Sustained MRD-Negativity With Sc Daratumumab in Newly Diagnosed Multiple Myeloma

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Data from the PERSEUS trial supports use of daratumumab in combination with bortezomib, lenalidomide, and dexamethasone followed by daratumumab and lenalidomide maintenance as a new standard of care for patients with newly diagnosed multiple myeloma.

Findings from the phase 3 PERSEUS (NCT03710603) clinical trial show sustained MRD-negativity for patients with newly diagnosed (ND) multiple (MM) were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Conference. In an interview with the Pharmacy Times®, Paula Rodriguez-Ortero, MD, PhD, specialist in hematology and hemotherapy at the University of Navarra Clinic, shared her insights from the study and the measurable success of daratumumab as a front line treatment for NDMM.

Pharmacy Times: Why was subcutaneous daratumamab administration selected vs intravenous daratumamab, and are there specific benefits in relation to minimal residual disease (MRD) negativity rates?

Paula Rodriguez-Otero: Subcutaneous administration is now available, approved, and used worldwide in any daratumumab-based combination, also because the other agents that were used in the study—bortezomib, lenalidomide, and dexamethasone—were either oral or subcutaneous. So, the subcutaneous formulation of daratumumab made more sense in this setting. Regarding the MRD, the efficacy of IV and the subcutaneous is identical. There is no reason to believe that MRD will be different using the subcutaneous formulation or the IV.

Pharmacy Times: What are some of the challenges or successes of subcutaneous daratumamab in combination with standard-of-care treatment administration in relation to wait times, etc, and how were potential challenges addressed in the trial?

Rodriguez-Ortero: Subcutaneous formulation…is now widely used and has replaced the IV formulation of daratumumab across the different combinations and across the different countries. So, the subcutaneous formulation has several advantages. So, it will significantly reduce the chair time in the hospital, it is much more convenient for the patient, and it has a lower incidence of infusion related reactions. And so, it's probably a better way to deliver daratumumab as compared to the IV.

Pharmacy Times: What are some common adverse effects observed with this treatment, and what was the rate of these adverse effects for patients in this trial?

Rodriguez-Ortero: I am mostly covering the [MRD] rates. So, overall, what we can expect with daratumumab-based combination is a slightly higher incidence of infections and eventually also a higher incidence of neutropenia. But overall, the safety profile of the daratumumab-VRd in the study was expected and manageable with very few interruptions for the patients.

Pharmacy Times: What are some of the challenges for patients with multiple myeloma around the need for multiple transplants, and how might DARA SC in maintenance potentially help to address some of these challenges?

Rodriguez-Ortero: So, [MM] is difficult to cure. I will not say it’s an incurable disease, but definitely a difficult-to-cure disease and patients frequently face relapses. So, the way that we have improved the progression-free survival [PFS] and the duration of response, therefore improving survival, is by using a prolonged therapy both in the front-line setting with maintenance and in the relapse setting. So, in this study the combination of daratumumab plus lenalidomide in the maintenance part showed an improvement in the depth of response, in the rates of MRD negativity and sustained MRD negativity compared to the standard arm. At the end of the day, this led to an improvement in [PFS] and potentially a higher proportion of patients that may be potentially cured, because they have reached very deep and sustained MRD negativity rates.

Pharmacy Times: What are the key barriers preventing access to advanced immunotherapies and quadruple therapy regimens for multiple myeloma patients, and what strategies can be developed to ensure equitable treatment access for all patients?

Rodriguez-Ortero: One of the main challenges of treatment access is the price. For sure, these are expensive therapies, and definitely it’s much cheaper when you can cure a patient compared to using one treatment followed by another. So, I think that in the front line, we really need to use the best therapies available to increase the proportion of patients that may be eventually cured. And it definitely is the role of regulators and agencies to make this a reality for all of our patients, to make these treatments available and make the countries able to cover or pay for these expensive drugs.

Pharmacy Times: How might the application of daratumumab in combination therapies shape the future landscape of multiple myeloma treatment, and what potential challenges and opportunities do these developments present for clinical practice?

Rodriguez-Ortero: Daratumumab is already a very well-established drug in the treatment of [MM], both from front-line, transplant-eligible, transplant-ineligible, all the way through to different relapse combinations. And nowadays, it's been developed in combination with novel immunotherapy such as bispecific antibodies. Daratumumab has several advantages: it is very well tolerated, it is easy to deliver combines very well with a different standard of care seen in [MM], and it definitely improves both depth and duration of response and [PFS]. So, it's one of the pillars of [MM] therapy and it's one of the drugs that should be used as early as possible.

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