Daratumumab (brand name Darzalex) is a targeted monoclonal antibody that binds to CD38, a protein that is present on the surface of multiple myeloma cells and certain other types of cells. Many of the presentations at ASH 2021 highlighted exciting information about daratumumab and its use in newly diagnosed and relapsed/refractory multiple myeloma patients. 

Daratumumab could soon be a potential treatment option for patients with high-risk monoclonal gammopathy of undetermined significance (MGUS) or low-risk smoldering multiple myeloma (SMM).

Dr. Omar Nadeem and his Dana Farber Cancer Institute colleagues presented the results of a phase II, single-arm study which examined patients with high-risk MGUS or low-risk SMM who may benefit from early treatment with daratumumab.  The study looks at whether early intervention with daratumumab in patients with these precursor conditions would lead to the elimination of the tumor clone, resulting in the prevention of progression to multiple myeloma. Patients enrolled in this study met eligibility for either high-risk MGUS or low-risk SMM as follows:

High-risk MGUS is defined as <10% bone marrow plasma cells and <3g/dL M protein and at least 2 of the following 3 high-risk criteria:

• Abnormal serum free light chain ratio of <0.26 or > 1.6
• M protein > or = 1.5g/dL
• Non-IgG M protein

Low-risk SMM is defined by one of the following 3 criteria:

• M protein > or = 3g/dL
• > or = 10% bone marrow plasma cells
• Serum free light chain ratio of <0.125 or >8

The primary objective of the study is to determine the percentage of patients who achieve very good partial response (VGPR) or greater after 20 cycles of daratumumab. Secondary objectives included duration of response, safety, and rates of minimal residual disease negativity in very good partial response or greater patients.

The study included 42 patients with a median age of 60 (range 38-76), with 22 males and 20 females. The majority of patients were classified as low-risk SMM (88.1%) and the remaining patients had high-risk MGUS (11.9%).  Nineteen (19%) of patients had abnormal cytogenetics.

Study Results

A total of 41 patients started treatment and are included in the toxicity results. Grade 3 toxicities were rare and only experienced in 5 of the 41 patients. They included diarrhea (2%), flu-like symptoms (2%), headache (2%), and hypertension (5%).

The most common side effects of any grade included fatigue (51%), cough (46%), nasal congestion (44%), headache (34%), hypertension (27%) nausea (32%), and leukopenia (32%).  Importantly, no patients have discontinued therapy due to toxicity.

Minimal response or better was observed in 82.9% of patients (34/41) and partial response or better was observed in 51.2% of patients (21/41).  Median overall survival and progression-free survival have not been reached and no patients have progressed to multiple myeloma

Conclusion

The conclusion of the research is that:

• Daratumumab is well tolerated among patients with high-risk MGUS or low-risk SMM with minimal toxicity
• Early treatment in this precursor patient population appears promising
• Longer follow-up is required to define the role of single-agent daratumumab in preventing progression to multiple myeloma, avoiding more toxic interventions in this low-risk patient population

To learn more about daratumumab, check out the “Know Your Therapy” unit from HealthTree University.  There is a course all about Darzalex and Darzalex Faspro. More than 300 online lessons are designed to educate and empower myeloma patients to be their own best advocate.

Videos can be viewed on HealthTree University or on YouTube.