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Safety Profile

Safety profile you may be familiar with managing1-3

Adverse reactions (≥10%) in patients who received ZENBEXUS + Dd in EXCALIBER-RRMM1

ADVERSE REACTION ZENBEXUS + Dd
(N=204)		 DVd
(N=204)
All grades (%) Grade 3–4 (%) All grades (%) Grade 3–4 (%)
Infections and infestations        
Upper respiratory tract infection* 54† 6 52 6
Pneumonia‡ 34 25 17 10
COVID-19§ 23 3.9 16 2.9
General disorders and administration site conditions        
Fatigue§ 36 3.4 33 2.5
Edema§ 17 0.5 24 1
Pyrexia 14 1 15 1
Musculoskeletal and connective tissue disorders        
Musculoskeletal pain§ 35 1.5 33 2.9
Bone pain§ 11 1 13 0.5
Gastrointestinal disorders        
Diarrhea§ 33 4.9 36 6
Constipation 20 0 22 1
Nausea 14 0.5 6 0
Nervous system disorders        
Motor dysfunction∥ 26 1.5 17 2.5
Sensory neuropathy 19 4.4 53 6
Dizziness§ 11 0 9 0.5
Skin and subcutaneous tissue disorders        
Rash§ 26 1 15 0.5
Psychiatric disorders        
Sleep disorder# 25 2.9 28 1.5
Immune system disorders        
Hypogammaglobulinemia** 24 1 12 0.5
Respiratory, thoracic, and mediastinal disorders        
Cough§ 18 0.5 14 0.5
Dyspnea§ 10 0 9 1
Renal and urinary disorders        
Renal impairment§ 11 3.4 8 3.9
Vascular disorders        
Hemorrhage†† 10 1.5 9 2

Select laboratory abnormalities (≥30%) that worsened from baseline‡‡
in patients who received ZENBEXUS in EXCALIBER-RRMM1

LABORATORY
ABNORMALITY		 ZENBEXUS + Dd
(N=204)		 DVd
(N=204)
All grades (%) Grade 3–4 (%) All grades (%) Grade 3–4 (%)
Hematology        
Neutrophil count decreased  97 77 48 11
White blood cell count decreased 95 69 64 18
Lymphocyte count decreased 91 62 81 51
Platelet count decreased 62 9 92 46
Hemoglobin decreased 58 6 63 6
Chemistry        
Blood calcium decreased 44 2 28 1
Blood alkaline phosphatase increased 33 0.5 26 0.5

7.8% of patients discontinued ZENBEXUS due to ARs1

  • The most frequent AR which resulted in permanent ZENBEXUS discontinuation was neutropenia (1%)1
  • Fatal ARs occurred in 10 patients (4.9%) who received ZENBEXUS1
  • Sepsis (1.5%) was the only fatal drug reaction that occurred in more than 1 patient1
  • The following fatal ARs occurred in 1 patient each: listeria encephalitis, influenza, lung adenocarcinoma, cardiac arrest, large intestine perforation, metabolic acidosis, and respiratory failure1
  • Serious ARs occurred in 58.3% of patients who received ZENBEXUS1
  • Serious ARs in ≥2% of patients included pneumonia (26%), upper respiratory tract infection (6.4%), second primary malignancy (5.9%), neutropenia (4.9%), febrile neutropenia (3.9%), COVID-19 (4.4%), and sepsis (2.9%)1
  • Neutropenia was reported in all grades (90.2%), Grade 3 (30.9%), and Grade 4 (53.4%) of patients who received ZDd1
  • Febrile neutropenia occurred in 5.4% of patients who received ZDd1
  • Second primary malignancies occurred in 6.9% of patients with ZDd and 4.9% with DVd1

Adverse reactions were graded according to NCI CTCAE Version 5.0.
*Upper respiratory tract infection includes nasopharyngitis, pharyngitis, respiratory tract infection, sinusitis, and other related terms.1
†Includes fatal adverse reaction: ZDd (n=1).1
‡Pneumonia includes atypical pneumonia, bacterial pneumonia, lower respiratory tract infection, lung consolidation, viral pneumonia, and other related terms.1
§Includes other related terms.1
∥Motor dysfunction includes ataxia, balance disorder, gait disturbance, muscle contracture, muscle spasms, muscular weakness, myopathy, paralysis, peripheral motor neuropathy, and other related terms.1
Sensory neuropathy includes anosmia, hypoesthesia, mononeuropathy, neuralgia, paresthesia, peripheral neuropathy, peripheral sensory neuropathy, polyneuropathy, radiculopathy, and other related terms.1
#Sleep disorder includes insomnia, restless legs syndrome, sleep disorder, and other related terms.1
**Hypogammaglobulinemia includes hypogammaglobulinemia, hypoglobulinemia, and other related terms.1
††Hemorrhage includes epistaxis, gastrointestinal hemorrhage, hematuria, injection site hemorrhage, rectal hemorrhage, subarachnoid hemorrhage, subdural hematoma, and other related terms.1
‡‡The denominator used to calculate the rate varied from 201 to 204 for both ZDd and DVd arms based on the number of patients with a baseline value and at least one post-treatment value.1

APP=advanced practice provider; AR=adverse reaction; COVID-19=coronavirus disease 2019; Dd=daratumumab and hyaluronidase-fihj and dexamethasone; DVd=daratumumab and hyaluronidase-fihj, bortezomib, and dexamethasone; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; ZDd=ZENBEXUS, daratumumab and hyaluronidase-fihj, and dexamethasone.

Neutropenia/Infections

Timing of neutropenia and infections with ZENBEXUS

Graph of Neutropenia grade 3-4 events by cycle (ZDd). The median duration of Grade 3-4 neutropenia was 8 days and median time to onset was 21 days.

*Treatment-emergent Grade 3-4 neutropenia events.4
†Neutropenia includes both neutropenia and febrile neutropenia.

1% of patients discontinued due to neutropenia1

  • 80% (n=164) of patients received GCSF for a median of 4 treatments, primarily to manage neutropenia4,5†
  • 51.5% had a dose interruption due to neutropenia1
  • 14% (n=28) had a dose reduction due to neutropenia5
  • The rate of febrile neutropenia was 5.4% with no cases resulting in death1,4
  • Monitor complete blood count throughout treatment with ZENBEXUS. Interrupt, reduce dosage, or discontinue ZENBEXUS, as necessary. Initiate GCSF as appropriate per guidelines1
Graph of grade 3-4 infection events by cycle (ZDd). Infection rates were stable and remained below 10% across cycles.

1.5% of patients discontinued due to infections1

  • Grade 3 infections were reported in 35.8% of patients. Grade 4 infections were reported in 3.4%1
  • Most common Grade 3-4 infection was pneumonia (25%) with no cases resulting in death from pneumonia1,4
  • Serious infections occurred in 40% of patients1
  • 2% of cases of infections resulted in death in the ZDd arm1
  • Monitor patients for signs and symptoms of infection prior to and during treatment with ZENBEXUS and treat appropriately. Withhold or reduce the dose based on severity. Consider prophylactic anti-infective medications according to current practice guidelines1

How to START*

Learn about oral administration that fits into your existing workflow1,6†

When to ADJUST

Learn about dose adjustments available to manage ARs and keep patients on therapy if clinically appropriate1

Resources for APPs
and Nurses

Resources to help support your patients on treatment with ZENBEXUS + Dd

*Preinitiation pregnancy testing may be required for some patients.1
†Combination of oral therapies given with subcutaneous daratumumab and hyaluronidase-fihj.1

APP=advanced practice provider; AR=adverse reaction; Dd=daratumumab and hyaluronidase-fihj and dexamethasone; DVd=daratumumab and hyaluronidase-fihj, bortezomib, and dexamethasone; GCSF=granulocyte colony-stimulating factor; ZDd=ZENBEXUS, daratumumab and hyaluronidase-fihj, and dexamethasone.

References: 1. ZENBEXUS [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2026. 2. Dimopoulos MA, Oriol A, Nahi H, et al. N Engl J Med. 2016;375(14):1319-1331. doi:10.1056/NEJMoa1607751 3. Dimopoulos MA, Terpos E, Boccadoro M, et al. Lancet Oncol. 2021;22(6)801-812. doi:10.1016/S1470-2045(21)00128-5 4. Data on file. BMS-REF-00030-2070. Princeton, NJ: Bristol-Myers Squibb Company; 2026. 5. Data on file. BMS-REF-00043-2070. Princeton, NJ: Bristol-Myers Squibb Company; 2026. 6. Data on file. BMS-REF-NONE-0010. Princeton, NJ: Bristol-Myers Squibb Company; 2026.

References

IMPORTANT SAFETY
INFORMATION

WARNING: EMBRYO-FETAL TOXICITY AND SERIOUS VENOUS AND ARTERIAL THROMBOEMBOLISM

EMBRYO-FETAL TOXICITY

ZENBEXUS is contraindicated in pregnancy. ZENBEXUS is embryo-fetal toxic in animals and can cause birth defects or embryo-fetal death in humans. In females of reproductive potential, obtain 2 negative pregnancy tests before starting ZENBEXUS treatment.

Females of reproductive potential must use 2 effective forms of contraception or continuously abstain from heterosexual sex during and for 4 weeks after last dose of ZENBEXUS treatment.

Because of the risk of embryo-fetal toxicity, ZENBEXUS is only available through a restricted distribution program called ZENBEXUS REMS.

SERIOUS VENOUS AND ARTERIAL THROMBOEMBOLISM

Increased risk of deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, and stroke in patients with multiple myeloma receiving ZENBEXUS with daratumumab and hyaluronidase-fihj and dexamethasone. Anti-thrombotic prophylaxis is recommended.

CONTRAINDICATIONS

Based on the mechanism of action and findings in animal studies, ZENBEXUS can cause birth defects or embryo-fetal death in humans. ZENBEXUS is contraindicated in females who are pregnant. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus.

WARNINGS AND PRECAUTIONS

Embryo-Fetal Toxicity

Females of Reproductive Potential: Must avoid pregnancy while taking ZENBEXUS and for at least 4 weeks after completing therapy. Advise females of reproductive potential of the potential risk to a fetus and to use 2 methods of effective contraception for at least 4 weeks before beginning ZENBEXUS therapy, during therapy, during dose interruptions and for at least 4 weeks after the last dose of ZENBEXUS therapy. Refer patients who can become pregnant to a qualified provider of contraceptive methods, if needed.

Two negative pregnancy tests with a sensitivity of at least 25 mIU/mL must be obtained prior to initiating therapy. Pregnancy testing should be performed weekly during the first 4 weeks of treatment. Thereafter, testing should occur every 4 weeks in patients with regular menstrual cycles, or every 2 weeks in patients with irregular menstrual cycles.

Females of reproductive potential taking ZENBEXUS must not donate eggs during treatment and for 4 weeks after completion.

Males: ZENBEXUS may pass into human semen. Advise patients who can impregnate partners to use effective contraception during treatment and for 4 weeks following the discontinuation of ZENBEXUS therapy. Male patients taking ZENBEXUS must not donate sperm during treatment and for 4 weeks after completion.

Blood Donation: Patients must not donate blood during treatment with ZENBEXUS and for 4 weeks following discontinuation of ZENBEXUS therapy.

ZENBEXUS REMS

ZENBEXUS is available only through a restricted program called ZENBEXUS REMS, because of the risk of embryo-fetal toxicity. Prescribers must be certified with, and patients must be enrolled in the ZENBEXUS REMS Program and comply with ongoing monitoring and contraception requirements. Further information about ZENBEXUS REMS, including information for pharmacies, wholesalers, and distributors, is available at www.ZENBEXUSREMS.com or by telephone at 1-888-423-5436.

Serious Venous and Arterial Thromboembolism

ZENBEXUS can cause serious and life-threatening venous thromboembolic events (DVT and PE) and arterial thromboembolic events (myocardial infarction and stroke). In the EXCALIBER-RRMM study (N=204), venous thromboembolic events occurred in 6.4% of patients treated with ZENBEXUS combined with daratumumab and hyaluronidase-fihj and dexamethasone (IberDd) despite mandatory thromboembolism prophylaxis. The incidence of DVT was 3.4% and the incidence of PE was 1.5%.

Arterial thromboembolic events occurred in 3.4% of patients. The incidence of myocardial infarction was 2.0%, and the incidence of stroke (CVA) was 1.5%.

Monitor patients for signs and symptoms of thromboembolic events during treatment with ZENBEXUS. Patients with known risk factors, including prior thrombosis, may be at greater risk, and actions should be taken to try to minimize all modifiable factors (e.g., hyperlipidemia, hypertension, smoking). Thromboprophylaxis is recommended, and the choice of regimen should be based on assessment of the patient's underlying risk factors. In patients who develop a thromboembolism, interrupt ZENBEXUS and initiate anticoagulant therapy according to guidelines.

Neutropenia

ZENBEXUS can cause severe neutropenia. In the EXCALIBER-RRMM study, all-grade neutropenia was reported in 90.2%, Grade 3 in 30.9%, and Grade 4 in 53.4% of patients in the IberDd arm. Febrile neutropenia occurred in 5.4% of patients.

Monitor complete blood count throughout treatment with ZENBEXUS. Interrupt, reduce dosage, or discontinue ZENBEXUS, as necessary. Initiate granulocyte colony-stimulating factor (GCSF) as appropriate per guidelines.

Infections

ZENBEXUS can cause serious infections, including life-threatening or fatal infections. Patients with active or uncontrolled infection should not start ZENBEXUS treatment until the infection is controlled. In the EXCALIBER-RRMM study, infections, including opportunistic infections, were reported in 78.9%, Grade 3 in 35.8%, Grade 4 in 3.4%, and fatal infections in 2% of patients receiving IberDd. Serious infections occurred in 40% of patients. Discontinuations due to infections occurred in 1.5% of patients.

Monitor patients for signs and symptoms of infection prior to and during treatment with ZENBEXUS and treat appropriately. Withhold or reduce the dose based on severity.

Consider prophylactic anti-infective medications according to current practice guidelines.

Second Primary Malignancies

In the EXCALIBER-RRMM study, at a median follow-up time of 16 months, second primary malignancies (SPM) occurred in 6.9% of patients in the IberDd arm and 4.9% of patients in the daratumumab and hyaluronidase-fihj, bortezomib, and dexamethasone (DVd) arm.

Monitor patients for the development of SPM.

ADVERSE REACTIONS

Serious adverse reactions occurred in 58.3% of patients receiving ZENBEXUS. Serious adverse reactions in ≥2% of patients included pneumonia (26%), upper respiratory tract infection (6.4%), SPM (5.9%), neutropenia (4.9%), febrile neutropenia (3.9%), COVID-19 (4.4%), and sepsis (2.9%). Fatal adverse reactions occurred in 10 patients (4.9%) who received ZENBEXUS. Sepsis (1.5%) was the only fatal drug reaction that occurred in more than 1 patient. The following fatal adverse reactions occurred in 1 patient each: listeria encephalitis, influenza, lung adenocarcinoma, cardiac arrest, large intestine perforation, metabolic acidosis, and respiratory failure.

The most common adverse reactions (≥20%) in the IberDd arm and DVd arm, respectively, were upper respiratory tract infection (54% and 52%), fatigue (36% and 33%), musculoskeletal pain (35% and 33%), pneumonia (34% and 17%), diarrhea (33% and 36%), motor dysfunction (26% and 17%), rash (26% and 15%), sleep disorder (25% and 28%), hypogammaglobulinemia (24% and 12%), COVID-19 (23% and 16%), and constipation (20% and 22%).

The most common Grade 3 to 4 laboratory abnormalities (≥30%) in the IberDd arm and DVd arm, respectively, were neutropenia (77% and 11%), leukopenia (69% and 18%), and lymphopenia (62% and 51%).

DRUG INTERACTIONS

Effects of Other Drugs on ZENBEXUS

Strong or Moderate CYP3A Inhibitors: Coadministration of ZENBEXUS with strong or moderate CYP3A inhibitors should be avoided. If a strong or moderate CYP3A inhibitor must be used in combination with ZENBEXUS, reduce the ZENBEXUS dose. Concomitant use with strong or moderate CYP3A inhibitors may increase the risk of adverse reactions.

Strong or Moderate CYP3A Inducers: Coadministration of ZENBEXUS with strong or moderate CYP3A inducers should be avoided. Concomitant use with a strong or moderate CYP3A inducer may decrease the efficacy of ZENBEXUS.

SPECIFIC POPULATIONS

Pregnancy (See Boxed WARNINGS)

There is a pregnancy exposure registry that monitors outcomes in patients exposed to ZENBEXUS during pregnancy. See the ZENBEXUS REMS WARNINGS AND PRECAUTIONS section.

Lactation

Advise women not to breastfeed during treatment with ZENBEXUS. Refer to the Prescribing Information for daratumumab and hyaluronidase-fihj or dexamethasone for additional information.

Females and Males of Reproductive Potential

ZENBEXUS can cause fetal harm when administered during pregnancy.

Pregnancy Testing, Females of Reproductive Potential, and Males: See the Embryo-Fetal Toxicity WARNINGS AND PRECAUTIONS section.

Geriatric Use

In patients treated with IberDd, the incidence of serious adverse reactions was 53%, 56%, and 74% in adult patients younger than 65 years of age, 65 years of age to younger than 75 years of age, and 75 years of age and older, respectively.

Renal Impairment

Reduce the ZENBEXUS dose in patients with estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 not on dialysis. If dose modification is needed due to adverse events, reduce the ZENBEXUS dose to 1 mg every other day on Days 1 to 21 of a 28-day cycle.

Please see full Prescribing Information for ZENBEXUS including Boxed WARNINGS.

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ZENBEXUS and its associated logo are trademarks of Celgene Corporation, a Bristol Myers Squibb company.
All other trademarks are the property of their respective owners.

© 2026 Bristol-Myers Squibb Company.

2070-US-2600011  08/26