Dr. Hans Lee, multiple myeloma specialist, shared with the HealthTree team a synopsis of his oral abstract for ASCO 2023. This abstract focused on the results of the completely enrolled, Phase 2 study on new BCMA targeting linvoseltamab. Learn more about this bispecific antibody below: 

What question was the clinical trial trying to answer? What phase is this trial in? 

What is the optimal dose for Linvoseltamab in relapsed/refractory multiple myeloma? 
This was a Phase 2 Trial, meaning that the drug was proven in Phase 1 to be safe for myeloma patients, and now Phase 2 can test the optimal dosing and initial efficacy. 

There were two phase 2 dose cohorts (50 mg and 200 mg), and investigators were trying to find the optimal dose for the patients. 

Simultaneously, they were trying to assess the antitumor activity as measured by overall response rate (ORR) as determined by a blinded independent central review. 

How many people participated? What were the qualifications?

• 252 myeloma patients have enrolled in this trial. 
• 104 patients were enrolled in the 50 mg cohort, 117 patients were enrolled in the 200 mg 

Note: An amendment was later made to the study allowing patients who progressed during 4-12 weeks on the 50 mg dose to escalate to 200 mg. 

Inclusion criteria: 

• Active MM by IMWG criteria 
• Progression on or after at least 3 lines of therapy, including an IMiD, a PI, and an anti-CD38 Ab, or triple refractory disease (refractory to at least 1 IMiD +1 PI + 1 anti-CD38 Ab) 

The patient population in the study included 31 patients with extramedullary disease and 67 with cytogenetic high-risk disease. The median age of patients was 66 years old (ranging between 37-90 years old). 

How long did the study last, and when was it completed?

The study began in December 2018. While the trial is still active, it’s no longer recruiting. It was last updated in early April of 2023. Patients remain under observation. 

What were the preliminary results?

Higher efficacy was observed with 200mg, including in high disease burden subgroups.
In the written abstract, the overall response rate (ORR) was 64% (200 mg cohort; n = 58, includes 12 Phase 1 patients) and 50% (50 mg cohort; n = 104).

At the time of the written abstract, the median duration of response was not reached for both cohorts (median follow-up: 2.3 months [200 mg], 4.7 months [50 mg]).

Final conclusions of the written abstract stated the 200 mg dose had consistent efficacy across high-risk subgroups and induced responses in patients who progressed on 50 mg. Safety was consistent across Phase 2 doses. The recommended linvoseltamab dose for further development was 200 mg.  

However, in the oral abstract, Dr. Hans Lee shared that at the recommended dose of 200 mg, 71% of patients achieved an Overall Response Rate (ORR) and 59% of patients achieved a Very Good Partial Response (VGPR) or better, with an 84% probability of responders to maintain response at six months. 

He also shared the responses may deepen with additional follow-up and that the median Progression-Free Survival (PFS) had not been reached. 

Across the 50 and 200 mg cohorts, 54.3% of trial patients with Complete Response (CR) or stringent Complete Response (sCR) who had evaluable samples were MRD negative at 10-5. 

Were there any complications? 

• Linvoseltamab showed a generally manageable safety and tolerability profile. 
• In the 200 mg cohort, CRS (cytokine release syndrome) was reported in 45.3% of patients, Grade 1 in 35% and Grade 2 in 9.4% of patients, and Grade 3 in 0.9% (1 patient). These kinds of responses are generally expected when using immunotherapy treatments in myeloma, so 24-hour hospitalization is required when receiving your first dosages of this medication. 

Why is this important to patients in today’s myeloma?

Anti-BCMA targeted therapies are becoming numerous in the field of multiple myeloma treatment, but that’s not a bad thing. The availability of successful “off-the-shelf” bispecific therapies is very encouraging to patients and specialists alike, who welcome more options for such a personal disease. This bispecific also shows promising results for patients that struggle to have lasting responses, such as patients with extramedullary disease and high-risk cytogenetics.

We look forward to Phase 3 Trial results of Linvoseltamab to see its efficacy against other similar therapies. 

We thank the following physicians, researchers and sponsors who made this trial possible as listed below, along with the amazing patients who participated in this trial and their supportive caregivers. 

Primary investigators: Hans C. Lee (first author)
Co-authors: Naresh Bumma, Joshua Ryan Richter, Madhav V. Dhodapkar, James E. Hoffman, Attaya Suvannasankha, Jeffrey A. Zonder, Mansi R. Shah, Suzanne Lentzsch, Joseph J. Maly, Jing Christine Ye, Ka Lung Wu, Michelle DeVeaux, Dhruti Chokshi, Anita Boyapati, Anasuya Hazra, Karen Rodriguez-Lorenc, Glenn Scott Kroog, Yariv J. Houvras, Sundar Jagannath

Organizations: 
The University of Texas MD Anderson Cancer Center, Houston, TX, The Ohio State University Comprehensive Cancer Center, Columbus, OH, Icahn School of Medicine at Mount Sinai, New York, NY, Emory University School of Medicine, Atlanta, GA, University of Miami Health System, Miami, FL, Indiana University Simon Cancer Center and Roudebush VAMC, Indianapolis, IN, Karmanos Cancer Institute, Detroit, MI, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, Columbia University Medical Center, New York, NY, Norton Cancer Institute, Louisville, KY, University of Michigan, Ann Arbor, MI, Ziekenhuis Netwerk Antwerpen Stuivenberg, Antwerp, Belgium, Regeneron Pharmaceuticals, Inc., Tarrytown, NY