Isatuximab-VRd in Transplant-Ineligible Newly Diagnosed Multiple Myeloma Patients

A Single-Arm, Multicenter, Prospective, Observational Clinical Study on the Efficacy and Safety of Isatuximab Combined With Bortezomib, Lenalidomide, and Dexamethasone (Isa-VRd) Regimen in Transplant-Ineligible Newly Diagnosed Multiple Myeloma (TI-NDMM) Patients

Primary Objective of the trial is to evaluate the efficacy and safety of Isa-VRd-based regimen in transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM) patients receiving treatment in real-world clinical practice in China.

And Secondary Objectives is， To assess the MRD negativity rate in Chinese TI-NDMM patients treated with Isa-VRd To assess the safety and tolerability of Isa-VRd in Chinese TI-NDMM patients

Participants will:

Receive Isatuximab 10 mg/kg iv

• Cycle 1: Every weeks on Days 1, 8, 15, and 22
• Cycles 2-8: Every 2 weeks on Days 1 and 15 Receive Bortezomib subcutaneous injection 1.3 mg/m²
• Cycles 1-8: Days 1, 8, and 15 of each cycle Receive Lenalidomide oral 25 mg/day
• Cycles 1-8: Days 1-21 at 25 mg/day (10 mg/day for patients with creatinine clearance [CrCl] ≥30 and <60 mL/min) Receive Dexamethasone oral 20 mg
• Cycles 1-8: Days 1, 8, 15, and 22 of each cycle Following Cycle 8, the investigator may assess and adjust the treatment regimen During the induction phase, efficacy assessment is recommended at each treatment cycle. Patients who achieve ≥CR at the end of induction are recommended to undergo the first MRD monitoring assessment.

During the maintenance phase, efficacy assessment is recommended at least every 3 cycles. Patients are recommended to undergo MRD status monitoring (≥CR) every 6 months (i.e., at months 14, 20, and 26) for MRD assessment.

During the follow-up period, MRD status monitoring (≥CR) is recommended every 12 months to observe the depth of response.

This is a single-arm, multicenter, prospective observational cohort study with a planned total enrollment of 333 transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM) patients aged ≥18 years old in China. All enrolled participants will receive the Isa-VRd induction regimen for 8 cycles (4 weeks per cycle, total 32 weeks). After induction therapy, investigators will determine whether patients continue maintenance treatment based on individual response status, followed by a 2-year long-term follow-up period from the initiation of Isa-VRd treatment, with the maximum observation window of each subject capped at 24 months.

For efficacy evaluation, minimal residual disease (MRD) testing with a cutoff of NGF=10-⁵ will be performed at multiple prespecified time points: at month 8 post-induction, and every 6 months throughout the maintenance and follow-up phase (at months 14, 20 and 26). The primary endpoint of this study is ≥CR rate after induction therapy. Secondary efficacy endpoints include stringent complete response (sCR), very good partial response (VGPR), overall response rate (ORR), duration of response (DOR), time to response (TTR), time to next treatment (TNT), progression-free survival (PFS), overall survival (OS), as well as all safety and tolerability outcomes.

Throughout the entire treatment and follow-up period, all treatment-emergent adverse events (TEAEs), grade ≥3 adverse events, serious adverse events (SAEs), and adverse events of special interest (AESIs, including infusion reactions and second primary malignancies) will be continuously collected and recorded to evaluate the real-world safety profile of the Isa-VRd regimen in Chinese TI-NDMM patients. The overall planned study duration spans approximately 24 months from the first subject's enrollment to the completion of the last patient's 24-month follow-up assessment.

Inclusion Criteria:

• Age ≥18 years

• Newly diagnosed transplant-ineligible multiple myeloma patients as assessed by investigator, specifically referring to CSCO guidelines

• Must meet corresponding laboratory test results (refer to restrictions in package inserts of combination drugs):

  • Absolute neutrophil count (ANC) ≥1.0×10⁹/L
  • Platelet count ≥50×10⁹/L
  • Calculated creatinine clearance ≥30 mL/min (using Cockcroft-Gault formula)
  • Total bilirubin ≤3× upper limit of normal (ULN)

• TI-NDMM patients intended for Isa-VRd regimen treatment as determined by investigator judgment, independent of study objectives Signed informed consent form (by patient or their legal representative)

Exclusion Criteria:

• Patients currently participating in other interventional clinical studies

• Patients with known severe hypersensitivity reactions to Isatuximab or any other excipients

• Severe bacteremia at the time of administration

• Currently uncontrolled cardiovascular disease, including:

  • Uncontrolled hypertension
  • Uncontrolled arrhythmia
  • Uncontrollable congestive heart failure
  • Unstable angina

• Patients with peripheral neuropathy ≥Grade 2

• Active infectious disease, known human immunodeficiency virus (HIV) positivity, active hepatitis B or hepatitis C

• Patients who are currently pregnant

• Patients who, at the physician's discretion, are unable to tolerate any drug in the combination regimen