When to Consider Adding Daratumumab
- Data presented at the 2024 Society of Hematology Oncology (SOHO) Annual Conference highlighted the benefits of adding daratumumab (brand name Darzalex) to the maintenance plan for multiple myeloma (MM) patients.
- The addition of daratumumab to lenalidomide maintenance demonstrated a clear efficacy benefit in converting MRD-positive patients to MRD-negative status.
- “About 50% of the patients were able to achieve this MRD-negative conversion, whereas people with just lenalidomide, about 18% of those patients achieved that MRD-negative conversion,” Dr. Laahn Foster, a hematologist oncologist at the University of Virginia Cancer Center, tells SurvivorNet Connect.
- While lenalidomide maintenance has long been a standard, incorporating daratumumab could be considered—particularly for high-risk patients or those failing to achieve MRD negativity after frontline therapy.
Data presented at the 2024 Society of Hematology Oncology (SOHO) Annual Conference highlighted the benefits of adding daratumumab (brand name Darzalex) to the maintenance plan for multiple myeloma (MM) patients.
SurvivorNet Connect discussed these findings with Dr. Laahn Foster, a hematologist oncologist specializing in treating patients with plasma cell disorders at the University of Virginia Cancer Center.
She explained that for transplant-eligible patients with newly diagnosed multiple myeloma, the standard of care (SoC) treatment approach has traditionally involved an intensive therapeutic sequence: induction therapy, high-dose therapy and autologous stem cell transplantation (ASCT), consolidation therapy, and maintenance with lenalidomide (brand Revlimid).
“Currently daratumumab is used with three other drugs (Velcade, Revlimid and Dexamethasone), a four drug combination. Those patients typically go into transplant and after transplant, right now, the standard of care has been basically with lenalidomide [Revlimid] alone,” Dr. Foster explains.
“The point about this study is to see if there’s any additional benefit with adding daratumumab to lenalidomide maintenance.”
About the AURIGA Trial
AURIGA is the first randomized trial specifically comparing daratumumab plus lenalidomide maintenance therapy to lenalidomide maintenance alone in newly diagnosed multiple myeloma patients who were anti-CD38 naïve and MRD-positive after ASCT.
The trial enrolled 200 patients between the ages of 18 and 79, each of whom had previously received at least four cycles of induction therapy and achieved at least a very good partial response before undergoing ASCT. Following transplantation, all patients underwent minimal residual disease (MRD) assessment. Those who remained MRD-positive were randomized to receive either lenalidomide alone (n=101) or lenalidomide plus daratumumab (n=99).
Treatment was continued for up to 36 cycles (or until disease progression, unacceptable toxicity, or patient withdrawal), with the primary endpoint being MRD-negative conversion within 12 months. Key secondary endpoints included PFS as well as safety and tolerability profiles.
Efficacy Results: MRD-Negative Conversion and PFS
The addition of daratumumab to lenalidomide maintenance demonstrated a clear efficacy benefit in converting MRD-positive patients to MRD-negative status.
“About 50% of the patients were able to achieve this MRD-negative conversion, whereas people with just lenalidomide, about 18% of those patients achieved that MRD-negative conversion,” Dr. Foster explains.
“One of the cool things about the study is that we looked at the different subgroups that might be affected, who would benefit the most? Is it just standard risk patients or is it patients that have high risk features? And across all the different subgroups, whether they were standard risk or different subsets of high risk with different cytogenetic abnormalities, all patients seem to benefit from the addition of daratumumab with lenalidomide maintenance.”
MRD-Negative Conversion Rates
By Age: Patients under 65 receiving lenalidomide plus daratumumab achieved a 49.2% MRD-negative rate compared to 19.7% in the lenalidomide-alone arm (Odds Ratio [OR]: 3.95). Similarly, in patients 65 years or older, the MRD-negative rates were 52.6% versus 17.5% (OR: 5.24) in favor of lenalidomide plus daratumumab.
By Race: Among Black patients, the MRD-negative rate was 60.0% with lenalidomide plus daratumumab versus 16.7% with lenalidomide-alone (OR: 7.50). White patients also saw improvements (46.3% vs. 20.6%, OR: 3.32). Although sample sizes may limit definitive conclusions, these data suggest that the addition of daratumumab can benefit various racial groups and may be particularly impactful for Black patients.
By Disease Characteristics (ISS Stage and Cytogenetic Risk): ISS Stage III patients receiving lenalidomide plus daratumumab saw a notably high MRD-negative rate of 65.2% versus 13.0% in the lenalidomide-alone group (OR: 12.50). For those with high-risk cytogenetics—often a group that does not derive full benefit from standard therapies—the MRD-negative conversion rate was 43.8% with lenalidomide plus daratumumab compared to just 13.3% with R (OR: 5.06).
Progression-Free Survival (PFS)
Improved MRD-negativity rates translated into a meaningful PFS advantage for the lenalidomide plus daratumumab arm. At a median follow-up of 32.3 months, the addition of daratumumab improved PFS across multiple subgroups:
By Age: The hazard ratio (HR) for PFS was 0.51 in patients under 65 and 0.71 for those aged 65 or older, favoring D-R in both age groups.
By Race: For Black patients, the HR was 0.66, while White patients had an HR of 0.56 in favor of D-R. These results underscore the broad applicability of the benefit.
By ISS Stage III: Patients with advanced disease derived marked benefit (HR: 0.26), highlighting that even those with more aggressive disease biology may gain significant advantages from lenalidomide plus daratumumab maintenance.
Dr. Foster stresses that older patients benefited from lenalidomide plus daratumumab without a disproportionate increase in toxicity, and that the combination showed a clear PFS benefit even in high-risk cytogenetic subgroups.
Additionally, while there were no major efficacy differences by race, minority populations such as Black patients might derive particular benefit from lenalidomide plus daratumumab maintenance.
Implications for Clinical Practice & Guidelines
The AURIGA study results could inform future maintenance therapy guidelines for transplant-eligible NDMM patients who remain MRD-positive after ASCT and have not received a CD38 antibody as part of their induction therapy.
While lenalidomide maintenance has long been a standard, incorporating daratumumab could be considered—particularly for high-risk patients or those failing to achieve MRD negativity after frontline therapy.
Experts highlight that the results “could significantly impact current maintenance therapy guidelines” and position Lenalidomide plus Daratumumab as a potentially preferred maintenance option for certain patients. It is important to note that these findings apply primarily to patients who have not been previously exposed to a CD38 antibody.