Minimal residual disease has been a major topic of discussion during the IMS 2024 Annual Meeting.
New data from the phase 3 AURIGA study (NCT03901963) show that the addition of subcutaneous daratumumab (Darzalex; Johnson & Johnson) to lenalidomide (Revlimid; Bristol Myers Squibb) as maintenance therapy resulted in a higher conversion rate to minimal residual disease (MRD) in patients with transplant-eligible newly-diagnosed multiple myeloma (NDMM) who were MRD positive and anti-CD38 naïve after autologous stem cell transplant (ASCT).1
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MRD negativity has been a major topic of discussion during the International Myeloma Society (IMS) 2024 Annual Meeting, happening September 25 through 29 in Rio de Janeiro, Brazil. In April, the FDA’s Oncology Drugs Advisory Committee (ODAC) voted unanimously to allow MRD negativity as a surrogate end point for accelerated approvals,2 which experts hope will expedite patient access to treatments.
“[The ODAC] decision was made to support accelerated approval of new drugs, and I think this also highlights the importance of the AURIGA MRD negative comparative data, which support that MRD negativity improves [progression-free survival] and deeper responses,” said Ashraf Badros, MBCHB, presenter of the AURIGA data at IMS 2024, in an interview with Pharmacy Times. “And if the FDA accepts that as a surrogate end point, that will help a lot of patients get access to drugs quicker than waiting for PFS and overall survival, which, as you know, takes a long time to reach in myeloma these days.”
The AURIGA trial reinforces the value of MRD as a surrogate end point. The trial enrolled eligible patients aged 18 to 79 years of age with NDMM who had very good partial response or better and were MRD positive following ASCT, were anti-CD38–naïve, received 4 or more induction cycles, and were enrolled within 12 months of the start of induction therapy and 6 months of ASCT. Participants were stratified by cytogenic risk and randomized 1:1 to receive 28-day cycles of lenalidomide maintenance therapy with or without subcutaneous daratumumab for up to 36 cycles or until disease progression, unacceptable toxicity, or withdrawal. The primary end point was MRD-negative conversion rate by 12 months from start of maintenance therapy.1
Trial Name: A Study of Daratumumab Plus Lenalidomide Versus Lenalidomide Alone as Maintenance Treatment in Participants With Newly Diagnosed Multiple Myeloma Who Are Minimal Residual Disease Positive After Frontline Autologous Stem Cell Transplant (AURIGA)
ClinicalTrials.gov ID: NCT03901963
Sponsor: Janssen Research & Development LLC
Completion Date (Estimated): May 2026
Induction/consolidation with ASCT and lenalidomide maintenance is standard of care for transplant-eligible patients with NDMM. Daratumumab is a human anti-CD38 monoclonal antibody with FDA-approval for induction/consolidation treatment of this patient population, but to date, no randomized trials have directly compared daratumumab-based therapy to standard-of-care lenalidomide maintenance therapy.1
According to the AURIGA study findings, 200 patients were randomized, with 99 in the daratumumab-lenalidomide (DR) arm and 101 in the lenalidomide (R)-only arm. The demographic characteristics were well-balanced with a median age of 63 years in the DR group and 62 years in the R group; and 23.9% and 23.5% of patients, respectively, with stage 3 disease. At diagnosis, 23.9% of DR patients and 16.9% of R patients had high cytogenetic risk. Study participants received a median of 5 induction cycles in both groups prior to study entry.1
By 12 months, the MRD-negativity conversion rate was 50.5% for the DR group and 18.8% in the R group, with a consistent benefit favoring DR across all relevant subgroups. At a median follow-up of 32.3 months, overall MRD-negativity rate was 60.6% for the DR arm and 27.7% for the R arm.1
Furthermore, complete response or better favored the DR (75.8% vs 61.4%) as did progression-free survival with an estimated 30-month rate of 82.7% for DR and 66.4% for R. Patients in the DR arm received a median of 33 maintenance cycles, whereas patients in the R arm received a median of 21.6 cycles; 88.5% and 78.6%, respectively, completed 12 cycles.1
Grade 3/4 treatment-emergent adverse events occurred in more patients in the DR arm than the R arm, at 74% and 67.3%, respectively. Importantly, Badros said he believes this reflects the longer time on study for those in the DR group.
“[DR patients] stayed on the study for 30 months vs 20 months for the Revlimid arm, and we believe that staying on the study longer increased reporting risk, so you report more side effects if you take the treatment longer,” Badros explained. “And I think that’s what we’re observing here.”
Importantly, Badros said the AURIGA results should be taken in the context of other trial results, including the GRIFFIN and PERSEUS trials.
“All of [these trials] are supporting the addition of daratumumab at induction, and now we have data to support using it in maintenance,” Badros said. “I think the message here is the addition of daratumumab to lenalidomide led to deeper responses.”
