Safety and Efficacy of Elranatamab Plus Isatuximab, Bortezomib, and Lenalidomide in Ultra-High-Risk Multiple Myeloma

A Clinical Study Evaluating the Safety and Efficacy of Elranatamab in Combination With Isatuximab, Bortezomib, and Lenalidomide in Patients With Ultra-High-Risk Multiple Myeloma.

This is a prospective, single-arm, single-center interventional study designed to evaluate the safety and efficacy of Elra-Isa-VR in patients with newly diagnosed ultra-high-risk multiple myeloma.

Inclusion Criteria:

1. The subject voluntarily signs the informed consent form (ICF).
2. Aged 18-70 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

Newly diagnosed multiple myeloma according to the International Myeloma Working Group (IMWG) diagnostic criteria, with measurable disease meeting at least one of the following criteria:

1. Serum M-protein ≥1.0 g/dL
2. Urine M-protein ≥200 mg/24 hours
3. Serum involved free light chain ≥10 mg/dL with an abnormal serum free light-chain ratio 4.High-risk multiple myeloma according to the Consensus Genomic Staging (CGS) system published by the International Myeloma Society-International Myeloma Working Group (IMS-IMWG), or peripheral blood plasma cells ≥2%, or an extramedullary soft-tissue mass (EME). High-risk CGS is defined by at least one of the following criteria:

（1）del(17p) with a clonal fraction >20% and/or a TP53 mutation （2）An IGH translocation [t(4;14), t(14;16), or t(14;20)] combined with 1q+ or del(1p32) （3）del(1p32), defined as monoallelic deletion combined with 1q+ or biallelic deletion （5）β2-microglobulin ≥5.5 mg/L with a normal serum creatinine level

Exclusion Criteria:

1. Concurrent plasma cell leukemia, central nervous system involvement, or amyloidosis.
2. Peripheral neuropathy of Grade >1, or Grade 1 peripheral neuropathy with pain. Prior or ongoing systemic therapy or stem cell transplantation for symptomatic multiple myeloma, except for the emergency use of a short course of corticosteroids equivalent to dexamethasone 40 mg/day for 4 days, provided that the course is completed within 14 days before randomization.
3. Any contraindication to, or a history of life-threatening allergy, hypersensitivity, or intolerance to, any study drug or its excipients.
4. Pregnant or breastfeeding, or planning to become pregnant during participation in the study or within 6 months after the last dose of any study treatment.
5. Planning to father a child during participation in the study or within 100 days after the last dose of any component of the study treatment regimen.