Daratumumab Boosts Depth and Durability of Response After ASCT, Offering Clear Guidance for Pharmacist Counseling

New insights from the AURIGA study (NCT03901963) highlight how adding daratumumab to lenalidomide (D-R) after autologous stem cell transplant (ASCT) nearly doubles minimal residual disease (MRD)-negativity conversion rates at both 10^-5 and 10^-6 thresholds, an achievement that strengthens confidence in this combination for deeper, more durable responses.

According to hematologist-oncologist Alfred Chung, MD, with UCSF Health, the marked rise in both initial and sustained MRD negativity has meaningful implications for pharmacists, from shaping expectations about potentially longer periods of disease control to informing monitoring strategies for early signs of recurrence. As researchers work toward less invasive MRD assessment methods, these findings underscore the value of D-R maintenance in delaying progression and guiding individualized patient conversations around long-term therapy planning.

Q: How do the MRD-negativity conversion rates at both thresholds in AURIGA influence your confidence in adding daratumumab to lenalidomide for post-ASCT maintenance?

Alfred Chund, MD: Yeah, so in both the 10^-5 and 10^-6 thresholds for MRD, the addition of daratumumab to lenalidomide led to higher rates of MRD negativity, almost doubling those rates. And in patients who are MRD positive after autologous stem cell transplant, the addition, I think, increases the odds that patients get into the MRD negativity. And we know from other studies that MRD negativity portends a better prognostic factor overall, so it increases the confidence that patients can get to these deeper responses.

Q: From a pharmacist’s standpoint, what are the key implications of the significantly higher sustained >12-month MRD-negative rates with D-R, and how might this affect patient counseling or expectations around long-term disease control?

Chung: Yeah, so we know that sustained MRD negativity is probably an even better marker for long term outcomes than just a 1-time MRD negativity status. So, the addition of daratumumab in this study significantly increase the rates of sustained MRD negativity, especially at the 10^-6 threshold. So, these are patients who can have, you know, long term responses, and daratumumab and lenalidomide increase those odds as well. And so by having increased sustained MRD negativity, that means that patients may stay on the therapy longer.

In the AURIGA study, it was for 36 cycles, and patients who attain a good response may be able to stay on that line of therapy and have a delay in progression overall. So, from a pharmacy standpoint, this may mean that the patient may be able to stay on the therapy longer and continue to do well if they achieve sustained MRD negativity. Also, there are some practices where people stop the therapy when people are in sustained MRD negativity, so that is also an option to discuss, and it may depend a little bit on patient characteristics and disease factors

Q: Given the differences in MRD-positive recurrence between the D-R and R arms, how should pharmacists think about monitoring strategies or early identification of functional high-risk patients during maintenance therapy?

Chung: Yeah, so these MRD statuses are obtained at bone marrow biopsies that are done, so it depends on the provider to do a bone marrow biopsy to get the MRD status. And so…it's being done at different times among patients in the real world practice, and we are trying to develop better ways of looking at MRD in the peripheral blood so patients don't have to get bone marrow biopsies as frequently. But when bone marrow biopsies are done, and for patients who get sequential MRD analyses, the development of MRD recurrence may be kind of an early marker of disease recurrence. And so, the patients who have this going into MRD negativity and then developing MRD recurrence, those patients are at higher risk. If we do see that in practice, that may be kind of a sign that the patient may need a treatment change in the near future—and how long that is may depend on the patient. And in the AURIGA study, in the data that we are presenting, the addition of daratumumab to lenalidomide led to lower rates of these recurrences, especially at the 10^-6 level, and that was predominantly in the standard risk group. But also, the high-risk group did see a kind of a little bit of a reduction compared to the low-risk group. So, in general, it seems that the addition of daratumumab to lenalidomide may kind of slow down the recurrence of MRD.