Age no barrier to daratumumab efficacy in multiple myeloma
The addition of daratumumab to bortezomib, melphalan, and prednisone (VMP) led to improved progression-free survival (PFS) over VMP alone in elderly patients newly diagnosed with multiple myeloma (MM), reflecting the results of the overall ALCYONE* study population.
“Efficacy of D-VMP** in patients aged ≥75 years of age was consistent with the intention to treat population,” said Professor Michele Cavo from the University of Bologna in Bologna, Italy, who presented the results at EHA 2018.
“[The results showed that] combining daratumumab with VMP provides significant clinical benefit, regardless of age,” he said.
The overall study population comprised 706 adult patients (aged ≥18 years) ineligible for autologous stem cell transplantation (ASCT) who were randomized to receive nine cycles of VMP (bortezomib 1.3 mg/m2 BIW on cycle 1 and QW in cycles 2–9; melphalan 9 mg/m2 on days 1–4; and prednisone 60 mg/m2 on days 1–4) either alone (n=356) or in addition to daratumumab (16 mg/kg QW in cycle 1 and Q3W in cycles 2–9; n=350). In the D-VMP group, daratumumab was administered until disease progression or unacceptable toxicity. In this analysis, researchers compared the outcomes of treatment in elderly patients (aged ≥75 years; n=211, 104 and 107 assigned to D-VMP and VMP, respectively) with that of non-elderly patients (aged <75 years; n=495, 246 and 249 assigned to D-VMP and VMP, respectively). Patients on D-VMP and VMP were treated for a median 14.5 and 12.0 months, respectively.
Efficacy comparable with that of overall population
After a median 16.5-month follow-up period, the risk of disease progression or death was reduced by 47 percent among patients aged ≥75 years treated with D-VMP over those treated with VMP (median PFS, not reached vs 20.4 months, hazard ratio [HR], 0.53, 95 percent confidence interval [CI], 0.32–0.85). [EHA 2018, abstract S107]
Patients aged <75 years also fared better on D-VMP with a 51 percent reduced risk of progression or death compared with those treated with VMP (median PFS, not reached vs 17.9 months, HR, 0.49, 95 percent CI, 0.36–0.68).
These findings were comparable with those of the overall population, where patients on D-VMP had a 50 percent reduction in risk of progression or death than those on VMP (median PFS, not reached vs 18.1 months, HR, 0.50, 95 percent CI, 0.38–0.65; p<0.0001).
Overall response rates were significantly higher among D-VMP recipients compared with VMP recipients be it in the overall population (91 percent vs 74 percent; p<0.0001), patients aged ≥75 years (88 percent vs 70 percent; p=0.0021), or patients aged <75 years (92 percent vs 76 percent; p<0.0001), with consistently higher complete response or better rates (43 percent vs 24 percent, 41 percent vs 24 percent, and 43 percent vs 25 percent in the overall population, aged ≥75 years, and aged <75 years groups, respectively).
Rates of minimal residual disease (MRD) negativity (10–5 threshold) were also higher among D-VMP compared with VMP recipients in patients aged ≥75 years (24 percent vs 8 percent) and <75 years (22 percent vs 6 percent).
Tolerable safety profile
The most common (≥10 percent) grade 3–4 treatment-emergent adverse events (TEAEs) experienced by patients aged ≥75 years in the D-VMP vs VMP groups were neutropenia, thrombocytopenia, and anaemia (52 percent vs 42 percent, 51 percent vs 43 percent, and 24 percent vs 23 percent, respectively).
Patients on D-VMP were less likely to develop grade 3–4 peripheral sensory neuropathy than those on VMP (1 percent vs 4 percent, 0 percent vs 6 percent, and 2 percent vs 3 percent of patients in the overall, aged ≥75 years, and aged <75 years groups, respectively), while the incidence of grade 3–4 infections in patients aged ≥75 years was comparable with that of the overall population (28 percent vs 23 percent).
Treatment discontinuation due to TEAEs was lower in D-VMP than VMP recipients be it among patients aged ≥75 years (8 percent vs 16 percent) or <75 years (4 percent vs 6 percent), while 36 and 24 percent of patients on D-VMP aged ≥75 years and <75 years, respectively, experienced infusion-related reactions with a majority occurring during the first infusion.
D-VMP exhibited acceptable tolerability in all age groups, with no new safety signals emerging, a low rate of grade 3–4 peripheral sensory neuropathy, and comparable grade 3–4 infection rates between elderly patients and the overall population, said Cavo.
Potential treatment for elderly patients
“The risk of MM increases with age … and approximately one-third of patients will receive their diagnosis when they are older than 75 years,” said Cavo.
“Elderly patients typically have decreased performance status and increased comorbidities and both these findings affect their ability to … tolerate treatments,” he said. They are also typically excluded from ASCT, with VMP being the standard-of-care treatment, he said.
“This sub-analysis of the [ALCYONE] study supports the efficacy of D-VMP in patients aged ≥75 years,” said Cavo.