What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, especially those involving monoclonal antibodies like Isatuximab, often result in side effects such as neutropenia, infections (including upper respiratory tract infections and pneumonia), and infusion-related reactions. When combined with drugs like bortezomib, lenalidomide, and dexamethasone, additional side effects can include gastrointestinal distress, peripheral neuropathy, fatigue, and cytopenias (anemia, thrombocytopenia). These treatments aim to prolong progression-free survival and improve overall response rates but require careful management of these adverse effects.

What prior FDA approvals exist?

Isatuximab, a monoclonal antibody targeting CD38, has been approved for the treatment of relapsed/refractory multiple myeloma. Similar drugs include Daratumumab, another anti-CD38 monoclonal antibody, which has been approved for use in combination with various agents such as bortezomib, melphalan, prednisone, lenalidomide, and dexamethasone. These combinations have shown efficacy in both newly diagnosed and relapsed/refractory multiple myeloma patients. Other related treatments include Elotuzumab, targeting SLAMF7, and Belantamab mafodotin, targeting BCMA, although the latter has been withdrawn from the U.S. market.

What other types of research exist?

Promising novel alternatives to Isatuximab for Multiple Myeloma patients include: 1) Daratumumab (another CD38-targeting monoclonal antibody), 2) Elotuzumab (targets SLAMF7), 3) Belantamab mafodotin (an antibody-drug conjugate targeting BCMA), 4) Teclistamab (a bispecific antibody targeting BCMA and CD3), and 5) CAR T-cell therapies such as Idecabtagene vicleucel and Ciltacabtagene autoleucel, both targeting BCMA.

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Proteasome Inhibitor

Isatuximab + VRd for Multiple Myeloma (IMROZ Trial)

Q: What is the mechanism of action of this treatment?

The most common treatments for Multiple Myeloma include monoclonal antibodies like Isatuximab, which targets CD38 on myeloma cells, leading to cell death through immune-mediated mechanisms. Other treatments include proteasome inhibitors (e.g., bortezomib) that disrupt protein degradation, immunomodulatory drugs (e.g., lenalidomide) that enhance immune response and inhibit myeloma cell growth, and corticosteroids (e.g., dexamethasone) that reduce inflammation and kill myeloma cells. These mechanisms are crucial for Multiple Myeloma patients as they target the cancer cells directly, improve immune system function, and manage symptoms, thereby improving survival rates and quality of life.

Phase 3

Waitlist Available

Research Sponsored by Sanofi

Eligibility Criteria Checklist

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

Must have

Multiple myeloma (IMWG criteria)

Newly diagnosed multiple myeloma not eligible for transplant due to age (≥ 65 years) or patients < 65 years with comorbidities impacting possibility of transplant

Must not have

Organ function values not met

Male participants who disagree to follow the study contraceptive counseling

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 days after end of treatment (eot) visit

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new drug called isatuximab added to a standard treatment mix. It targets patients with newly diagnosed multiple myeloma who can't have a transplant. Isatuximab helps the immune system destroy cancer cells, while the other drugs kill cancer cells and reduce inflammation.

Who is the study for?

This trial is for adults with newly diagnosed multiple myeloma who can't have a transplant because they're over 65 or under 65 with other health issues. They must have measurable disease signs and agree to use contraception if necessary. It's not for those under 18, previously treated for myeloma, or with certain health conditions that could interfere.

What is being tested?

The study tests whether adding Isatuximab (SAR650984) to the combo of Bortezomib, Lenalidomide, and Dexamethasone improves survival without cancer progression in new multiple myeloma patients ineligible for transplant compared to just the three-drug combo.

What are the potential side effects?

Possible side effects include reactions at the infusion site, increased risk of infections due to low blood cell counts, nerve damage causing pain or numbness (neuropathy), blood clots, diarrhea, fatigue, and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with multiple myeloma.

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I am over 65 or have health issues that prevent a bone marrow transplant for my newly diagnosed multiple myeloma.

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I am over 65 or have health issues that prevent a bone marrow transplant for my newly diagnosed multiple myeloma.

Exclusion Criteria

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

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My organ functions are not within the required range.

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I am a male and agree to follow contraceptive advice during the study.

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I am under 18 years old.

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I have received treatment for multiple myeloma before.

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My daily activity is significantly limited due to my health.

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I am not pregnant, breastfeeding, and if capable of bearing children, I agree to use contraception.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 days after end of treatment (eot) visit

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 days after end of treatment (eot) visit

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 30 days after end of treatment (eot) visit for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Progression free survival (PFS)

Secondary study objectives

Adverse Events

Assessment of PK parameter: Ctrough

Complete response rate (CR)

+15 more

Side effects data

From 2022 Phase 3 trial • 402 Patients • NCT03110562

43%

Weight decreased

29%

Decreased appetite

29%

Cough

29%

Thrombocytopenia

29%

Nausea

21%

Fatigue

21%

Anaemia

21%

Constipation

21%

Diarrhoea

14%

Neuropathy peripheral

14%

Oedema peripheral

14%

Pneumonia

14%

Paraesthesia

14%

Cataract

14%

Vomiting

14%

Headache

Urinary tract infection

Bronchiectasis

Asthma

Disturbance in attention

Respiratory syncytial virus infection

Neutropenia

Peripheral swelling

Mental status changes

Lower respiratory tract infection

Hyperthyroidism

Back pain

Pain in extremity

Basal cell carcinoma

Hyponatraemia

Skin lesion

Oropharyngeal pain

Pyrexia

Cardiac failure

Hepatitis

Pharyngitis

Hypophagia

Pollakiuria

Non-cardiac chest pain

C-reactive protein increased

Taste disorder

Haemorrhagic transformation stroke

Abdominal pain

Insomnia

Dyspepsia

Haemoglobin decreased

Infection

Hyperglycaemia

Toothache

Ecchymosis

Upper respiratory tract infection

Nasopharyngitis

Fungal skin infection

Viral infection

Hypertension

Muscular weakness

100%

80%

60%

40%

20%

Study treatment Arm

SdX Arm: Selinexor + Dexamethasone

SVdX Arm: Selinexor + Bortezomib + Dexamethasone

SVd Arm: Selinexor + Bortezomib + Dexamethasone

Vd Arm: Bortezomib + Dexamethasone

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

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

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Isatuximab/Lenalidomide/Dexamethasone = IRd crossover armExperimental Treatment3 Interventions

4-weeks cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone

Group II: Isatuximab/Bortezomib/Lenalidomide/Dexamethasone = IVRd armExperimental Treatment4 Interventions

1. Induction treatment with 4x6-week cycles with intravenous (IV) isatuximab + subcutaneous (SC) bortezomib + oral lenalidomide + IV or oral dexamethasone 2. Continuous treatment with 4-week cycles with IV isatuximab + oral lenalidomide + IV or oral dexamethasone

Group III: Bortezomib/Lenalidomide/Dexamethasone = VRd armActive Control3 Interventions

1. Induction treatment with 4x6-week cycles with SC bortezomib + oral lenalidomide + IV or oral dexamethasone 2. Continuous treatment with 4-week cycles with oral lenalidomide + IV or oral dexamethasone

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Dexamethasone

2007

Completed Phase 4

~2650

Bortezomib

2005

Completed Phase 3

~1410

Isatuximab SAR650984

2015

Completed Phase 2

~580

Lenalidomide

2005

Completed Phase 3

~2240

0 / 9Eligibility 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

The most common treatments for Multiple Myeloma include monoclonal antibodies like Isatuximab, which targets CD38 on myeloma cells, leading to cell death through immune-mediated mechanisms. Other treatments include proteasome inhibitors (e.g., bortezomib) that disrupt protein degradation, immunomodulatory drugs (e.g., lenalidomide) that enhance immune response and inhibit myeloma cell growth, and corticosteroids (e.g., dexamethasone) that reduce inflammation and kill myeloma cells. These mechanisms are crucial for Multiple Myeloma patients as they target the cancer cells directly, improve immune system function, and manage symptoms, thereby improving survival rates and quality of life.