Daratumumab (DARZALEX), the first CD38-targeting biologic approved for multiple myeloma, has transformed the treatment landscape and established itself as a cornerstone therapy across multiple lines of care. Developed through a global licensing and development agreement between Genmab and Janssen Biotech, a Johnson & Johnson company, DARZALEX has become a standard of care in multiple myeloma, consistently demonstrating superior efficacy and a favorable safety profile across frontline and relapsed/refractory settings. The therapy has significantly outperformed competing anti-myeloma agents, including EMPLICITI, and remains Johnson & Johnson’s leading oncology product. 

In January 2026, the US FDA approved daratumumab and hyaluronidase (DARZALEX FASPRO) in combination with bortezomib, lenalidomide, and dexamethasone (D-VRd) for adults with NDMM who are ineligible for autologous stem cell transplantation, based on positive results from this Phase III CEPHEUS trial. With this approval, D-VRd became the only anti-CD38 antibody-based regimen approved for newly diagnosed multiple myeloma patients regardless of transplant eligibility, further strengthening DARZALEX’s position in the frontline treatment landscape.

At ASCO, data from the Phase III CEPHEUS trial showed that, 

Efficacy:

• Overall MRD negativity rate at 10⁻⁵ was 61.1% with DVRd vs. 40.0% with VRd.

• Sustained MRD-negativity ≥12 months: 49.3% vs. 29.0% (OR: 2.40; p = 0.0005).

• Sustained MRD-negativity ≥24 months: 44.4% vs. 23.4% (OR: 2.62; p = 0.0002).

• The ≥CR rate was 80.6% with DVRd vs. 61.4% with VRd.

• Median PFS not reached with DVRd vs. 50.2 months with VRd.

• 72-month PFS rate: 59.3% with DVRd vs. 38.3% with VRd.

• Overall survival favored DVRd over VRd, with further improvement observed after censoring for COVID-19 impact. 

Safety: 

• Progressive disease-related deaths: Lower with DVRd (5.6%) vs. VRd (12.0%).

• Treatment discontinuations due to TEAEs: Lower with DVRd (9.7%) compared with VRd (23.2%).

• Grade 3/4 TEAEs: Higher with DVRd (93.8%) vs. VRd (88.7%), but no new safety signals were observed.

• Second primary malignancies: Comparable between arms (13.9% vs. 14.1%).

KOL insights

“The CEPHEUS findings reinforce the role of quadruplet therapy in standard-risk transplant-ineligible multiple myeloma patients, while underscoring the need for more effective therapeutic strategies for patients with high-risk cytogenetic features, for whom the benefits of treatment intensification appear less pronounced.” – Expert Opinion

“Anti-CD38–based quadruplet regimens are generally considered a preferred treatment approach for transplant-ineligible multiple myeloma patients who are not frail and can tolerate intensive combination therapy.”– Expert Opinion

Conclusion-

According to DelveInsight in 2025, there were 30,347 symptomatic incident cases of multiple myeloma in the US. The multiple myeloma treatment landscape continues to evolve rapidly, with increasing adoption of anti-CD38–based combination regimens reshaping frontline care. The treatment landscape for multiple myeloma has expanded significantly with multiple drug classes targeting distinct disease pathways. Key therapies include immunomodulatory drugs (IMiDs) such as Lenalidomide (REVLIMID) and Pomalidomide (POMALYST), anti-CD38 monoclonal antibodies including Daratumumab (DARZALEX) and Isatuximab (SARCLISA), SLAMF7-targeting antibodies such as Elotuzumab (EMPLICITI), and proteasome inhibitors including Bortezomib (VELCADE), Carfilzomib (KYPROLIS), and Ixazomib (NINLARO). While these therapies have significantly improved survival outcomes over the past decade, disease relapse remains common after initial treatment. DARZALEX (daratumumab) has established itself as a key backbone therapy in multiple myeloma due to its ability to enhance depth of response and prolong disease control when combined with standard regimens.

Overall, the results further strengthen DARZALEX’s position as a foundational agent in frontline multiple myeloma therapy, supporting its continued expansion across earlier treatment settings.