What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, such as Daratumumab (a monoclonal antibody targeting CD38), bortezomib, lenalidomide, and dexamethasone, have several known side effects. Daratumumab can cause neutropenia, lymphocytopenia, and higher rates of infections, including pneumonia and viral reactivations (e.g., herpes zoster, CMV). Bortezomib is associated with peripheral neuropathy, gastrointestinal issues, and thrombocytopenia. Lenalidomide can lead to neutropenia, thrombocytopenia, and an increased risk of venous thromboembolism. Dexamethasone, a corticosteroid, may cause hyperglycemia, insomnia, and increased risk of infections. When used in combination, these treatments can have compounded side effects, necessitating careful monitoring and management.

What prior FDA approvals exist?

Daratumumab, an anti-CD38 monoclonal antibody, has been approved by the FDA for the treatment of multiple myeloma, both as a monotherapy and in combination with other agents such as bortezomib, lenalidomide, and dexamethasone. Other similar treatments include isatuximab, another anti-CD38 monoclonal antibody, which has been approved for use in combination with pomalidomide and dexamethasone. These approvals are based on their demonstrated efficacy in improving progression-free survival and overall response rates in patients with relapsed or refractory multiple myeloma.

What other types of research exist?

Promising novel alternatives to Daratumumab for Multiple Myeloma patients include: 1) Isatuximab, another anti-CD38 monoclonal antibody, which has shown efficacy in combination with pomalidomide and dexamethasone. 2) Belantamab mafodotin, an antibody-drug conjugate targeting BCMA (B-cell maturation antigen), which has demonstrated activity in heavily pretreated patients. 3) Teclistamab, a bispecific antibody targeting BCMA and CD3, which has shown promising results in early-phase trials. 4) CAR T-cell therapies targeting BCMA, such as idecabtagene vicleucel and ciltacabtagene autoleucel, which have shown high response rates in relapsed/refractory multiple myeloma.

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Proteasome Inhibitor

Daratumumab + VRd for Multiple Myeloma

Phase 3

Waitlist Available

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

Diagnosis of multiple myeloma as documented per International Myeloma Working Group (IMWG) criteria

Must not have

Prior therapy for multiple myeloma other than a short course of corticosteroids (not to exceed 40 mg of dexamethasone, or equivalent per day, total of 160 mg dexamethasone or equivalent)

Peripheral neuropathy or neuropathic pain Grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from randomization until the participant's death from any cause (up to approximately 6 years, or 9 years if the adaptive approach is decided at the interim)

Awards & highlights

Pivotal Trial

No Placebo-Only Group

Summary

This trial is testing if adding daratumumab to an existing three-drug treatment will improve outcomes for newly diagnosed multiple myeloma patients who are not planning a stem cell transplant. The combination of drugs works together to kill cancer cells in different ways. Daratumumab has shown efficacy in improving overall survival and progression-free survival in multiple myeloma patients when added to other treatment regimens.

Who is the study for?

This trial is for adults with untreated multiple myeloma who don't plan to have a stem cell transplant right away. They must have measurable disease, be able to perform daily activities (ECOG score 0-2), and women of childbearing age need two negative pregnancy tests before dosing. People can't join if they've had other cancer treatments or certain health conditions like severe neuropathy.

What is being tested?

The study is testing whether adding Daratumumab to the combination of Bortezomib, Lenalidomide, and Dexamethasone (D-VRd) improves outcomes compared to just VRd in treating multiple myeloma. The main goal is seeing if this mix reduces the number of remaining cancer cells better than the standard combo.

What are the potential side effects?

Possible side effects include immune system reactions, nerve damage symptoms like numbness or pain, blood clots, low blood counts leading to increased infection risk or bleeding problems, fatigue, digestive issues such as nausea or constipation, and potential harm to an unborn baby.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can take care of myself and am up and about more than half of my waking hours.

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I have been diagnosed with multiple myeloma according to IMWG standards.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have only used a short course of corticosteroids for my multiple myeloma.

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I have moderate to severe nerve pain or damage.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from randomization until the participant's death from any cause (up to approximately 6 years, or 9 years if the adaptive approach is decided at the interim)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from randomization until the participant's death from any cause (up to approximately 6 years, or 9 years if the adaptive approach is decided at the interim)

This trial's timeline: 3 weeks for screening, Varies for treatment, and from randomization until the participant's death from any cause (up to approximately 6 years, or 9 years if the adaptive approach is decided at the interim) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Percentage of Participants with Negative Minimal Residual Disease (MRD) Status

Secondary study objectives

Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L)

Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30)

Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Multiple Myeloma 20-item (EORTC QLQ-MY20)

+14 more

Side effects data

From 2022 Phase 3 trial • 402 Patients • NCT03110562

50%

Thrombocytopenia

45%

Anaemia

39%

Nausea

29%

Diarrhoea

29%

Decreased appetite

27%

Weight decreased

24%

Neuropathy peripheral

24%

Vomiting

23%

Fatigue

21%

Neutropenia

21%

Cataract

15%

Asthenia

12%

Upper respiratory tract infection

11%

Constipation

11%

Pyrexia

Oedema peripheral

Pneumonia

Insomnia

Dehydration

Back pain

Leukopenia

Bronchitis

Dizziness

Cough

Lymphopenia

Acute kidney injury

Muscular weakness

Abdominal pain

Lower respiratory tract infection

Sepsis

Hyperglycaemia

Pain in extremity

Urinary tract infection

Nasopharyngitis

Hyponatraemia

Toothache

Disturbance in attention

Cardiac failure

Hypertension

Septic shock

Pulmonary contusion

Peripheral swelling

Infection

Blood creatinine increased

Paraesthesia

Respiratory syncytial virus infection

Dyspepsia

Syncope

Cardiac failure acute

Clostridium difficile infection

Compression fracture

Multiple fractures

Haemoglobin decreased

Myocardial infarction

Cerebral haemorrhage

C-reactive protein increased

Ischaemic stroke

Sudden death

Oropharyngeal pain

Cognitive disorder

Confusional state

Influenza

Osteonecrosis of jaw

Taste disorder

Hyperkalaemia

Blood uric acid increased

Depression

Cerebrovascular accident

Embolism

Bronchitis viral

100%

80%

60%

40%

20%

Study treatment Arm

SVdX Arm: Selinexor + Bortezomib + Dexamethasone

SdX Arm: Selinexor + Dexamethasone

SVd Arm: Selinexor + Bortezomib + Dexamethasone

Vd Arm: Bortezomib + Dexamethasone

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Daratumumab + VRd (D-VRd) and DRdExperimental Treatment4 Interventions

Participants will receive daratumumab 1800 mg as SC injection once every week for Cycles 1 to 2, then every 3 weeks for Cycles 3 through 8 and every 4 weeks for Cycle 9 and beyond; bortezomib 1.3 mg/m\^2 as SC injection twice weekly on Days 1, 4, 8, 11 for Cycles 1 through 8 (each cycle is of 21 days); lenalidomide 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9; dexamethasone 20 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, 12 for Cycles 1 through 8 and 40 mg on Days 1,8, 15 and 22 during Cycle 9 and beyond followed by daratumumab-lenalidomide-dexamethasone (DRd) until disease progression or unacceptable toxicity.

Group II: Bortezomib + Lenalidomide + Dexamethasone (VRd) and RdActive Control3 Interventions

Participants will receive bortezomib 1.3 milligram per square meter (mg/m\^2) as subcutaneous (SC) injection twice weekly on Days 1, 4, 8, 11 for Cycles 1 through 8 (each cycle is of 21 days); lenalidomide 25 mg orally on Day 1 to Day 14 for Cycles 1 through 8 and on Days 1 to 21 for Cycle 9 (cycle of 28 days); dexamethasone 20 mg orally or intravenously on Days 1, 2, 4, 5, 8, 9, 11, 12 for Cycles 1 through 8 and 40 mg on Days 1,8, 15 and 22 during Cycle 9 and beyond (each cycle is of 28 days) followed by lenalidomide-dexamethasone (Rd) until disease progression or unacceptable toxicity.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Daratumumab

2014

Completed Phase 3

~2380

Bortezomib

2005

Completed Phase 3

~1410

Lenalidomide

2005

Completed Phase 3

~2240

Dexamethasone

2007

Completed Phase 4

~2650

0 / 4Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Daratumumab is a monoclonal antibody that targets CD38 on myeloma cells, inducing cell death through immune-mediated mechanisms. Bortezomib is a proteasome inhibitor that disrupts protein degradation, leading to apoptosis of myeloma cells. Lenalidomide is an immunomodulatory drug that enhances immune response against myeloma cells and inhibits their growth. Dexamethasone is a corticosteroid that reduces inflammation and directly induces apoptosis in myeloma cells. These mechanisms are crucial as they target different pathways essential for myeloma cell survival, providing a comprehensive approach to treatment and improving patient outcomes.