Real-World Patient Characteristics and Outcomes in Patients with High-Risk Cytogenetic Relapsed or Refractory Multiple Myeloma Receiving Teclistamab across Community Oncology Practices in the US
Authors: Dhakal Binod , Kim Nina , John William , Wu Bingcao , Lucht Sarah , Lin Dee , Bland Emily , Paner-Straseviciute Agne , Van Doren Bryce , Hester Laura , Giegerich Sarah , Fowler Jessica , Gash Yul Brian , Walker Sian , Klink Andrew , Hearty Christina , Feinberg Bruce , Marshall Alexander , Doyle Margaret , Voorhees Peter M. 
Published: December 2024

Background
Teclistamab, a first-in-class B-cell maturation antigen (BCMA) x CD3 bispecific antibody, gained US regulatory approval for relapsed or refractory multiple myeloma (MM) in Oct 2022 based on the MajesTEC-1 trial. Real-world patients (pts) with MM receiving teclistamab may differ from trial participants and be ineligible for clinical trials. We sought to evaluate patient profiles, treatment patterns, and outcomes in pts with MM who had high-risk cytogenetic abnormalities and received teclistamab in real-world settings in the US.
Methods
This was a retrospective US multi-site chart review. Participating physicians from Cardinal Health's Oncology Provider Extended Network abstracted data from electronic medical charts of eligible pts. Eligible pts with MM (≥18 years) initiated teclistamab on or after 10/25/22 and had a minimum 1-month follow-up at time of data abstraction (3/11/24); pts receiving teclistamab as part of a clinical trial were excluded. Pts were indexed on the first teclistamab dose. Characteristics and treatment history were captured during the pre-index baseline period; cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were captured during the step-up dosing (SUD) period; infections and clinical outcomes were captured during the follow-up period. Variables were analyzed descriptively. This analysis reports only on a subgroup of pts with observed presence of high-risk cytogenetics at initial MM diagnosis, defined as t(4;14), t(14;16), t(14;20), del(17p), gain(1q21), or amp(1q21) (‘high-risk‘).
Results
Thirty-eight high-risk pts were identified out of a total sample of 101 pts. Median age at teclistamab initiation was 66 years (range: 56-84); 63% male; 74% White, 18% Black, and 92% non-Hispanic; 53% had commercial and/or Medicare Advantage and 24% had Medicare Fee-For-Service insurance.
Of the 38 pts with high-risk cytogenetics, 34 (90%) had an ECOG score 0-1 at time of teclistamab initiation and 23 (61%) had known stage III Revised International Staging System (R-ISS) at initial MM diagnosis. Relevant baseline comorbidities included anemia (32%) and renal impairment or failure (11%). 5 pts (13%) had an observed presence of extramedullary plasmacytoma and most (71%) had presence of lytic bone lesions on imaging at initiation. Pts had a median of 4 (range: 2-13) prior lines of therapy. Prior to teclistamab initiation, 5 pts (13%) had been treated with other BCMA-targeted therapies (all CAR-T therapy). Among pts with prior anti-BCMA therapy exposure, the median time from last anti-BCMA therapy to teclistamab initiation was 9.9 months (range: 4.0-41.8).
During the SUD period, 14 (37%) pts experienced CRS, all grades 1-2, and 4 (11%) experienced ICANS, majority (75%) of which were grade 1-2. No pts discontinued teclistamab due to CRS or ICANS.
At a median follow-up of 4.0 months (range: 0.9-15.1), 10 (26%) high-risk pts developed infections while on teclistamab. Immunoglobulin (IVIG) as primary prophylaxis for infection was administered to 17 (45%) of high-risk pts; of these pts, 15 (88%) reported an IgG level &lt;400 mg/dL prior to IVIG administration. In this high-risk population, 2 (5%) pts were hospitalized and no pts discontinued teclistamab due to infections. The overall response rate (ORR) was 74% among pts with high-risk cytogenetics. The estimated progression-free survival (PFS) rate at 6 months post teclistamab initiation was 79%.
Conclusion
In this interim analysis of an ongoing, physician-led chart review study in the US, we evaluated a subset of pts who were observed to have high-risk cytogenetic abnormalities, a population broadly considered as hard-to-treat in the real world. Despite these high-risk features and heavy pre-treatment, high ORR and estimated 6-month PFS rate were observed in this real-world population. CRS and ICANS rates and severity appeared similar to existing literature on real-world teclistamab-recipients, with no pts discontinuing teclistamab due to CRS or ICANS. While updated results with longer follow-up are warranted, the preliminary findings suggest that teclistamab is an effective and safe treatment option for pts with high-risk relapsed/refractory MM.