Daratumumab (Darzalex) in Multiple Myeloma: Competitive Landscape

Daratumumab, sold as Darzalex, is an anti-CD38 monoclonal antibody and one of the most consequential drugs in multiple myeloma. It is a central example of how a single agent can reshape a disease’s standard regimens.

Mechanism at a glance

Daratumumab binds CD38, a protein highly expressed on myeloma cells, and kills them through several immune mechanisms, including antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Infusion-related reactions are common with the first dose, and the antibody can interfere with blood-bank cross-matching, which clinics must plan for.

How it earned its position

Daratumumab was added to many established combinations, including those with immunomodulatory drugs, proteasome inhibitors and steroids, across newly diagnosed and relapsed disease. A subcutaneous formulation with hyaluronidase shortened administration compared with the intravenous form and extended the franchise’s reach. It is also approved in earlier disease: for high-risk smoldering myeloma in the EU in July 2025 and in the US in November 2025.

What competes with it

• Other CD38 antibodies, such as isatuximab.
• BCMA- and GPRC5D-directed bispecifics, which are moving into earlier lines.
• CAR-T cell therapies, with their own manufacturing and access challenges.
• Quadruplet versus triplet strategies, as sponsors test where adding a fourth drug pays off.

What CI teams should track

1. Minimal residual disease (MRD) as an endpoint, and how regulators treat it.
2. Sequencing: what comes after a CD38-based regimen, and whether prior exposure changes response to later therapies.
3. Community versus academic uptake of T-cell redirecting therapies.
4. Subcutaneous and off-the-shelf options that lower the burden of care.

Hematologic malignancies move quickly around the major conferences, so December’s ASH meeting is usually the key catalyst.

Recent developments

Updated October 8, 2026. Items are drawn from company announcements, regulators and trade press; links go to the sources.

• Jul 15, 2026: Genmab announced worldwide Darzalex net trade sales of $4,207 million for Q2 2026 (US $2,435 million; rest of world $1,772 million). (1stOncology)
• Jul 9, 2026: FDA approved subcutaneous isatuximab (Sarclisa Escena), adding a subcutaneous option to the other CD38 antibody. In IRAKLIA the response rate was 71.1% subcutaneous vs 70.5% IV, with systemic administration reactions of 1.5% vs 25%. (CancerNetwork)
• Jun 13, 2026: MonumenTAL-3 (EHA plenary, NEJM): talquetamab plus daratumumab, with or without pomalidomide, beat DPd in 864 patients. PFS HR was 0.28 (with pomalidomide) and 0.33 (without), and 24-month PFS was 81.3% and 77.6% vs 51.2%. (OncLive)
• Apr 29, 2026: Pfizer announced that MagnetisMM-5 met its PFS primary endpoint: elranatamab monotherapy vs daratumumab-pomalidomide-dexamethasone in 497 patients. No numbers have been disclosed yet. (International Myeloma Foundation)
• Mar 5, 2026: FDA approved Tecvayli (teclistamab) plus Darzalex Faspro after at least one prior line (MajesTEC-3; 587 patients). Median PFS was not reached vs 18.1 months in the control arm. Tecvayli carries a boxed warning for cytokine release syndrome and neurotoxicity. (CURE)
• Feb 23, 2026: FDA accepted the application for anito-cel, a BCMA CAR-T therapy, in fourth-line relapsed or refractory myeloma, with a PDUFA date of December 23, 2026. Gilead announced the same day that it would acquire Arcellx, at an implied equity value of $7.8 billion including a contingent payment. (Kite/Gilead)
• Jan 27, 2026: FDA approved Darzalex Faspro with VRd for transplant-ineligible newly diagnosed myeloma (CEPHEUS). MRD negativity was 52.3% vs 34.8% at a median 22 months, and the PFS HR was 0.60 at a median 39 months. (J&J)
• Dec 2025: At ASH, MajesTEC-3 showed teclistamab plus daratumumab beating standard daratumumab-based regimens after 1-3 prior lines: PFS HR 0.17 and overall survival HR 0.46. (Clinical Trials Arena)
• Nov 6, 2025: FDA approved Darzalex Faspro for high-risk smoldering myeloma, the first approved therapy in that setting (AQUILA: PFS HR 0.49; five-year progression-free 63.1% vs 40.7%). The EU approval came July 23, 2025. (J&J)

Upcoming catalysts

• Dec 12-15, 2026: ASH Annual Meeting, New Orleans; likely venue for fuller MagnetisMM-5 data and further bispecific and CAR-T combinations.
• Dec 23, 2026: FDA action date for anito-cel in fourth-line relapsed or refractory myeloma (company-stated).

Bottom line

Daratumumab is a durable backbone, but the center of gravity in myeloma is moving toward T-cell redirecting therapies in earlier lines. Tracking how those therapies are combined with, or replace, CD38-based regimens is the most important competitive question. Recent trials suggest combination more than replacement: the experimental arms of both MajesTEC-3 and MonumenTAL-3 include daratumumab.

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This article is for informational and competitive-intelligence purposes only and is not medical advice. Approvals, labels and trial results change; verify details against current prescribing information and primary sources.