Dr Lee on the Significance of Longer-Term Data for Linvoseltamab in R/R Multiple Myeloma

Hans C. Lee, MD, associate professor, Department of Lymphoma/Myeloma, Multiple Myeloma Clinical Research, Department of Lymphoma/Myeloma, Division of Cancer Medicine, the University of Texas MD Anderson Cancer Center, discusses how longer-term efficacy and safety data with linvoseltamab (REGN5458) derived from the phase 2 LINKER-MM1 study (NCT03761108) may potentially impact treatment approaches in relapsed/refractory multiple myeloma.

The study investigated linvoseltamab, a BCMA/CD3-directed bispecific antibody, in a heavily pretreated patient population with relapsed/refractory multiple myeloma which demonstrated promising results in terms of efficacy and safety. The dose escalation/expansion study enrolled patients who had progressed on multiple lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, or who were triple-class refractory.

Patients enrolled onto the dose-expansion portion of the study underwent step-up dosing with linvoseltamab, followed by a 24-hour hospitalization period, Lee details. The weekly step-up dosing regimen, starting with 5 mg on day 1 and 25 mg on day 8, differentiated linvoseltamab from other treatments. During the initial 3 treatment cycles, patients were administered 200 mg of linvoseltamab once weekly. Subsequently, in cycles 4 and 5, the dosage was modified to 200 mg every 2 weeks. Starting from cycle 6, patients achieving a very good partial response (VGPR) or higher received the agent at a dosage of 200 mg every 4 weeks. Those who did not achieve a VGPR continued to receive the agent at a dosage of 200 mg every 2 weeks. This weekly step-up dosing regimen  was a notable distinguishing feature of linvoseltamab, Lee notes.

Long-term data from the study presented at the 

, showed high response rates with linvoseltamab, with an overall response rate (ORR) of 69% at a median follow-up of 8.1 months, Lee reports. Furthermore, the median duration of response and progression-free survival (PFS) were not reached, with estimated 9-month rates of 86.8% and 72.8%, respectively. Importantly, linvoseltamab exhibited a generally manageable toxicity profile with no new safety signals identified.

Additional data from the LINKER-MM1 study, published later in 2023, demonstrated even higher ORR of 71% as adjudicated by an independent review committee and a complete response rate of 46% at an 11-month median follow-up, Lee reports. These findings suggest that linvoseltamab shows continued efficacy, durability of responses, and encouraging safety signals in relapsed/refractory multiple myeloma, Lee explains.

The rapid de-escalation of dosing frequency, limited hospitalization requirements for cytokine release syndrome (CRS) monitoring, and low CRS rates make linvoseltamab a promising approach for the treatment of patients with relapsed/refractory multiple myeloma, Lee concludes.

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Hans C. Lee, MD, discusses the significance of longer-term data for linvoseltamab from the LINKER-MM1 study in relapsed/refractory multiple myeloma. 

Dr Lee on the Updated Efficacy and Safety Data for Linvoseltamab in R/R Multiple Myeloma

Hans C. Lee, MD, associate professor, Department of Lymphoma/Myeloma, Multiple Myeloma Clinical Research, Department of Lymphoma/Myeloma, Division of Cancer Medicine, the University of Texas MD Anderson Cancer Center, discusses updated data from the phase 2 LINKER-MM1 study (NCT03761108) investigating the BCMA/CD3-directed bispecific antibody linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma.

The first-in-human, dose escalation/expansion study enrolled heavily pretreated patients who had either progressed on or after 3 or more lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, or patients who were triple-class refractory. In the dose-expansion portion of the investigation, participants underwent step-up dosing with linvoseltamab, receiving 5 mg on day 1 and 25 mg on day 8, followed by a 24-hour hospitalization period. For the first 3 treatment cycles, patients received 200 mg of linvoseltamab once a week. In cycles 4 and 5, the dosage was adjusted to 200 mg every 2 weeks. From cycle 6 onward, individuals achieving a very good partial response (VGPR) or higher received the agent at 200 mg every 4 weeks. Patients whose disease did not attain a VGPR continued to receive the agent at 200 mg every 2 weeks.

Long-term data from the study were presented at the 

. At a median follow-up of 8.1 months, responses with linvoseltamab remained effective and had deepened since the prior analysis at a median follow-up of 5.6 months, Lee reports. At the recommended dose of 200 mg, the agent produced an overall response rate (ORR) of 69%, Lee adds, 59% of which were VGPRs or higher and 39% of which were complete responses (CRs). Of those who achieved a CR or sCR with available minimal residual disease data, 59% did not show measurable residual disease.

Additionally, the median time to response with linvoseltamab was 1 month. The median duration of response and PFS was not reached, although estimated 9-month rates were 86.8% and 72.8%, respectively.

Regarding safety, linvoseltamab had a generally manageable toxicity profile with no new safety signals at the time of follow-up, Lee states. Overall, these data show that linvoseltamab produces early, durable, and high responses in pretreated patients with relapsed/refractory multiple myeloma, supporting the agent's ongoing investigation in the phase 3 LINKER-MM3 trial (NCT05730036).

Hans C. Lee, MD, discusses updated data from the phase 2 LINKER-MM1 study evaluating linvoseltamab in patients with relapsed/refractory multiple myeloma.

Hans C. Lee, MD, associate professor, Department of Lymphoma/Myeloma, Multiple Myeloma Clinical Research, Department of Lymphoma/Myeloma, Division of Cancer Medicine, the University of Texas MD Anderson Cancer Center, discusses the investigation of the BCMA x CD3 bispecific antibody linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma.

investigators presented findings from the phase 2 LINKER-MM1 study (NCT03761108) on the use of linvoseltamab

, which was explored at 2 given doses. In the 50-mg cohort (n = 104), the overall response rate (ORR) was 50%, including a stringent complete response (sCR) rate of 14% and a complete response (CR) rate of 7%. In the 200-mg cohort (n = 117), the ORR was 71%, including sCR and CR rates of 16% and 14%, respectively.

Within both treatment arms, step-up dosing was used with 5 mg of linvoseltamab given on day 1 and 25 mg given on day 8. Patients then continued with 50 mg or 200 mg from week 3 on.

Notably, the majority of patients who were included in the 200-mg cohort remained on the study at the time of data cutoff of February 2023, Lee continues. Among patients with a sCR across both the 50-mg and 200-mg cohorts who had evaluable MRD data (n = 54), 54.3% of patients were MRD-negative at a 10-5 sensitivity.

In terms of duration, responses appeared to be durable and deepened with time, Lee adds. The 6-month probability of maintaining a response in the 200-mg cohort was 83.6%, and the 12-month probability was 79.2%. In the 50-mg cohort, the median progression-free survival (PFS) was 7.9 month (95% CI, 2.1-12.9), and in the 200-mg cohort, the median PFS had not been reached. The estimated 6-month PFS rates in the 50-mg and 200-mg cohorts were 54.6% and 72.7%, respectively.

Hans C. Lee, MD, discusses the investigation of the BCMA x CD3 bispecific antibody linvoseltamab in patients with relapsed/refractory multiple myeloma.


Hans C. Lee, MD

Articles

Dr Lee on the Significance of Longer-Term Data for Linvoseltamab in R/R Multiple Myeloma

Dr Lee on the Updated Efficacy and Safety Data for Linvoseltamab in R/R Multiple Myeloma

Dr Lee on the Investigation of Linvoseltamab in Relapsed/Refractory Multiple Myeloma