Subcutaneous daratumumab with pomalidomide and dexamethasone (D-Pd) is an effective and convenient treatment for patients with relapsed or refractory multiple myeloma who have received at least one line of therapy, including lenalidomide and a proteasome inhibitor.
Speaking at the 62nd ASH Annual Meeting, Professor Meletios Dimopoulos presented the findings of the phase 3 APOLLO study comparing D-Pd versus Pd alone in this patient group.
He said the subcut formulation of daratumumab has similar efficacy and safety profiles as IV daratumumab but had the added benefit of significantly lower rates of infusion-related reactions and a shorter administration duration of five minutes.
Professor Dimopoulos, from the National and Kapodistrian University of Athens, said subcut dartumumab had recently been approved in North America, South America, Europe and Asia.
The study comprised 300 patients with RRMM from 12 European countries. Patients were mainly an elderly population (median age 68 yrs), about one-third had advanced stage disease at time of treatment and one-third had high risk cytogenetics.
Patients had received a median of two previous lines of therapy and entered into the study about 4.5 yrs after their myeloma diagnosis.
The study found a statistically significant and clinically meaningful difference in PFS in favour of D-PD over Pd alone. Overall, the median PFS was 12.4 months versus 6.9 months (HR 0.63, p=0.0018). The 12-month PFS rate was 52% versus 35%.
“Thus, the addition of subcut daratumumab to Pd improved PFS with a 37% reduction in the risk of progression or death.”
“This benefit was essentially seen across all subgroups of patients including younger and older patients, patients with different ISS disease staging, regardless of lines of prior therapy, regardless of cytogenetic risk and also in patients who were refractory to lenalidomide.”
In patients refractory to lenalidomide, PFS was 9.9 months v 6.5 months.
Professor Dimopoulos said the triplet of D-PD was superior to Pd in overall response rate (ORR), very good partial response (VGPR) rate, complete response (CR) rate and achievement of MRD-negative disease
“D-Pd achieved significantly deeper responses versus Pd alone including a >6 times higher ≥CR rate (25% v 4%) and a >4 times higher MRD negativity rate (9% v 2%).”
Adverse events were consistent with the known profiles of subcut daratumumab and Pd alone.
The most common serious adverse events were pneumonia (15% v 8%) and lower respiratory tract infections (12% v 9%) with a slightly increased risk probability in the D-Pd arm.
“TEAEs leading to treatment discontinuation were similar and low in both groups or patients (2% v 3%). The same was observed for AEs leading to death (7% v 7%).”
The incidence of second primary malignancy was low at 2% for each group.
Infusion-related reactions (IRR) were reported in 5% of D-PD patients; all of them were grade 1 or 2.
“The IRR rate was low and administration duration short, thus increasing convenience for patients and decreasing treatment burden,” Professor Dimopoulos said.
Commenting on the study for the limbic, Professor Andrew Spencer from Alfred Health and Melbourne Haematology, said the major advantage of the subcut formulation was that it enables treatment in the home.
“There is a lot of enthusiasm these days for home-based cancer care for quality of life issues and resource implications for hospitals if they can treat people in their homes versus sitting in a day ward.”
Professor Spencer said other drugs such as rituximab had moved to subcut in lymphoma and some of the bi-specific T-cell engagers which were given IV in the original trials were now being trialled as subcut.
“So there is a recognition that logistically it is easier if you can give treatment subcut rather than IV and there is some advantage in terms of toxicity in some cases as well.”
He said D-Pd was however a high cost combination treatment which might be challenging for the PBAC.
The APOLLO study was a collaboration between the European Myeloma Network and Janssen.