Sponsored by Johnson & Johnson
Relapsed or refractory multiple myeloma (RRMM) is a challenging blood cancer that affects plasma cells in the bone marrow.1 This highly variable and complex disease results in relapse for nearly all patients at some point in time.1 The options become increasingly limited for these patients, with many experiencing reduced responsiveness to therapy over time and multiple lines of treatment failure.1 For this reason, a multidisciplinary care team is essential to achieving optimal patient outcomes. The therapeutic landscape for RRMM is also advancing rapidly, with a shift toward more immunotherapies, including bispecific antibodies–a class of treatments that redirect the patient’s own T cells to target malignant myeloma cells.2
Many cancer centers are working quickly and efficiently to incorporate bispecific treatment regimens into their clinical protocols. Multidisciplinary care teams work together to address patients’ disease symptoms and treatment-related adverse reactions, as well as psychosocial needs.3 These teams include hematologists, advanced practice providers (APPs), pharmacists, nurses, and supportive care specialists, who all work to help ensure optimal patient outcomes.4
In the case of bispecifics, these multidisciplinary care teams can help avoid more serious immune-related adverse reactions associated with this class of agents and provide education to patients and care partners about the importance of adverse reaction reporting.
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI. Initiate treatment with TECVAYLI step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI until CRS resolves or permanently discontinue based on severity.
Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious, life-threatening, or fatal reactions, can occur in patients receiving TECVAYLI. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI until neurologic toxicity resolves or permanently discontinue based on severity.
TECVAYLI is available only through a restricted program called the TECVAYLI and TALVEY® Risk Evaluation and Mitigation Strategy (REMS).
To gain insights into implementing care strategies for patients with RRMM in a community setting, Oncology Issues interviewed several members of a multidisciplinary team at Allegheny Health Network. Below is an overview of these team members and their roles and responsibilities.
Prerna Mewawalla, MD, Director of the Stem Cell Transplant and Cellular Therapy Program and Medical Director of Apheresis at Allegheny Health Network Cancer Institute, is a hematologist-oncologist specializing in plasma cell disorders, stem cell transplantation, and cellular therapy. Within the bispecific-based treatment workflow, she provides physician leadership for:
Sophia Marcinko, MPAS, PA-C, is responsible for:
Melissa Horneman, RN, is responsible for:
Samantha Maples, PharmD, BCOP, clinical pharmacy specialist supervisor for Hematology and Cellular Therapy, is responsible for:
In March 2026, the combination of Tecvayli® (teclistamab-cqyv) and Darzalex Faspro® (daratumumab and hyaluronidase-fihj), a treatment known as TEC-DARA SC, was approved by the Food and Drug Administration (FDA) for the treatment of adults with RRMM who have received at least one prior line of therapy, including a proteasome inhibitor and an immunomodulatory agent.5 Tecvayli in combination with Darzalex Faspro works to target myeloma cells in adult patients with RRMM who have received at least one prior line of therapy, including a proteasome inhibitor and immunomodulatory agent.5,6 Darzalex Faspro binds to CD38 on the surface of myeloma cells, as well as on certain other types of cells, such as red blood cells.6 Tecvayli binds to BCMA on the surface of myeloma cells and some healthy B-lineage cells, as well as to CD3 on the surface of T-cells.5 These two treatments together enable and enhance the immune-mediated lysis of myeloma cells.5,6
Warnings and Precautions include hepatotoxicity, infections, neutropenia, hypersensitivity and other administration reactions, and embryo-fetal toxicity.
Please read the full Important Safety Information for Tecvayli below, and click here to read the full Prescribing Information, including Boxed WARNING, for Tecvayli.
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.
See full Important Safety Information for Darzalex Faspro below, and click here to read full Prescribing Information for Darzalex Faspro.
The approval was based on data from the phase 3 MajesTEC-3 study, a randomized (1:1), multicenter, open-label study evaluating the safety and efficacy of Tecvayli plus Darzalex Faspro versus the investigator’s choice of daratumumab and dexamethasone with either pomalidomide or bortezomib in 587 patients with RRMM who received one to three prior lines of therapy, including a PI and lenalidomide.5 Patients who had received only one prior line of therapy must have been refractory to lenalidomide.5 Patients were excluded from the trial if they had disease refractory to a prior anti-CD38 monoclonal antibody therapy or had received any prior BCMA-directed therapy.5 For more information, see MajesTEC-3 Study Results.
The MajesTEC-3 study is part of the MajesTEC clinical program, which is exploring the potential of Tecvayli in combination with other agents. The primary endpoint of MajesTEC-3 was progression-free survival (PFS), and key secondary endpoints included overall survival (OS), complete response (CR) or better, overall response rate (ORR), minimal residual disease negativity, time to worsening symptoms, and additional secondary endpoints included safety.7
TEC-DARA SC demonstrated superior improvements in PFS and OS in patients with RRMM compared to investigator’s choice of either daratumumab and hyaluronidase-fihj, pomalidomide and dexamethasone (DPd) or daratumumab and hyaluronidase-fihj, bortezomib and dexamethasone (DVd) after a median follow-up of 34.5 months in patients with RRMM.5,7 The study showed an 83% reduction in the risk of disease progression or death compared to DPd or DVd (HR, 0.17; 95% CI: 0.12-0.23; P<0.0001). The estimated three-year PFS rate was 83.4% (95% CI: 78.2-87.4), for TEC-DARA SC (n=291), compared to 29.7% (95% CI: 23.6-36.0)compared to DPd or DVd (n=296). The study also showed 54% reduction in the risk of death with TEC-DARA SC compared to DPd or DVd (HR 0.46; 95% CI: 0.32-0.65; P<0.0001).5,7
At a median follow-up of 34.5 months, 81.8% (95% CI: 76.9-86.0) of patients who received TEC-DARA SC achieved a CR or better compared to 32.1% (95% CI: 26.8-37.7) with DPd or DVd; P<0.0001. Moreover, for TEC-DARA SC an ORR of 89% (95% CI, 84.8-92.4) was achieved, including a stringent complete response (sCR) in 77.3% of patients, CR in 4.5%, very good partial response (VGPR) in 4.8%, and partial response (PR) in 2.4% (95% CI, 70.0-80.1).5,7 For patients receiving DPd or DVd, an ORR of 75.3% (95% CI: 70.0-80.1) was achieved, including sCR in 23.3% of patients, CR in 8.8%, VGPR in 25%, and PR in 18.2%.5,7
Among patients who received TEC-DARA SC, the median exposure was 32.4 months, compared to median exposure of 16.1 months for those who received DPd or DVd.7 CRS occurred in 60.1% of patients who received the study combination, and all cases were Grade 1/2.7 ICANS occurred in 1.1% of patients–including one patient with Grade 4–with all events occurring during step-up dosing.8 The grade 4 event led the patient to cease use of Tecvayli while continuing to receive Darzalex Faspro.8 The median time to onset of ICANS was 2 days (range, 1 to 3) after the most recent dose, and the median duration of ICANS was 2 days (range, 1 to 2).7 Serious adverse reactions occurred in 70.7% of patients receiving TEC-DARA SC compared to 62.4% of patients who received DPd or DVd.7 Moreover, 2.5% of patients who received TEC-DARA SC experienced fatal adverse reactions, including sepsis (0.7%), pneumonia (0.4%), sudden death (0.4%), myocardial infarction (0.4%), enterovirus myocarditis (0.4%), and hemophagocytic lymphohistiocytosis (0.4%), as opposed to 3.8% of patients treated with DPd or DVd. 6% of patients permanently discontinued Tecvayli due to adverse reactions, including pneumonia (1.1%), diarrhea (0.7%), fatigue (0.7%), second primary malignancy (0.7%), upper respiratory tract infection (0.7%), and cough (0.7%).5,8
Due to the nature of treatment with Tecvayli and the potential for adverse reactions like CRS, including life-threatening or fatal reactions, and neurologic toxicity, including ICANS, which can be serious, life-threatening or fatal, Tecvayli has a Boxed Warning and is available only through a restricted program called the Tecvayli and Talvey Risk Evaluation and Mitigation Strategy (REMS). The goal of the REMS is to mitigate the risk of CRS and neurologic toxicity, including ICANS, by ensuring prescribers are aware of the importance of monitoring for the signs and symptoms of CRS and neurologic toxicity including ICANS in patients exposed to Tecvayli.5 Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after the first two doses of the “step-up dosing schedule.” Instruct patients to remain within proximity of a healthcare facility and monitor them daily for 48 hours after the first “treatment dose” of Tecvayli.5
Most community cancer centers have multidisciplinary teams that are experienced with complex chemotherapy regimens. “Community programs do not have to reinvent the model from scratch,” said Dr. Mewawalla. “They already manage complex oncology regimens every day. The key is to adapt those existing strengths into a bispecific-specific workflow: define who owns patient education, who monitors after dosing, who responds to fever or neurologic symptoms, and how quickly the patient can be evaluated if symptoms arise.” These providers can build on their existing knowledge to incorporate bispecifics into patient care, with a focus on understanding the management of potential adverse reactions such as CRS and neurotoxicity, including ICANS.
At Allegheny Health Network, the team considers a variety of clinical and logistical factors such as disease burden, frailty, comorbidities, baseline infection risk, care partner support to determine the most appropriate ways to support care and monitoring. The team educates, supports, and encourages community cancer centers to become REMS-certified where required, so they can build the infrastructure needed to offer bispecific-based ongoing treatments such as TEC-DARA SC closer to where patients live. “REMS certification is an important first step for any administering facility, but it is only one part of readiness,” said Prerna Mewawalla, MD. “Programs also need a defined process for patient selection, care partner education, post-dose monitoring, communication across sites, and rapid escalation if fever, neurologic symptoms, or other concerning symptoms develop. The goal is to make outpatient administration structured, deliberate, and reproducible for patients who meet appropriate criteria as they follow the approved dosing protocols.”
REMS-certified community sites mean patients do not have to keep making long trips for subsequent treatment doses—they can continue their treatment and follow-up visits in their own communities. The Allegheny Health Network team also recommends that these community cancer centers schedule patients’ appointments in advance and have a consistent day and time for subsequent treatments.
This team’s collective expertise was used to develop the following best practices for TEC-DARA SC initiation, proactive and reactive adverse reaction management, and provision of ongoing patient care.
Before initiating TEC-DARA SC, a comprehensive patient assessment should be completed to help ensure optimal outcomes and minimize potential complications. This baseline evaluation should include laboratory values such as complete blood count (CBC), liver function tests, renal function tests, and immunoglobulin levels to establish a starting point for monitoring during treatment. Additionally, cardiac and pulmonary assessments should be conducted as clinically appropriate to identify any pre-existing conditions that may impact treatment tolerability.
The care team should establish supportive protocols prior to treatment initiation, including selection of prophylactic antimicrobial agents tailored to individual patient risk factors and initiation of antiviral prophylaxis to prevent herpes zoster reactivation per the Tecvayli prescribing information. Premedication protocols should be implemented to minimize infusion-related reactions, with corticosteroids, histamine-1 receptor antagonists, and antipyretics administered 1 to 3 hours before each dose of the step-up dosing schedule to reduce the risk of CRS per the Tecvayli prescribing information. “Thorough patient and care partner education covering the expected treatment course, monitoring requirements, and symptoms requiring immediate medical attention are essential to help ensure informed engagement in the care process,” said Melissa Horneman, RN.
Treatment initiation with TEC-DARA SC requires careful attention to CRS risk through premedication and strict adherence to the step-up dosing schedule. Premedication such as histamine-1 antagonists, antipyretics, and corticosteroids, should be administered prior to each dose as outlined in pre-treatment protocols and the Tecvayli prescribing information.
Initial doses should be administered in a hospital or infusion center with full capability for adverse reaction management as specified in the Tecvayli full Prescribing Information. Sophia Marcinko, MPAS, PA-C, emphasizes, “Comprehensive patient monitoring during and after administration, along with clear communication protocols and established adverse event management plans, enables our team to respond swiftly and effectively to complications that may arise.”
Ongoing management of patients treated with TEC-DARA SC requires consistent laboratory monitoring, including complete blood count (CBC), comprehensive metabolic panel, and liver function tests, as well as neurologic assessments, to assess tolerability. Per the Tecvayli prescribing information, monitor immunoglobulin levels prior to and during treatment with Tecvayli and administer subcutaneous or intravenous immunoglobulin (IVIG) to maintain the serum levels above 400 mg/dL, and strict adherence to infection prophylaxis protocols must be maintained throughout treatment.
Regular symptom monitoring and patient-reported outcomes help guide clinical decision-making and ensure timely intervention when needed. Samantha Maples, PharmD, notes, “Systematic monitoring and dosing protocols are essential to optimize therapeutic outcomes while minimizing adverse effects. Following the initial treatment phase, dosing every four weeks coupled with treatment administration at community cancer centers can make TEC-DARA SC an accessible long-term treatment option.”
Despite the availability of TEC-DARA SC, significant barriers to access exist between academic and community cancer settings. Understanding and addressing these obstacles is essential to ensuring all eligible patients can receive this therapy regimen.
Transportation remains one of the biggest barriers to initiating TEC-DARA SC. Many patients are unable to travel long distances for treatment. Community cancer centers are key to ensuring that more patients have access to available therapies, following necessary inpatient processes.
TECVAYLI® (teclistamab-cqyv) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma:
WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME
Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI. Initiate treatment with TECVAYLI step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI until CRS resolves or permanently discontinue based on severity.
Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious, life-threatening, or fatal reactions, can occur in patients receiving TECVAYLI. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI until neurologic toxicity resolves or permanently discontinue based on severity.
TECVAYLI is available only through a restricted program called the TECVAYLI and TALVEY® Risk Evaluation and Mitigation Strategy (REMS).
Cytokine Release Syndrome - TECVAYLI can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions.
In the clinical trials (monotherapy and combination therapy; N=448), CRS occurred in 64% of patients who received TECVAYLI at the recommended dosage, with Grade 1 CRS occurring in 46% of patients, Grade 2 in 18%, and Grade 3 in 0.2%. Recurrent CRS occurred in 27% of patients. Most patients experienced CRS during the initial step-up dosing schedule (step-up dose 1 [37%], step-up dose 2 [32%], or the initial treatment dose [20%]). CRS first occurred following subsequent doses of TECVAYLI in 2.5% of patients. The median time to onset of CRS was 2 (range: 1 to 9) days after the most recent dose and the median duration of CRS was 2 (range: 1 to 22) days.
Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).
Initiate therapy according to TECVAYLI step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI accordingly.
At the first sign of CRS, immediately evaluate the patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold until CRS resolves or permanently discontinue TECVAYLI based on severity.
TECVAYLI is available only through a restricted program under a REMS.
Neurologic Toxicity including Immune Effector Cell-Associated Neurotoxicity Syndrome - TECVAYLI can cause serious, life-threatening, or fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS).
In the clinical trials (monotherapy and combination therapy trials; N=448), neurologic toxicity occurred in 60% of patients who received TECVAYLI at the recommended dosage, with Grade 3 or 4 neurologic toxicity in 6%. Neurologic toxicities reported in ≥5% of patients included headache (27%), sensory neuropathy (16%), motor dysfunction (15%), insomnia (12%), encephalopathy (11%), and dizziness (8%). Fatal neurologic toxicity occurred in 0.4% of patients, including Guillain-Barré syndrome and status epilepticus (one patient each).
In MajesTEC-1, ICANS was reported in 6% of patients who received TECVAYLI as monotherapy at the recommended dosage. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent TECVAYLI doses. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia.
In MajesTEC-3, ICANS was reported in 1.1% of patients who received the recommended TECVAYLI dosage in combination with daratumumab and hyaluronidase-fihj, including Grade 4 ICANS in 1 patient. All events of ICANS occurred during the step-up dosing schedule. The median time to onset of ICANS was 2 (range: 1 to 3) days after the most recent dose and the median duration of ICANS was 2 (range: 1 to 2) days. The clinical manifestations of ICANS reported were amnesia, encephalopathy and delirium.
The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.
Monitor patients for signs and symptoms of neurologic toxicity, including ICANS during TECVAYLI treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold until neurologic toxicity resolves or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines.
Due to the potential for neurologic toxicity, patients receiving TECVAYLI are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.
TECVAYLI is available only through a restricted program under a REMS.
TECVAYLI and TALVEY REMS - TECVAYLI is available only through a restricted program under a REMS called the TECVAYLI and TALVEY REMS because of the risks of CRS and neurologic toxicity, including ICANS.
Hepatotoxicity - TECVAYLI can cause hepatotoxicity, including fatalities. There was one fatal case of hepatic failure in MajesTEC-1. In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448) elevated aspartate aminotransferase (AST) occurred in 47% of patients, with Grade 3 or 4 elevations in 2.9%. Elevated alanine aminotransferase (ALT) occurred in 48% of patients, with Grade 3 or 4 elevations in 3.8%. Elevated total bilirubin occurred in 10% of patients with Grade 3 or 4 elevations in 0.7%. Liver enzyme elevation can occur with or without concurrent CRS.
Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.
Infections - TECVAYLI can cause severe, life-threatening, or fatal infections.
In MajesTEC-1 (N=165), in patients who received the recommended TECVAYLI dosage, serious infections, including opportunistic infections, occurred in 30% of patients, Grade 3 or 4 infections in 35% of patients, and fatal infections in 4.2% of patients.
In MajesTEC-3 (N=283), in patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj at the recommended dosage, serious infections, including opportunistic infections, occurred in 54% of patients, Grade 3 or Grade 4 infections in 54% of patients, and fatal infections in 4.6% of patients.
Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI and treat appropriately. Administer prophylactic antimicrobials according to current practice guidelines.
Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.
Monitor immunoglobulin levels prior to and during treatment with TECVAYLI and administer subcutaneous or intravenous immunoglobulin (IVIG) to maintain the serum levels >400 mg/dL.
Neutropenia - TECVAYLI can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448), decreased neutrophils occurred in 88% of patients, with Grade 3 or 4 decreased neutrophils in 70%. Febrile neutropenia occurred in 6% of patients.
Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines.
Monitor patients with neutropenia for signs of infection.
Withhold TECVAYLI based on severity.
Hypersensitivity and Other Administration Reactions - TECVAYLI can cause both systemic administration-related and local injection-site reactions.
Systemic Reactions - In patients who received the recommended TECVAYLI dosage in the clinical trials (monotherapy and combination therapy trials; N=448), 2.5% of patients experienced systemic-administration reactions, which included recurrent pyrexia and rash.
Local Reactions - In patients who received TECVAYLI at the recommended dosage in the clinical trials (monotherapy and combination therapy trials; N=448), injection-site reactions occurred in 37% of patients, with Grade 1 injection-site reactions in 29% and Grade 2 in 9%.
Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.
Embryo-Fetal Toxicity - Based on its mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant patient. Advise pregnant patients of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose.
The most common adverse reactions (≥20%) in patients who received TECVAYLI monotherapy were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common adverse reactions (≥20%) in patients who received TECVAYLI in combination with daratumumab and hyaluronidase-fihj were hypogammaglobulinemia, upper respiratory tract infection, CRS, cough, diarrhea, musculoskeletal pain, COVID-19, pneumonia, injection site reaction, fatigue, pyrexia, headache, nausea, gastroenteritis, and weight decreased.
The most common Grade 3 to 4 laboratory abnormalities (≥20%) with TECVAYLI (as monotherapy or in combination with daratumumab and hyaluronidase-fihj) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.
Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI.
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DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma:
DARZALEX FASPRO® as monotherapy is indicated for the treatment of adult patients with high-risk smoldering multiple myeloma.
DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.
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 patients with high-risk smoldering multiple myeloma (N=193), systemic administration-related reactions occurred in 17% of patients in AQUILA (Grade 2: 7%, Grade 3: 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.
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.
Neutropenia
Daratumumab may increase neutropenia 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 FASPRO® until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO®, higher rates of Grade 3-4 neutropenia were observed.
Thrombocytopenia
Daratumumab may increase thrombocytopenia induced by background therapy. Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO® until recovery of platelets.
Embryo-Fetal Toxicity
Based on the mechanism of action, DARZALEX FASPRO® can cause fetal harm when administered to a pregnant woman. 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 FASPRO® and for 3 months after the last dose.
The combination of DARZALEX FASPRO® with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.
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 FASPRO®. Type and screen patients prior to starting 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 DARZALEX FASPRO®-treated patients with IgG kappa myeloma protein.
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 adverse reactions (≥20%) in patients with high-risk smoldering multiple myeloma who received DARZALEX FASPRO® monotherapy are upper respiratory tract infection, musculoskeletal pain, fatigue, diarrhea, rash, sleep disorder, sensory neuropathy, and injection site reactions.
The most common hematology 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 FASPRO®.
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© Johnson & Johnson and its affiliates 2026 08/26
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