In an interview with Pharmacy Times®, Larry Anderson, MD, PhD, professor in the department of internal medicine at UT Southwestern Medical Center in Texas, discussed the AURIGA study, which evaluated daratumumab plus lenalidomide versus lenalidomide alone as maintenance therapy for newly diagnosed multiple myeloma patients who were MRD positive after transplant. These findings were shared at the 22nd annual International Myeloma Society (IMS) meeting and exposition in Toronto, Canada, which showed significantly higher MRD negative conversion rates, improved progression-free survival, and no increase in grade 3 or 4 toxicities with the combination therapy. These updated results highlight the value of adding daratumumab to lenalidomide in extending disease control and maintaining a favorable safety profile.
Pharmacy Times: Can you start by introducing yourself?
Larry Anderson, MD, PhD: Yes, I’m Dr. Larry Anderson, Professor and Director of the Myeloma Program at UT Southwestern Medical Center in Dallas, Texas.
Pharmacy Times: What was the rationale behind evaluating subcutaneous daratumumab plus lenalidomide versus lenalidomide alone in the post-transplant maintenance setting?
Anderson: Many studies have shown that the addition of a CD38 antibody like daratumumab to other myeloma therapies, including lenalidomide and IMiD, can improve outcomes, especially in the frontline setting. This study looked at extending that into the maintenance setting after transplant for those who were MRD positive after their transplant.
Pharmacy Times: What updated efficacy results stood out in the AURIGA study, and how might they influence current standards of care?
Anderson: This study looked at the addition of Dara to lenalidomide and showed that the MRD negative conversion rates at this 24-month update were significantly more than doubled at both the 10⁻⁵ threshold and 10⁻⁶ threshold. The 6-month sustained MRD negativity was doubled, and the 12-month sustained MRD negativity was quadrupled compared to Revlimid alone.
Pharmacy Times: What were the key safety findings, and what adverse events should pharmacists be most attentive to when managing patients on this combination?
Anderson: Most of the adverse events with the addition of a CD38 antibody like daratumumab involve potential infusion or injection reactions, especially with the first dose. In this study, patients had not received CD38 therapy frontline, so they didn’t start it until their maintenance therapy. They had to go through the usual progression: weekly for two months, every other week for four months, and then once monthly for maintenance. With that first shot, most people are observed for a while afterward to watch for reactions. Blood counts need to be checked before each dose to ensure neutropenia and other issues are not contraindications, and patients must be carefully monitored for infections while on anti-CD38 therapy. Fortunately, in the AURIGA study, the addition of subcutaneous Dara to lenalidomide did not significantly increase the rate of grade 3 and 4 treatment-emergent adverse events.
Pharmacy Times: Is there anything you would like to add?
Anderson: I had the pleasure of presenting the updated safety and efficacy results of the randomized phase 3 AURIGA study of daratumumab plus lenalidomide versus lenalidomide alone as maintenance therapy for newly diagnosed myeloma patients who were MRD positive after autologous stem cell transplant.
This study enrolled patients who had not received CD38 therapy as part of their frontline treatment. They were at least VGPR or better for their response going into the trial and MRD positive at the 10⁻⁵ threshold. Patients were randomized 1:1 to either daratumumab subcutaneous plus oral lenalidomide (DR) or lenalidomide alone (R). They were stratified based on high-risk cytogenetics. Patients had received a median of five cycles of induction therapy; over 80% had received at least two cycles of bortezomib and lenalidomide induction, and 70% were in VGPR at study enrollment.
MRD testing was done by ClonoSEQ molecular testing on the bone marrow at 12, 18, 24, and 36 months. Previously, the 12-month MRD negative conversion rate, which was the primary endpoint, showed more than doubling with DR. This study focuses on the 24-month update of MRD testing and shows that patient characteristics were well balanced between the two cohorts regardless of age, stage, or race. There was a slight imbalance favoring the R cohort, with an increase in 17p deletion and high-risk cytogenetics in the DR subgroup.
Despite this, there was improvement in MRD negative conversion among all subgroups regardless of race, stage, age, or cytogenetic risk. Patients on DR therapy stayed on treatment longer, with more completing at least 24 cycles compared to R alone. There was no increased risk of grade 3 or 4 toxicity in the DR cohort, nor an increased risk of discontinuation due to therapy. In fact, discontinuation was lower.
With a median follow-up of 40.3 months, progression-free survival favored DR therapy compared to R, with a hazard ratio of 0.55, representing a 45% reduction in the risk of progression or death. The median progression-free survival has not yet been reached for the DR cohort compared to 47 months for the R cohort. At 36 months, progression-free survival was 78.6% for DR versus 61.4% for R. Overall survival data were immature, but there was a trend toward increased survival with DR.
There were no new safety concerns with this combination. In conclusion, DR maintenance compared to R maintenance for at least 24 cycles led to significantly increased MRD negative conversion, more than doubling the 6-month sustained negativity at the 10⁻⁵ threshold and nearly quadrupling the 12-month sustained negativity. There was a 45% reduction in risk of progression or death, with a 36-month progression-free survival rate of 76.8% for DR. The safety profile was maintained, and there was a trend toward improved overall survival. These updated efficacy and safety data from the AURIGA study continue to demonstrate the value of adding subcutaneous daratumumab to lenalidomide as maintenance in patients with newly diagnosed myeloma who are MRD positive after autologous stem cell transplant.