up reported here continue to support the use of daratumumab plus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma,” study authors wrote.
Between June 2017 and June 2019, 304 patients were enrolled in the study. The daratumumab plus pomalidomide and dexamethasone group consisted of 151 patients, and the pomalidomide and dexamethasone group consisted of 153 patients. The median age was 67 years (IQR, 60-72). One-hundred and forty-three patients (47%) were female, 161 (53%) were male, and 272 (89%) were White.1
The primary end point of the study was progression-free survival (PFS), which was previously reported in The Lancet. PFS in the daratumumab with pomalidomide and dexamethasone was 12.4 months (95% CI, 8.3-19.3) vs 6.9 months (5.5-9.3).2
To be eligible for the study, patients had to have an ECOG performance status of 0-2, received at least 1 previous line of therapy (including lenalidomide [Revlimid] and a proteasome inhibitor), had a partial response or better to at least 1 previous line of therapy, and were refractory to lenalidomide if they had received only 1 previous line of therapy.
Four mg of pomalidomide was administered once daily on days 1-21, and 40 mg of oral dexamethasone was administered on days 1, 8, 15, and 22. These administrations were given in 28-day cycles until disease progression or unacceptable toxicity. Daratumumab was administered subcutaneously (1800 mg) or intravenously (16 mg/kg) weekly for cycles 1-2, every 2 weeks for cycles 3-6, and every 4 weeks thereafter.
Neutropenia was the most common grade 3-4 treatment-emergent adverse event (TRAE) in the daratumumab arm (103 [69%] of 149) compared with the observation arm (76 [51%] of 150). Other TRAEs included anemia (27 [18%] v 32 [21%]) and thrombocytopenia (27 [18%] v 28 [19%]). Serious TRAEs were observed in 80 patients (54%) in the daratumumab arm vs 60 (40%) in the observation arm. TRAEs leading to death occurred in 13 patients (9%) in the daratumumab arm vs 13 patients (9%) in the observation arm.1
Other studies are further exploring the role of daratumumab in MM treatment. These include DILEMMA (NCT05835726), DART4MM (NCT03992170), and PREDATOR (NCT0369755).