Physician Dana Farber Cancer Institute Boston, Massachusetts, United States
Introduction: Teclistamab is a bispecific t-cell engaging (BiTE) therapy that was approved by the US FDA in October 2022 for treatment of relapsed and refractory multiple myeloma (RRMM) in patients who have received ≥ 4 lines of therapy. We report our initial experience with commercial teclistamab use at the Dana-Farber Cancer Institute/Brigham and Women’s Hospital.
Methods: Patients treated with teclistamab until April 15, 2023 were included in the analysis. Data was collected for baseline demographics, prior therapies, efficacy including response rates (ORR), and safety variables such as rates of cytokine release syndrome (CRS), neurological toxicity (NT), cytopenias and infectious complications.
Results: 34 patients were treated with teclistamab from December 15, 2022 to April 15, 2023. The median age was 65 (range 51-83), with 10 females (29%) and 24 males (71%). Median prior lines of therapy was 6 (range 4-12) with 55% of patients having had a prior stem cell transplant. Seven patients (21%) had received prior BCMA-directed CAR-T therapy and 10 (29%) had received prior BCMA-targeting antibody-drug conjugate therapy. Twenty-one patients (62%) had at least one high-risk (HR) cytogenetic risk factor among del 17p, t(4;14), t(14;16) or 1q21 gain or amplification with breakdown as follows: 1 HR factor: 11 (32%), 2 HR factors: 9 (26%), 3 HR factors: 1 (3%). Eight patients (24%) had a creatinine clearance < 40 ml/min. Thirteen patients (38%) treated had extramedullary disease (EMD) and 5 (15%) had CNS involvement. Hematologic toxicity included anemia (n=34, 100%, grade ≥3; 62%), neutropenia (n=24, 71%, grade ≥3; 47%), and thrombocytopenia (n=31, 91%, grade ≥3; 53%) with most present prior to treatment. CRS was reported in 19 patients (56%), 12 with grade 1 (35%), 7 with grade 2 (21%) and none with grade 3 or higher. Tocilizumab was used in 8 patients (24%) and dexamethasone was used in 4 patients (12%). Grade 1 neurotoxicity was assessed in 1 patient (3%), which did not require treatment. Eleven (32%) infectious complications were observed with 3 (9%) patients presenting with grade 3 or greater infections requiring hospitalization or urgent intervention, all non-fatal. At a median follow-up of 6 weeks, ORR is 44%, with 3 patients (9%) achieving a complete response (CR), and 10 (29%) achieving VGPR or greater. Thirteen patients have had disease progression or died at the time of data cut-off (38%). The ORRs of those with renal dysfunction (CrCl < 40 ml/min), EMD or ≥1 HR cytogenetic risk factor is 25%, 23% and 48%, respectively. ORR in patients with prior BCMA-targeted therapy exposure is 27%.
Conclusions: Overall, we observed that teclistamab treatment in a commercial setting generated comparable responses to the previously reported clinical trials without any new toxicity signals. While additional follow up with commercial Teclistamab use in the real-world is needed to validate these results, this study reveals the need for efficacious therapies in high-risk or ultra-high-risk disease.