Breakthrough Clinical Results

Regeneron Pharmaceuticals announced positive initial results from the Phase 1b LINKER-MM2 trial evaluating linvoseltamab in combination with carfilzomib or bortezomib for relapsed/refractory multiple myeloma (MM). The trial included patients who had progressed after at least two prior lines of therapy. In the carfilzomib cohort, a 90% objective response rate (ORR) was observed with a median follow-up of 15 months. The bortezomib cohort showed an 85% ORR with a median follow-up of 9 months. These results will be presented at the ASCO 2025 Annual Meeting. A Phase 3 trial is planned. Linvoseltamab is already approved in the EU for later-line treatment of R/R MM and is under FDA review in the US.

Incidence and Prevalence

Global Incidence and Prevalence of Multiple Myeloma

Multiple myeloma (MM) has an incidence of 4-6 per 100,000 inhabitants. The incidence increases markedly with age.

Multiple myeloma has an increasing global incidence and a poor prognosis.

The incidence of MM is on the rise in China due to the aging of the population.

Risk Factors and Comorbidities

Recent Studies

Recent Multiple Myeloma Studies: Interventions and Outcomes

IMiD-14 Signature Study

• Intervention: Immunomodulatory derivatives (IMiDs) - thalidomide, lenalidomide, pomalidomide

• Key Results:

• Created a 14-gene signature (IMiD-14) to identify patients likely to benefit from IMiD therapies

• In the training cohort, 3-year progression-free survival was 52% for IMiD-14 high score vs 85% for IMiD-14 low score (HR 2.51)

• Validated in multiple cohorts: TT3a, TT3b, TT6, and HOVON65/GMMG-HD4 trials

• The model had prognostic value in patients with multiple myeloma treated with IMiDs

Isatuximab Real-World Experience

• Intervention: Isatuximab-based therapy (anti-CD38 monoclonal antibody)

• Key Results:

• Three patients were previously exposed to daratumumab (another anti-CD38 mAb)

• Isatuximab provided clinical benefit to all three daratumumab-exposed patients

• Showed efficacy in patients with renal insufficiency

• Demonstrated isatuximab's clinical potential in real-world setting

Pyroptosis-Related Genes Study

• Intervention: Risk stratification model based on pyroptosis-related genes (PRGs)

• Key Results:

• Identified 33 PRGs from TCGA database, defining 4 molecular subtypes

• Patients in cluster 1 had poorer survival than those in cluster 2 (p=0.035)

• 9 PRGs were identified as prognostic markers with best predictive ability for 3-year survival (AUC=0.658)

• High-risk group had worse survival than low-risk group (p<0.001)

• Nomogram combining gender, age, ISS stage, and risk score had best prognostic performance (c-index of 0.721)

Myeloma Series Studies

• Three UK clinical trials with the same name were identified: Myeloma IX, Myeloma XI, and TEAMM
• These trials enrolled 6,399 newly diagnosed multiple myeloma patients
• The studies identified 44 patients with biclonal gammopathy multiple myeloma with IgG or IgA MGUS clones

Additional Multiple Myeloma Interventions

• Anti-BCMA CAR T-cell therapy
• Combined CAR T-cell therapy
• Antibody-drug conjugates
• Bispecific antibody therapy
• CELMoDs (Cereblon E3 ligase modulators)
• Proteasome inhibitors (bortezomib and ixazomib)
• Continuous low-dose cyclophosphamide combined with prednisone (CP)
• Combination regimens such as bortezomib with thalidomide (VT), lenalidomide (VR), doxorubicin (VD), or cyclophosphamide (VC)

Drug used in other indications

Trials of Linvoseltamab and Carfilzomib Beyond Multiple Myeloma

Based on the provided context, there is no information available about linvoseltamab being trialed for Multiple Myeloma or any other indications. The context does not mention linvoseltamab clinical trials or their intervention models.

For carfilzomib, the context only provides information about its use in Multiple Myeloma (MM) treatments, specifically:

• Carfilzomib has been approved for treating patients with Multiple Myeloma who have received at least two prior therapies, including bortezomib and immunomodulatory derivatives (IMiDs, thalidomide, lenalidomide or pomalidomide)

• Carfilzomib has shown efficacy in clinical trials for MM patients with high-risk cytogenetic abnormalities:

• Bortezomib and carfilzomib treatment appear to improve complete response, progression-free survival, and overall survival in t(4;14) and del(17/17p)

• Carfilzomib-based induction-intensification-consolidation regimens are effective strategies in patients with standard risk and high-risk myeloma

• Despite promising progression-free survival, patients with ultra-high-risk disease (those with 2 or more HRCA) still have an increased risk of progression and death

• Carfilzomib has been studied in combination with various agents for MM:

• In combination with panobinostat for relapsed/refractory multiple myeloma

• With lenalidomide and dexamethasone (KRd) induction

• With cyclophosphamide and dexamethasone (KCd)

• Carfilzomib plus lenalidomide maintenance prolonged progression-free survival compared with lenalidomide maintenance alone

The context suggests limited efficacy beyond hematological malignancies, noting "the antineoplastic activity of proteasome inhibitors against solid tumors is poor," but does not specifically mention trials for other indications.

No information is provided about intervention models for either drug's clinical trials.