AURIGA Results Support Addition of Daratumumab in Maintenance Setting for Myeloma

In an interview with Pharmacy Times, Ashraf Badros, MBCHB, discussed new data from the AURIGA study presented at the International Myeloma Society 2024 Annual Meeting, happening September 25 through 29 in Rio de Janeiro, Brazil. The results support the addition of daratumumab to lenalidomide in the maintenance setting, Badros said.

Q: What new findings are being presented at IMS 2024 from the AURIGA study?

Ashraf Badros, MBCHB: The primary end point has been met, and if you look at the group that achieved MRD negativity, they also have higher CR rate. We have some deepening of the responses in patients. And I believe—I have to look at that, one second—the CR rate in the dara-Revlimid arm was 74.8% versus 61% in the Revlimid alone arm.

Q: What should pharmacists know about this treatment regimen?

Badros: I think the trial at this point shouldn't be taken by itself. I think there is enough data between 3 big trials, the GRIFFIN trials, the PERSEUS trial, and now the AURIGA trial, and all of them are supporting the addition of daratumumab at induction, and now we have data to support using it in maintenance. I think the message here is the addition of daratumumab to lenalidomide led to deeper responses. Remember that two-thirds of the patients on the trial were in a very good partial response, meaning they have very deep responses to start with. And if you look at the patients on VRd alone, they deepen the response, so about 66% versus 45% in the lenalidomide alone arm. So, there are clear benefits for adding daratumumab in this particular subset of patients, which is achieving really good response after transplant, having MRT positivity, they do have deeper responses. That's really the benefit of the trial.

I also can tell you that if patients will ask [what this means], I think the deep response, if we look at the follow-up on our trial, which was about 32 months PFS, favored daratumumab-Revlimid. I just want to say the trial was not powered to detect PFS benefit. But if we look at our trial at 32 months, PFS favored daratumumab-Revlimid, with 47% reduction in the risk of progression or death versus Revlimid alone. If we look at 30 months, the PFS rate was 82% for daratumumab-Revlimid and 66% for Revlimid alone. Again, all the indications are that deeper responses also translate into improvement of progression free survival, and this has been established in many trials in multiple myeloma, and definitely this trial supports that. And the other issue we have to mention, as well as PFS benefit, CR benefit was noted among patients who are high risk, meaning if you have high risk myeloma, being bad cytogenetics and the elderly population and the patients with advanced stage disease. So, the treatment was beneficial across subgroups.

Q: What adverse events were seen?

Badros: I just want to mention, before the take-home message, which is what you're asking me, I just want to say that the serious adverse events were reported in about 30% of the daratumumab-Revlimid arm and 22% in the Revlimid arm. The most common were cytopenia and neutropenia, and infections. This trial was done during the COVID-19 era, and almost a quarter of the patients developed COVID-19, but the severe infection was actually very few patients. I believe it was 1% in the daratumumab-Revlimid arm and 3% in the Revlimid alone arm. [Furthermore], 14% in the daratumumab-Revlimid arm discontinued treatment due to side effects versus 8% in the Revlimid arm, so it's a little bit more side effects. But you need to remember [that] patients that received daratumumab-Revlimid stayed in the study longer. They 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. And I think that's what we are observing here. Patients stayed longer on the treatment, and that's why we report more side effects.

Q: If viewers get one key takeaway from the research, what should it be?

Badros: It is definitely a supportive trial. I wouldn't call this a conclusive trial for the effect of daratumumab in the maintenance setting. There are some trials being conducted—I cannot remember the name of the trial, it has one of those fancy names. So, the trial is randomizing 1400 patients between daratumumab and lenalidomide vs lenalidomide alone. And then after 2 years of maintenance, they do a second randomization. If you achieve MRD negativity, they try to decide, do you need the treatment or not. So, there is a second randomization to stop treatment if you are MRT negative or continue treatment. And this trial would be a definitive trial for the role of daratumumab with lenalidomide in the maintenance setting. Our results really support the addition of daratumumab. We know it's very effective in the induction consolidation as established standard of care, but now it is also supported in addition to lenalidomide maintenance for use. And I think everybody can take that decision individually, depending on the risk of the patient and the patient’s wishes and if they want to receive 1 or 2 drugs, but the data support deepening responses for that.

The data also add to a very important point, which as you are probably aware, that the FDA Oncology Drug Advisory Committee, which is the ODAC, voted in favor of using MRD testing as an early surrogate endpoint in multiple myeloma trials. That 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 PFS and deeper responses. And if the FDA accepts that as a surrogate endpoint, that will help a lot of patients get access to drugs quicker than waiting for PFS and overall survival, which, as you know, takes long time to reach in myeloma these days.