Early Linvoseltamab Use Prevents Myeloma Progression: Paula Rodríguez-Otero, MD, PhD

At the 22nd International Myeloma Society annual meeting today, Paula Rodríguez-Otero, MD, PhD, presented late-breaking data from the phase 2 LINKER-SMM1 trial (NCT05955508), which is currently investigating the safety and efficacy of linvoseltamab in patients with high-risk smoldering multiple myeloma. The research from her and her team, “Safety and Efficacy of Linvoseltamab (LINVO) in Patients (Pts) With High-Risk Smoldering Multiple Myeloma (HR-SMM): First Results From the Phase 2 LINKER-SMM1 Trial,” shows promising results: a 100% overall response rate, 74% achieving a very good partial response or better after 1 treatment cycle, and 37% reaching a complete response or better.

Rodríguez-Otero is medical coordinator of the Central Unit for Clinical Trials; associate clinical professor, preclinical and hematology seminars; and deputy director of the expert degree in immuno-oncology, School of Medicine, Cancer Center Clínica Universidad de Navarra (University of Navarra) in Pamplona, Spain.

This transcript has been lightly edited for clarity; captions were auto-generated.

Transcript

Can you give us a brief background on the LINKER-SMM1 trial: patient population, outcomes of interest, and results you would like to highlight?

The LINKER-SMM1 trial is a phase 2 study that is aiming to evaluate the efficacy and safety of linvoseltamab, which is a BCMA bispecific antibody, in patients with high-risk smoldering multiple myeloma. Linvoseltamab is already a well-known drug; it is a bispecific antibody targeting BCMA that has been approved in the setting of triple class–exposed relapsed/refractory multiple myeloma, inducing a high overall response rate and deep, durable responses.

The pivotal study that led to the approval of linvoseltamab is called the LINKER-MM1 study.

In this trial, we aim to show that in the setting of high-risk smoldering multiple myeloma, early intervention with this drug could potentially significantly delay or prevent the progression to active disease. In this study, we aim to enroll 40 patients with smoldering multiple myeloma diagnosed within 5 years of study entry and meeting high-risk features either by Mayo 2018 "20-2-20" criteria or PETHEMA criteria [Programa de Estudio y Tratamiento de las Hemopatias Malignas].

The study has 2 parts. In part 1, there is a safety run-in phase that enrolled 6 patients. The primary end point of this phase is to evaluate the safety of the treatment. Then there is an expansion phase that will enroll 34 patients. The primary end point of this part 2 expansion phase is complete response rate and MRD [minimal residual disease] activity at 1 year and 2 years. Linvoseltamab is given using a step-up dosing phase with lower doses compared to the approved schedule. One mg on week 1, 4 mg on week 2, then 25 mg on week 3, followed by the recommended dose of linvoseltamab, which is 200 mg every month. Patients will receive 2 years of treatment, then the treatment will be stopped and the patient will start a post-treatment follow-up phase.

So far, 24 patients have been enrolled and treated, all of them meeting the criteria of high-risk smoldering multiple myeloma. Eleven patients using the Mayo criteria and 6 patients using the PETHEMA criteria.

The treatment is still ongoing.

Regarding the safety profile, in general, we see a much more favorable safety profile in this population of smoldering multiple myeloma as compared to the population of triple-class–exposed relapsed/refractory. Regarding hematological toxicity, we do see some degree of neutropenia. Forty-six percent of the patients will develop any-grade neutropenia, but only 25% grade 3 or 4, [with] a limited incidence of cytokine release syndrome, 42% of the patients, but all of the events were grade 1 except for one single grade 2 event. We haven't seen any ICANS [immune effector cell–associated neurotoxicity syndrome] events as yet. We also see a significantly lower incidence of severe infections; only 12% of the patients had a grade 3 infection, so no grade 4 events and no discontinuations related to adverse events. Immunoglobulin replacement was given consistently to 95% of the patients in the study.

Regarding the efficacy, we do see a higher overall response rate. Indeed, all evaluable patients for response, which is 19 out of 24, achieved an objective response, and we do see responses deepening over time. For example, in the safety run-in phase, which is the cohort with the longest follow-up, the complete response rate is 83%. Overall, we do see a safety profile, which is more favorable than the safety profile observed in relapsed/refractory myeloma, and a high overall response rate, with these responses deepening over time.

We believe that this ongoing study will provide evidence that may support the use of linvoseltamab in this high-risk smoldering population in order to either delay or even prevent the progression to active disease.