Daratumumab regimen extends PFS among certain patients with relapsed or refractory myeloma
The addition of daratumumab to pomalidomide and dexamethasone extended PFS among patients with relapsed or refractory multiple myeloma who were refractory to lenalidomide, according to a study presented at ASH Annual Meeting and Exposition.
The safety profile of the combination appeared consistent with previous reports for subcutaneous daratumumab (Darzalex, Janssen), pomalidomide (Pomalyst, Bristol Myers Squibb) and dexamethasone, results of the phase 3 APOLLO study showed.
“In the primary analysis of the phase 3 APOLLO study, with median follow-up of 16.9 months, the addition of subcutaneous daratumumab to pomalidomide and dexamethasone showed a significant PFS benefit over pomalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma,” Pieter Sonneveld, MD, PhD, head of the department of hematology at Erasmus MC Cancer Institute and professor of hematology at Erasmus University of Rotterdam in The Netherlands, said during the presentation.
“The objective of this study,” Sonneveld continued, “was to evaluate the efficacy and safety of daratumumab plus pomalidomide and dexamethasone vs. pomalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma in APOLLO, with an additional 13.8 months of follow-up since the primary analysis.”
The analysis included 304 adults with relapsed or refractory multiple myeloma who had received at least one prior line of therapy, including a proteosome inhibitor and lenalidomide (Revlimid, Bristol Myers Squibb), and had responded to treatment. Patients with only one previous line of therapy had to be refractory to lenalidomide for inclusion.
Sonneveld and colleagues randomly assigned patients 1:1 to daratumumab plus pomalidomide and dexamethasone (n = 151; median age, 67 years; range, 42-86; 79.5% refractory to lenalidomide) or pomalidomide and dexamethasone (n = 153; median age, 68 years; range, 35-90; 79.7% refractory to lenalidomide). Researchers stratified patients by disease stages (I vs. II vs. III) and number of lines of therapy (1 vs. 2-3 vs. 4).
All patients received 28-day cycles of oral pomalidomide, dosed at 4 mg daily on days 1 to 21, and oral dexamethasone, dosed at 40 mg (20 mg for patients aged 75 years or older) daily on days 1, 8, 15 and 22.
Patients in the daratumumab group also received daratumumab subcutaneously (1,800 mg; co-formulated with recombinant human hyaluronidase PH20) or, prior to a protocol amendment, via IV (16 mg/kg; n = 7) weekly during cycles 1 to 2, every 2 weeks during cycles 3 to 6, and every 4 weeks thereafter. Those who received daratumumab via IV were allowed to switch to subcutaneous daratumumab starting on day 1 of cycle 3 or later.
Among patients who were refractory to lenalidomide, the last dose of lenalidomide received was 5 mg to 10 mg for 30 patients (25%) in the daratumumab-pomalidomide-dexamethasone group and 31 patients (25.4%) in the pomalidomide-dexamethasone group; and 15 mg to 25 mg for 86 patients (71.7%) in the daratumumab-pomalidomide-dexamethasone group and 89 patients (73%) in the pomalidomide-dexamethasone group.
All patients underwent treatment until disease progression or unacceptable toxicity.
Sonneveld reported 106 patients from the daratumumab-pomalidomide-dexamethasone group and 134 from the pomalidomide-dexamethasone group discontinued treatment, most because of progressive disease.
PFS served as the primary endpoint. Median follow-up was 30.7 months.
Results showed median PFS of 12.1 months in the daratumumab-pomalidomide-dexamethasone group vs. 7 months in the pomalidomide-dexamethasone group (HR = 0.63; 95% CI, 0.48-0.83). The estimated 18-month PFS rate in the intention-to-treat population was 40.9% with the daratumumab regimen vs. 25.5% with pomalidomide and dexamethasone alone.
The daratumumab regimen also conferred longer median PFS among patients refractory to lenalidomide (9.9 months vs. 6.5 months; HR = 0.64; 95% CI, 0.48-0.86), and lenalidomide-refractory patients who last received a lenalidomide dose of 5 mg to 10 mg (10.3 months vs. 8.5 months; HR = 0.83; 95% CI, 0.47-1.45) or 15 mg to 25 mg (10.7 months vs. 6.5 months; HR, 0.56; 95% CI, 0.39-0.8).
“The responses continued to deepen with extended follow-up,” Sonneveld said. “No new safety concerns were observed with extended follow-up.”
Researchers observed grade 3 or higher treatment-emergent adverse events among 133 patients (89.3%) in the daratumumab-pomalidomide-dexamethasone group and 123 patients (82%) in the pomalidomide-dexamethasone group. They included neutropenia (69.1% with daratumumab vs. 50.7% without it), thrombocytopenia (18.1% vs. 18.7%) and anemia (18.1% vs. 21.3%). Grade 3 to grade 4 pneumonia occurred in nearly twice as many patients in the daratumumab group (15.5% vs. 8.7%). Seventy-six patients (51%) in the daratumumab-pomalidomide-dexamethasone group and 61 patients (40.7%) in the daratumumab plus pomalidomide group had serious adverse events.
“With extended follow-up of the phase 3 APOLLO study, adding daratumumab subcutaneously to pomalidomide and dexamethasone continued to demonstrate a PFS benefit and to achieve deeper responses vs. pomalidomide and dexamethasone alone in patients with relapsed or refractory multiple myeloma,” Sonneveld said.
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Sonneveld P, et al. Abstract 2747. Presented at: ASH Annual Meeting and Exposition. Dec. 11-14, 2021; Atlanta.
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