Subcutaneous Daratumumab Could Mark First Smoldering Myeloma Treatment

With a positive opinion from the European Committee for Medicinal Products for Human Use (CHMP) and a vote in favor of the indication from the FDA’s Oncology Drugs Advisory Committee (ODAC), subcutaneous daratumumab (Darzalex Faspro) is looking at approvals on the horizon in the US and in Europe for use in high-risk smoldering multiple myeloma, which could possibly preclude the development of multiple myeloma in patients on the therapy.^1,2

Janssen-Cilag International NV announced via a news release on June 20 that the CHMP, a part of the European Medicines Agency (EMA), has formally recommended the approval of subcutaneous daratumumab in adults with smoldering multiple myeloma.¹ This follows a 6-2 ODAC vote in favor of the indication announced May 20 by Johnson & Johnson.²

Treatment is not yet recommended for smoldering myeloma, meaning that subcutaneous daratumumab, if approved, stands to become the first treatment available for the asymptomatic disease and potentially prevent multiple myeloma and the associated end-organ damage.

“Therapies like subcutaneous daratumumab offer a promising proactive approach to delaying or even preventing the progression of smoldering myeloma to active multiple myeloma,” said Heather Wenberg, BSN, RN, OCN, regional director of nursing at the American Oncology Network, said in an email interview with Oncology Nursing News. “Early intervention may not only extend patients' lives but also help them avoid the need for more intensive treatments down the road.”

AQUILA Data Behind the Recommendation

Recommendations from both agencies were based on phase 3 data from the AQUILA trial (NCT03301220) presented at the 2024 American Society of Hematology Annual Meeting and Exposition and published simultaneously in the New England Journal of Medicine.^1,2 The results of this analysis were later presented at the 50th Annual Oncology Nursing Society Congress.

Treatment with subcutaneous daratumumab reduced the risk of progression or death compared to active monitoring by 51% (HR, 0.49; 95% CI, 0.36-0.67; P < .001).³ Additionally, median progression-free survival (PFS) was not reached in the daratumumab arm, compared with 41.5 months with active monitoring.

At 60 months, overall survival rates were 93.0% and 86.9% in the daratumumab and active monitoring arms, respectively, ultimately reducing the risk of death 48% (HR, 0.52; 95% CI, 0.27-0.98). Daratumumab also generated an overall response rate of 63.4% compared with 2.0% for active monitoring (P < .001).

Treatment-emergent adverse events (TEAEs) grade 3 or higher were reported in 40.4% of patients receiving daratumumab, vs 30.1% of the active monitoring arm. The most common TEAE was hypertension (5.7% vs 4.6%, respectively), and the most common serious TEAE was pneumonia (3.6% vs 0.5%, respectively).

Subcutaneous Daratumumab: A Nurse Favorite in Multiple Myeloma

The use of subcutaneous daratumumab is already supported by the FDA in multiple myeloma. The treatment was approved in combination with bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone, together referred to as Darzalex Faspro-VRd, on July 30, 2024.⁴

The treatment is known to be well tolerated and reduce chair time for patients with multiple myeloma dramatically due to its subcutaneous administration.

“The chance of infusion reaction is much lower [with subcutaneous daratumumab]. You still do see the occasional reaction to patients who are receiving it in their first cycle,” advised Chad Robertson, PA-C, a senior physician assistant at the Mount Sinai Multiple Myeloma Center of Excellence, on the use of the regimen in multiple myeloma in an interview with Oncology Nursing News. “Fewer chances of reaction make for happier patients.”

Because the treatment is so well tolerated, it is frequently used across patient subgroups.

“We use it with just about anybody; this is our go-to,” said Robertson. “We use it in induction. It’s used in maintenance a lot of the time, so there isn’t a specific population [that benefits more].”

Looking Forward: What Will This Mean for Oncology Nurses?

With relatively few AEs associated with the treatment, subcutaneous daratumumab could provide a smoother transition for patients experiencing an asymptomatic cancer diagnosis.

“As these strategies gain traction, nurses will play a pivotal role in patient education—shifting the focus from managing symptoms to helping patients understand the rationale behind treating an asymptomatic condition,” added Wenberg. “Nurses will also guide patients in recognizing and managing potential [adverse] effects.”

In multiple myeloma, the drug is associated with injection-site reactions (usually occurring at the first injection and often preventable with premedication), hypersensitivities, neutropenia, thrombocytopenia, embryo-fetal toxicities, and interference with serological testing. Nurses should provide patients with smoldering multiple myeloma education on the potential for these AEs to occur before and during treatment.

While the subcutaneous administration benefits patients by reducing chair time, the administration is more intensive for nurses and may take more of a toll physically and in terms of time.

As emphasized by Sylwia Zielinska, RN, of Vanderbilt University Medical Center in Nashville, Tennessee, in a written guide on the use of subcutaneous daratumumab in multiple myeloma, the injection time can last up to 5 minutes, and nurses are encouraged to sit down to prevent back pain. Wenberg echoed the need for strategic coordination for nurses.

“The simplicity and efficiency of administering subcutaneous daratumumab make it ideal to this proactive model,” added Wenberg. “However, it will require a streamlined workflow that supports fast, seamless clinic visits, while continuing to support a high quality of life for these patients.”

Check out our Rx Road Map on subcutaneous daratumumab for multiple myeloma, featuring insights from top experts!

References

1. DARZALEX (daratumumab) receives the first positive CHMP opinion for patients with high-risk smouldering multiple myeloma. Johnson & Johnson. News release. June 20, 2025. Accessed June 20, 2025. https://www.jnj.com/media-center/press-releases/darzalex-daratumumab-receives-the-first-positive-chmp-opinion-for-patients-with-high-risk-smouldering-multiple-myeloma
2. U.S. FDA Oncologic Drugs Advisory Committee votes in favor of the benefit-risk profile of DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) for high-risk smoldering multiple myeloma. Johnson & Johnson. News release. May 20, 2025. Accessed June 20, 2025. https://www.jnj.com/media-center/press-releases/u-s-fda-oncologic-drugs-advisory-committee-votes-in-favor-of-the-benefit-risk-profile-of-darzalex-faspro-daratumumab-and-hyaluronidase-fihj-for-high-risk-smoldering-multiple-myeloma
3. Dimopoulos MA, Voorhees PM, Schjesvold F, et al. Phase 3 Randomized study of daratumumab monotherapy versus active monitoring in patients with high-risk smoldering multiple myeloma: primary results of the Aquila study. Blood. 2024;144(suppl 1):773. doi:10.1182/blood-2024-201057
4. FDA approves daratumumab and hyaluronidase-fihj with bortezomib, lenalidomide, and dexamethasone for multiple myeloma. FDA. July 30, 2024. Accessed July 30, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-daratumumab-and-hyaluronidase-fihj-bortezomib-lenalidomide-and-dexamethasone-multiple