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    Cellular and T cell engager Immunotherapy

    Category: Cellular and T cell engager Immunotherapy

    Debulking Chemotherapy Abrogates the Risk of Non-Response in Multiple Myeloma Patients with High Tumor Burden Receiving Teclistamab

    (PA-089) Debulking Chemotherapy Abrogates the Risk of Non-Response in Multiple Myeloma Patients with High Tumor Burden Receiving Teclistamab

    Friday, September 19, 2025
    Introduction: Teclistamab (tec) is highly effective for heavily pre-treated multiple myeloma (MM) patients (pts), yet nearly 30-40% of pts fail to respond. Extramedullary disease, ISS stage, high marrow burden, and high soluble BCMA have been identified as markers of poor response in clinical trials. Here we explore whether debulking chemotherapy can successfully lower tumor burden and improve outcomes with tec.

    Methods: This was a retrospective study in relapsed refractory MM pts who received tec outside clinical trials from 11/2023-04/025. Debulking chemo, either D-PACE (dexamethasone, cisplatin, doxorubicin, cyclophosphamide and etoposide) or high-dose melphalan (HD-Mel), were administered to selected patients at the discretion of treating physician to reduce tumor burden prior to initiating tec. High myeloma disease burden (Hi-MM) was defined by presence of any of the following: extramedullary disease, ≥50% bone marrow plasmacytosis, secondary plasma cell leukemia, or need for transfusion support prior to initiating therapy, and was determined both pre-chemo (if applicable) and pre-tec. Primary outcome was overall response rate (ORR) to tec, with PFS and OS as secondary outcomes.

    Results:

    35 pts were treated with tec; median age was 67 (range 48-90) years and 51% were male. Patients received a median of 5(range 3-11) prior lines of therapies, with 100% triple class refractory, 31.4% penta-drug refractory and 20% had prior anti-BCMA therapy exposure. 19 (54.3%) patients received debulking chemo: DPACE in 16, HD-Mel in 3. Hi-MM was present in 10/35 (28.6%) of patients prior to tec. ORR was significantly inferior in patients with Hi-MM prior to tec (2/10, 10%) compared to patients without Hi-MM (24/25, 96%, p < 0.001). Among pts who underwent chemo for Hi-MM, ORR to tec was 79% (15/19). All pts who responded to chemo and were no longer Hi-MM responded to tec (12/12, 100%), including all 4 pts who were primary refractory to a BCMA bispecific in the line prior to chemo. Patients with Hi-MM who did not receive chemo responded poorly to tec (2/6; 33.3%). Hi-MM was the only factor predicting response to tec (OR 0.01; 95% CI 0.01-0.09, p</em>< 0.001) with no impact of any other pt or disease-related factor. At a median follow up of 6.9 months, pts with Hi-MM vs those without had inferior PFS (2.1 vs 10.6 months; p < 0.001) and OS (3.7 vs NR,p< 0.001). Pts with Hi-MM who underwent chemo prior to tec had similar PFS and OS to pts without Hi-MM.  Hi-MM prior to tec was the only significant factor impacting survival outcomes (PFS:HR 16.83 (4.41, 64.18), p< 0.001); OS: HR 10.69 (2.52, 45.27), p</em>=0.001).


    Conclusions:

    High tumor burden was the major determining factor for response rates and survival outcomes after tec therapy, with response in 96% of pts without high burden. Pts with high burden who received debulking chemo had similar ORR, PFS, and OS to pts without high burden, with chemo abrogating the risk of non-response in pts with historically very poor responses.