This article is sponsored by Johnson & Johnson. Rafat Abonour, MD, Hematologist and Oncologist, University of Miami, is a paid consultant for Johnson & Johnson and must present information in accordance with U.S. Food & Drug Administration (FDA) requirements.
The content discusses DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj), which is indicated in combination with other regimens or as monotherapy in adult patients with multiple myeloma. DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulations. See the complete Indications and Important Safety Information below.
Why Early, Informed Treatment Decisions Matter
Over the years, the treatment landscape for newly diagnosed multiple myeloma (NDMM) has evolved significantly, yet the clinical challenge remains: How can healthcare providers (HCPs) select the right regimen for NDMM patients to delay disease progression and achieve treatment goals?
With over 36,000 new multiple myeloma cases expected in the United States this year, early and effective intervention can be key.1 For providers, frontline treatment choice is critical because each additional line of therapy following an individual’s relapse is associated with lower response rates, shorter treatment duration and treatment-free intervals, and increased rates of toxicities and comorbidities.2 Therefore, evidence-based frontline selection is essential to maintaining therapeutic benefits and treatment responses over time, including delaying disease progression.2
A Foundational Frontline Therapy
As the most prescribed monoclonal antibody in multiple myeloma, DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) has helped redefine the way HCPs approach treating their adult patients who are newly diagnosed with multiple myeloma.3 DARZALEX FASPRO® is the first and only subcutaneous anti-CD38 monoclonal antibody injection that can provide rapid administration in approximately 3-5 minutes, though it’s important to keep in mind this does not account for all aspects of administration or treatment.4
DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation. Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®.
Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®. Please see below for the full Important Safety Information for
DARZALEX FASPRO®.
Despite recent progress, multiple myeloma remains a highly variable and incurable disease because patients will unfortunately experience relapses after initial treatment.5 Innovative and proven frontline treatments remain critical for patients when they are first diagnosed with multiple myeloma, and healthcare providers are continuing to seek effective options for them.2
A New Regimen for Transplant-Ineligible Patients with NDMM
In January 2026, the U.S. Food and Drug Administration (FDA) approved
DARZALEX FASPRO® in combination with bortezomib, lenalidomide, and dexamethasone (DVRd) in adult patients with NDMM who are ineligible for autologous stem cell transplant (ASCT).4 This approval marks the third indication for DARZALEX FASPRO® in transplant ineligible (TIE) patients with NDMM and reinforces the impact this product continues to have for this patient population.4
This approval was based on findings from the Phase 3 CEPHEUS study, a randomized, open-label, multicenter trial that evaluated the efficacy and safety of DVRd compared to bortezomib, lenalidomide, and dexamethasone (VRd) in 395 NDMM patients who were TIE or for whom transplant was not planned as the initial therapy (transplant deferred).6 The study met its primary endpoint, finding that at a median follow-up of 22 months, the overall minimal residual disease (MRD)-negativity rate at 10-5 (no cancer cells detected within 100,000 bone marrow cells) was 52.3% with DVRd vs 34.8% with VRd (P<0.0005).4 The effectiveness of DVRd has not been established in patients who refused ASCT as initial therapy. This new DVRd indication is now the first and only FDA-approved regimen based on a study using MRD-negativity as a primary endpoint.
“Although the last decade has seen strides in the multiple myeloma landscape, there is a continued need for innovation in the frontline setting,” said Rafat Abonour, MD, Hematologist and Oncologist, University of Miami. “DVRd increased the depth and durability of responses for transplant-ineligible patients compared to VRd, underscoring the potential of this regimen to become a new standard of care in newly diagnosed multiple myeloma.”
Major secondary endpoints included complete response (CR) or better rate, progression-free survival (PFS), and sustained MRD-negativity rate at 10-5, demonstrating that at a median follow-up of 39 months:
- A significant reduction in the risk of disease progression or death by 40% (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41-0.88; P<0.0078) for DVRd vs VRd4
- The proportion of patients achieving sustained MRD-negativity of at least 12 months was 42.6% for DVRd vs 25.3% for VRd (P<0.0003)4
At a median follow-up of nearly 5 years (59 months):
- A CR or better rate of 81.2% with DVRd vs 61.6% with VRd4
The overall safety results of DVRd were consistent with the types of adverse reactions seen for DARZALEX FASPRO® and VRd.
“Minimal residual disease testing, though not widely used in clinical practice for multiple myeloma, has become a standard and helpful tool in clinical trials for evaluating depth of response, understanding disease risk, and potentially predicting outcomes across disease settings,” said Dr. Abonour. “The data supporting this new quadruplet regimen provides evidence for DVRd at this stage of disease for patients who aren’t eligible for transplant.”
Versatility Across Newly Diagnosed Patient Populations
Now approved for transplant-ineligible patients, DVRd is the only anti-CD38 antibody-based regimen approved for all patients with NDMM, regardless of transplant eligibility.4 DVRd is also approved for induction and consolidation treatment of newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplant. Daratumumab-based regimens are standard-of-care treatments across patients with multiple myeloma, with more than 748,000 patients treated worldwide across indications.
“Multiple myeloma is a complex and highly varied disease, which reinforces the need for continued clinical evidence that will help care teams make the best treatment choice for their patients. Daratumumab-based regimens have proven to be consistently effective frontline therapies for physicians seeking to achieve the goal of delaying disease progression for multiple myeloma patients who are newly diagnosed,’’ said Dr. Abonour. “With these continued clinical advancements in multiple myeloma, we now have another robust treatment regimen that has the potential to improve patient outcomes from the start of their treatment journey.”
To learn more about the clinical data for DARZALEX FASPRO® visit www.darzalexhcp.com.
INDICATIONS
DARZALEX® (daratumumab) is indicated for the treatment of adult patients with multiple myeloma:
- In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
- In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
- In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
- In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
- In combination with pomalidomide and dexamethasone in patients who have received at least two prior therapies including lenalidomide and a proteasome inhibitor (PI)
- As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent
DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:
- In combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
- In combination with bortezomib, lenalidomide, and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- In combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
- In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
- In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)
- In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
- In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
- As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent
IMPORTANT SAFETY INFORMATION
DARZALEX® AND DARZALEX FASPRO®: CONTRAINDICATIONS
DARZALEX® and DARZALEX FASPRO® are contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase (for DARZALEX FASPRO®), or any of the components of the formulations.
WARNINGS AND PRECAUTIONS
DARZALEX®: Infusion-Related Reactions
DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37% of patients with the Week 1 (16 mg/kg) infusion, 2% with the Week 2 infusion, and cumulatively 6% with subsequent infusions. Less than 1% of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma.
Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension, and blurred vision.
When DARZALEX® dosing was interrupted in the setting of autologous stem cell transplant (ASCT) (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11% for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1%) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42%, with 36% of patients experiencing infusion-related reactions on Day 1 of Week 1, 4% on Day 2 of Week 1, and 8% with subsequent infusions.
Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion.
To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease.
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®.
DARZALEX FASPRO®: Hypersensitivity and Other Administration Reactions
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO®. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO®.
Systemic Reactions
In a pooled safety population of 1446 patients with multiple myeloma (N=1235) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or as part of a combination therapy, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3%, Grade 3: 0.8%, Grade 4: 0.1%).
In all patients (N=1639), systemic administration-related reactions occurred in 7% of patients with the first injection, 0.5% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 283 systemic administration-related reactions that occurred in 135 patients, 240 (85%) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.
Severe reactions included hypoxia, dyspnea, hypertension, tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.
Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen, and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO®. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO® depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO® and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO®.
Local Reactions
In this pooled safety population of 1446 patients with multiple myeloma (N=1253) or light chain amyloidosis (N=193), injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 1.1%. The most frequent (>1%) injection-site reactions were injection site erythema and injection site rash. In patients with high-risk smoldering multiple myeloma (N=193), injection-site reactions occurred in 28% of patients, including Grade 2 reactions in 3%. These local reactions occurred a median of 6 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO®. Monitor for local reactions and consider symptomatic management.
DARZALEX FASPRO®: Infections
DARZALEX FASPRO® can cause serious, life-threatening, or fatal infections. In patients who received DARZALEX FASPRO® in a pooled safety population including patients with smoldering multiple myeloma and light chain (AL) amyloidosis (N=1639), serious infections, including opportunistic infections, occurred in 24% of patients, Grade 3 or 4 infections occurred in 22%, and fatal infections occurred in 2.5%. The most common type of serious infection reported was pneumonia (8.5%).
Monitor patients for signs and symptoms of infection prior to and during treatment with DARZALEX FASPRO® and treat appropriately. Administer prophylactic antimicrobials according to guidelines.
DARZALEX® and DARZALEX FASPRO®: Neutropenia and Thrombocytopenia
DARZALEX® and DARZALEX FASPRO® may increase neutropenia and thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX® or DARZALEX FASPRO® until recovery of neutrophils or for recovery of platelets.
In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed.
DARZALEX® and DARZALEX FASPRO®: Interference With Serological Testing
Daratumumab binds to CD38 on red blood cells (RBCs) and results in a positive indirect antiglobulin test (indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX® and DARZALEX FASPRO®. Type and screen patients prior to starting DARZALEX® and DARZALEX FASPRO®.
DARZALEX® and DARZALEX FASPRO®: Interference With Determination of Complete Response
Daratumumab is a human immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) assays used for the clinical monitoring of endogenous M-protein. This interference can impact the determination of complete response and of disease progression in some patients with IgG kappa myeloma protein.
DARZALEX® and DARZALEX FASPRO®: Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX® and DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. DARZALEX® and DARZALEX FASPRO® may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX® or DARZALEX FASPRO® and for 3 months after the last dose.
The combination of DARZALEX® or DARZALEX FASPRO® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy.
DARZALEX®: ADVERSE REACTIONS
The most frequently reported adverse reactions (incidence ≥20%) with DARZALEX® were upper respiratory infection, neutropenia, infusion-related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40%) with DARZALEX® are neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia.
DARZALEX FASPRO®: ADVERSE REACTIONS
In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, sleep disorder, headache, rash, renal impairment, motor dysfunction, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, musculoskeletal pain, decreased appetite, urinary tract infection, abdominal pain, upper respiratory tract infection, peripheral neuropathy, peripheral sensory neuropathy, constipation, pneumonia, edema, dizziness, bruising, and COVID-19.
The most common hematologic laboratory abnormalities (≥40%) with DARZALEX FASPRO® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.
Please click here to read full Prescribing Information for DARZALEX®.
Please click here to read full Prescribing Information for DARZALEX FASPRO®.
cp-248517v7
© Johnson & Johnson and its affiliates 2026 05/26 cp-515089v1
###
1 American Cancer Society. Key Statistics About Multiple Myeloma. Accessed February 1, 2026. https://www.cancer.org/cancer/types/multiple-myeloma/about/key-statistics.html
2 Fonseca R, Usmani SZ, Mehra M, et al. Frontline treatment patterns and attrition rates by subsequent lines of therapy in patients with newly diagnosed multiple myeloma. BMC Cancer. 2020;20(1). doi:10.1186/s12885-020-07503-y
3 Data on file. SD-216728. Janssen Biotech, Inc.
4 DARZALEX FASPRO® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
5 Raedler LA. Darzalex (Daratumumab): first anti-CD38 monoclonal antibody approved for patients with relapsed multiple myeloma. Am Health Drug Benefits. 2016; 9:70-73. Accessed February 1, 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC5013856/
6 Usmani S, Facon T, Hungria V, et al. Daratumumab plus bortezomib, lenalidomide and dexamethasone for transplant- ineligible or transplant-deferred newly diagnosed multiple myeloma: the randomized phase 3 CEPHEUS trial. Nat Med. 2025;31:1195–1202. https://doi.org/10.1038/s41591-024-03485-7