Drug Update · Hematology

FDA Approves Daratumumab for NDMM Ineligible for ASCT: 52.3% MRD

July 14, 2026

Approval date

01/27/2026

Indication

Newly diagnosed multiple myeloma in adults ineligible for autologous stem cell transplant

MRD negativity rate

52.3% vs 34.8% (DARZALEX FASPRO-VRd vs VRd) (p=0.0005)

PFS

Reduced risk of progression or death by 40% (HR 0.60; 95% CI 0.41-0.88)

Recommended dose

1,800 mg/30,000 units subcutaneously

Clinical Perspective

This affects hematologists, oncologists, and advanced practice providers treating adults with newly diagnosed multiple myeloma who are ineligible for ASCT, as DARZALEX FASPRO is now FDA-approved for use with bortezomib, lenalidomide, and dexamethasone in that population ^[2]. The CEPHEUS data support higher MRD negativity rates (52.3% versus 34.8%) and a reduction in the risk of progression or death (HR 0.60; 95% CI 0.41-0.88) when DARZALEX FASPRO is added to VRd, per the trial report ^[2]. How best to sequence DARZALEX FASPRO with other combination regimens and with later-line agents such as BCMA-directed therapies in real-world practice remains an open question?

Dr. Shruti Pandey · Hematology

The FDA approved daratumumab and hyaluronidase-fihj (DARZALEX FASPRO) in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for adult patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT) on January 27, 2026 based on the CEPHEUS trial, which showed an overall minimal residual disease (MRD) negativity rate of 52.3% with DARZALEX FASPRO-VRd versus 34.8% with VRd (p-value 0.0005) and a progression-free survival benefit (HR 0.60; 95% CI 0.41-0.88) ^[2]. Clinicians should consult current prescribing information for complete dosing guidance.

Clinical Context

Daratumumab is a CD38-directed cytolytic monoclonal antibody formulated with hyaluronidase for subcutaneous administration as DARZALEX FASPRO; the product combines daratumumab and hyaluronidase to enable subcutaneous delivery ^[3]. The FDA approval on January 27, 2026 covers use of DARZALEX FASPRO in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed multiple myeloma patients who are ineligible for ASCT ^[2]^[3]. The DARZALEX FASPRO label also lists multiple combination and monotherapy indications across disease settings, including combinations with carfilzomib and dexamethasone and with lenalidomide and dexamethasone in other settings, reflecting its broad development program ^[3]. Separately, elranatamab (ELREXFIO) is a bispecific BCMA-directed CD3 T-cell engager indicated for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody; that indication is an accelerated approval based on response rate and durability of response ^[1].

Key Findings

The CEPHEUS trial showed DARZALEX FASPRO-VRd achieved an MRD negativity rate of 52.3% versus 34.8% with VRd in newly diagnosed multiple myeloma patients ineligible for ASCT (p-value 0.0005) in CEPHEUS (NCT03652064) ^[2].
DARZALEX FASPRO-VRd reduced the risk of progression or death by 40% versus VRd (HR 0.60; 95% CI 0.41-0.88) per independent review committee assessment in CEPHEUS ^[2].
The FDA–recommended DARZALEX FASPRO dose is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously over approximately 3 to 5 minutes; full prescribing information contains the complete schedule and combination dosing instructions ^[2]^[3]. Clinicians should consult current prescribing information for complete dosing guidance.

Safety & Tolerability

Hypersensitivity and other administration reactions (DARZALEX FASPRO) ^[2].
Infections (DARZALEX FASPRO) ^[2].
Neutropenia (DARZALEX FASPRO) ^[2].
Thrombocytopenia (DARZALEX FASPRO) ^[2].
Embryo-fetal toxicity (DARZALEX FASPRO) ^[2].
Interference with cross-matching and red blood cell antibody screening (DARZALEX FASPRO) ^[2].
Cardiac toxicity in patients with light chain (AL) amyloidosis (DARZALEX FASPRO) ^[2].
Cytokine release syndrome (CRS) (ELREXFIO) ^[1].
Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS) (ELREXFIO) ^[1].
Infections (ELREXFIO) ^[1].
Neutropenia (ELREXFIO) ^[1].
Hepatotoxicity, including elevated ALT, AST, and bilirubin (ELREXFIO) ^[1].
Common adverse reactions with ELREXFIO reported at incidence ≥20% include CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia ^[1].
The most common Grade 3 to 4 laboratory abnormalities with ELREXFIO reported at ≥30% were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets ^[1].

Study Design

CEPHEUS (NCT03652064) was an open-label, randomized, active-controlled trial enrolling 395 patients with newly diagnosed multiple myeloma who were ineligible for or refused ASCT; 197 patients were randomized to DARZALEX FASPRO-VRd and 198 to VRd ^[2]. The co-primary efficacy measures reported were overall MRD negativity rate and progression-free survival (PFS) by independent review committee based on International Myeloma Working Group response criteria; MRD negativity was 52.3% versus 34.8% (p=0.0005), and PFS HR was 0.60 (95% CI 0.41-0.88) ^[2]. The FDA approval announcement is dated January 27, 2026 ^[2].

FAQ

Q1 What is DARZALEX FASPRO approved for?

DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) is approved in combination with bortezomib, lenalidomide, and dexamethasone (VRd) for adults with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). The approval was announced by the FDA on January 27, 2026 and is supported by CEPHEUS trial data showing higher MRD negativity and improved PFS with the addition of DARZALEX FASPRO to VRd.

Q2 How does daratumumab work?

Daratumumab is an IgG1Îº human monoclonal antibody that binds to CD38 on plasma cells and mediates tumor cell kill through direct apoptosis and immune-mediated mechanisms including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and antibody-dependent cellular phagocytosis. In DARZALEX FASPRO the antibody is combined with hyaluronidase to enable subcutaneous administration.

Q3 What is the recommended dose of DARZALEX FASPRO?

The recommended DARZALEX FASPRO dose is 1,800 mg/30,000 units (1,800 mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously over approximately 3 to 5 minutes according to the dosing schedule in the prescribing information; specific schedules differ when used as monotherapy or in combination regimens and across induction, consolidation, and maintenance phases. Clinicians should consult current prescribing information for complete dosing guidance.

Q4 What are the side effects of DARZALEX FASPRO?

The DARZALEX FASPRO prescribing information and FDA approval notice list hypersensitivity and other administration reactions, infections, neutropenia, thrombocytopenia, embryo-fetal toxicity, interference with red blood cell antibody testing and cross-matching, and cardiac toxicity in patients with light chain (AL) amyloidosis as labeled safety concerns. In addition, the ELREXFIO label (elranatamab) notes boxed warnings for cytokine release syndrome and neurologic toxicity including ICANS, and lists infections, neutropenia, hepatotoxicity, and common adverse reactions (including CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, pyrexia) for that agent; these sources should be consulted for full safety and laboratory monitoring details. Clinicians should consult current prescribing information for complete dosing guidance.

FDA Approves Daratumumab for NDMM Ineligible for ASCT: 52.3% MRD

FDA Approves Daratumumab for NDMM Ineligible for ASCT: 52.3% MRD

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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