Maintenance treatment with Darzalex (daratumumab) and Revlimid (lenalidomide) resulted in superior outcomes compared with standard-of-care Revlimid alone following autologous stem cell transplantation in patients with newly diagnosed multiple myeloma, according to data from the phase 3 AURIGA study.
The AURIGA study evaluated treatment responses among 200 patients with newly diagnosed multiple myeloma who experienced very good or better partial responses, were MRD-positive and anti-CD38-naïve following transplant. By 12 months from the start of maintenance therapy, 50.5% of the 99 patients in the Revlimid and Darzalex arm had achieved minimal residual disease (MRD) negativity, versus 18.8% of the 101 patients in the standalone Revlimid arm, researchers reported.
At a median follow-up of 32.3 months, 60.6% of patients in the combination arm had achieved MRD negativity versus 27.7% of patients who received Revlimid alone, while complete response rates or better were 75.8% and 61.4%, respectively. The rate of sustained MRD negativity lasting at least six months in the combination arm was approximately 2.5 times that of patients in the Revlimid arm, at 35.4% versus 13.9%.
Glossary
Autologous stem cell transplantation: when a patient’s healthy blood-forming cells are collected and stored before treatment then given back to the patient after treatment.
Minimal residual disease: a small number of cancer cells that remain in the body after treatment.
Progression-free survival: the time that a patient lives without their disease spreading or worsening.
Cytopenias: low levels of red blood cells, white blood cells or platelets.
Myelodysplastic syndrome: cancers where immature blood cells in the bone marrow do not mature or become healthy blood cells.
Peripheral sensory neuropathy: damage to the nerves outside of the brain and spinal cord.
Researchers further noted that 30-month progression-free survival rates were 82.7% for patients in the combination arm and 66.4% for patients who only received Revlimid maintenance therapy.
“These results support the addition of [Darzalex] not only to induction/consolidation, but also to [standard-of-care Revlimid] maintenance for these patients,” said Dr. Ashraf Z. Badros and fellow researchers in their findings published in Blood. “Future studies should continue to assess the implementation of [Darzalex]-based maintenance in other patient populations and determine the optimal point of treatment initiation and cessation.”
Badros is a professor of medicine with the University of Maryland Medical System in Baltimore.
Darzalex, according to the National Cancer Institute, binds to the protein CD38 found on some types of immune cells and cancer cells, including myeloma cells, and may block CD38 and help the immune system kill cancer cells. Revlimid may help the immune system kill abnormal blood cells or cancer cells, according to the National Cancer Institute.
Safety Data and More Information on the AURIGA Study
Regarding safety, patients in the combination arm experienced higher rates of grade 3 (severe) and 4 (life-threatening) cytopenia’s (54.2% versus 46.9%) and infections (18.8% versus 13.3%) than patients who received Revlimid maintenance monotherapy.
Among the 194 patients who received at least one dose of study treatment — 96 patients in the combination arm, 98 in the Revlimid alone arm — treatment-related side effects of any grade were reported in 99% of patients in both groups, with grade 3 or 4 side effects occurring in 74% and 67.3% of patients, respectively. Serious side effects were reported among 30.2% and 22.4% of patients, with the most frequent being pneumonia at 4.2% and 4.1%, respectively.
Side effects resulted in treatment discontinuation for 14.6% and 8.2% of patients, most commonly due to myelodysplastic syndrome for the combination arm (2.1%) and peripheral sensory neuropathy for the Revlimid arm (2%). Fatal side effects were reported in two patients in the combination arm (one each due to COVID-19 pneumonia and Legionella pneumonia) and one patient in the Revlimid monotherapy arm, due to COVID-19 pneumonia.
“In the randomized, phase 3 AURIGA study, the addition of [Darzalex] to [Revlimid] maintenance resulted in a significantly higher MRD-negative conversion rate among transplant-eligible patients with [newly diagnosed multiple myeloma] who had [a very good partial response or better], were MRD-positive and were anti-CD38–naïve after [autologous stem cell transplantation], compared with [Revlimid] maintenance alone,” Badros and colleagues wrote. “This increase in MRD-negative conversion was clinically meaningful given that [Darzalex-Revlimid] maintenance trended toward improved [progression-free survival], higher overall MRD-negative conversion rates and deeper responses compared with [Revlimid] maintenance alone, with no unexpected safety concerns.”
Reference
“Daratumumab with lenalidomide as maintenance after transplant in newly diagnosed multiple myeloma: the AURIGA study” by Ashraf Badros, et al., Blood.
For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.
