P-024: Early outcomes and therapy modification strategies in Multiple Myeloma patients treated with teclistamab, CD3XBCMA BITE; a single center experience.

Introduction: Cellular therapies in Multiple Myeloma have gained attention in recent years with the first commercially available Bispecific T-cell Engaging Monoclonal Antibody (BITE), CD3XBCMA teclistamab being approved for use for patients with relapsed disease following four or more lines of prior therapy in 2022. The impact of early treatment frequency modification as well as predictive immune markers of response are incompletely understood in this patient population. We aimed to assess and characterize early responses to teclistamab in our patient population as well as understand genomic profiling related mutations identifiable through commercially available assays in predicting treatment response.

Methods: Nine patients who were treated at our health center with teclistamab between November 2022 and February 2023 were included in this analysis. Patients’ baseline characteristics, markers of disease response including hematologic, bone marrow molecular, evaluable minimal residual disease (MRD) at three months post dose escalation completion were abstracted. ClonoSEQ ® and Tempus xT ® 648 gene DNA NGS panel were utilized for MRD tracking and genomic profiling respectively.

Results: The median age of the patient population was 75 years (41-81) and the median number of prior lines being 6(4-9). 3 patients had IMWG defined high risk FISH abnormalities and 2 patients had EMP prior to therapy. Mean Absolute Lymphocyte Count prior to therapy was 1.16 (x10^3/ul). 7 patients had cytokine release syndrome (CRS) event while 1 patient had immune effector cell related neurotoxicity (ICANS) event. None of the CRS or ICANS events were grade 3 or higher. Mean absolute CD4 count and CD8 count prior to therapy was 550/cu mm and 622/cu mm. At the 3-moth evaluation, 3 patients had achieved a CR, with 2 being stringent CR, MRD- . 1 VGPR, 2 PR and 3 PD were also observed. Of the 3 patients with CR, 2 patients were treated with Q2 weekly dosing immediately following the dose escalation cycle due to patient tolerance issues, one of whom had also achieved a stringent CR. Amongst all patients with response at the 3-month bone marrow evaluation, 1 patient had DNA damage related mutation (CHEK2) whilst 2 had residual CHIP mutations (TET2 and DNMT3A) with prior exposure to multi-agent antineoplastic therapy (DNA damage agents).

Conclusions: In our limited patient dataset, 6 (66.7%) patients had achieved an early best response of PR or higher, consistent with clinical trial data. Despite treatment frequency modification, two patients achieved a CR with one patient achieving a stringent CR at the 3-month evaluation. Further studies are needed to assess response adapted treatment frequency modification as well as study genomic perturbations that can alter the function of immune cells (T cells) and impact response to BITE.