CD8 effector T cells enhance teclistamab response in BCMA-exposed and -naïve multiple myeloma

Firestone, Ross S.; McAvoy, Devin; Shekarkhand, Tala; Serrano, Edith; Hamadeh, Issam; Wang, Alice; Zhu, Menglei; Qin, Wei Ge; Patel, Dhwani; Tan, Carlyn R.; Hultcrantz, Malin; Mailankody, Sham; Hassoun, Hani; Shah, Urvi S.; Korde, Neha; Maclachlan, Kylee H.; Landau, Heather J.; Scordo, Michael; Shah, Gunjan L.; Lahoud, Oscar B.; Giralt, Sergio; Murata, Kazunori; Hosszu, Kinga K.; Chung, David J.; Lesokhin, Alexander M.; Usmani, Saad Z.

doi:10.1182/bloodadvances.2023011225

Cited by 14 publications

(5 citation statements)

References 47 publications

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“…In our relatively short period of follow-up, the response rates are similar in this heavily pre-treated population compared to those seen in clinical trials. Continued analysis will include the timing of tocilizumab due to the incidence of CRS after the first teclistamab step-up dose and long-term disease response due to reports of a correlation between an early immune response including CRS during step-up dosing and treatment outcomes [4]. In conclusion, these data support the efficacy of early incorporation of prophylactic tocilizumab through prevention of severe CRS as well as a path to safely administer teclistamab in the outpatient setting.…”

Section: Dear Editormentioning

confidence: 75%

Prophylactic tocilizumab to prevent cytokine release syndrome (CRS) with teclistamab: A single-center experience

Scott,

Marin,

Maples

et al. 2023

Blood Cancer J.

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Section: Dear Editormentioning

confidence: 75%

Prophylactic tocilizumab to prevent cytokine release syndrome (CRS) with teclistamab: A single-center experience

Scott,

Marin,

Maples

et al. 2023

Blood Cancer J.

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“…From a biological perspective, this observation suggests either T-cell anergy or BCMA antigen loss in the T-cell redirection therapy exposed cohort since CRS is merely a manifestation but not a cause of T-cell activation. 14 Interestingly, the presence of high-risk cytogenetic risk features also resulted in significantly lower rates of CRS; whether this finding is secondary to the reduced efficacy of Tec is an area that warrants further investigation.…”

Section: Discussionmentioning

confidence: 99%

Patterns of CRS with teclistamab in relapsed/refractory multiple myeloma with or without prior T-cell redirection therapy

Hamadeh,

Shekarkhand,

Rueda

et al. 2024

Blood Advances

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Teclistamab (Tec) is a first-in-class BCMA X CD3 bispecific T-cell engager antibody approved for treating multiple myeloma progressing after at least 4 lines of therapy. The objective of this study was to evaluate the rate of cytokine release syndrome (CRS) in patients who were treated with commercial Tec and had prior exposure to other T-cell redirection therapies. A retrospective chart review was performed to identify patients who completed the Tec step-up dosing phase between November 2022 and November 2023. Patients were divided into 2 cohorts based on prior exposure to T-cell redirection therapy (cohort 1: T-cell redirection therapy experienced; cohort 2: T-cell redirection therapy naïve). The primary objective was to compare the differences in the rates of CRS between the two cohorts. Univariate and multivariate logistic regression analyses were performed to assess the association between CRS rates with Tec and prior treatment with T-cell redirection therapy. A total of 72 patients were included in the analysis (27 in cohort 1 and 45 in cohort 2). The CRS rates were significantly lower in cohort 1 (37%, n=10) compared to cohort 2 (80%, n=36; p=0.0004). Based on multivariate logistic regression analysis, patients without prior exposure to T-cell redirection therapy (cohort 2) had about a 4-fold increase in the incidence of CRS (95% CI: 1.40-14.90, p=0.0002) with Tec. In our study, prior exposure to T-cell redirection therapy reduced the risk of CRS with Tec during the step-up dosing phase. This observation will allow for the optimization of CRS prophylactic strategies for Tec.

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“…60 In another analysis of patients with MM treated with teclistamab, a higher proportion of effector memory T cells and lower proportion of Tregs correlated with improved response to therapy. 61 Together, these studies suggest that the clinical response to TCEs may be affected by the preexisting properties of T cells. Some of the features relating to tumor burden including advanced stage, presence of extramedullary disease, as well as excess soluble ligand (such as soluble BCMA), potentially providing a “sink effect,” may also affect outcomes in patients treated with TCEs.…”

Section: Immune Correlates Of Response After T-cell Redirection In MMmentioning

confidence: 95%

Immune status and selection of patients for immunotherapy in myeloma: a proposal

Dhodapkar

2024

Blood Advances

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Newer immune-based approaches based on recruitment and redirection of endogenous and/or synthetic immunity such as chimeric antigen-receptor-T (CAR-T) cells or bispecific antibodies are transforming the clinical management of multiple myeloma (MM). Contributions of the immune system to the anti-tumor effects of myeloma therapies are also increasingly appreciated. Clinical malignancy in MM originates in the setting of systemic immune alterations that begin early in myelomagenesis and regional changes in immunity impacted by spatial contexture. Pre-existing and therapy-induced changes in immune cells correlate with outcomes in MM patients including following immune therapies. Here we discuss insights from and limitation of current data about immune status and outcomes following immune therapies in MM patients. Pre-existing variation in systemic and/or regional immunity is emerging as a major determinant of the efficacy of current immune therapies as well as vaccines. MM is however a multifocal malignancy. As with solid tumors, integrating spatial aspects of the tumor and consideration of immune targets with biology of immune cells may be critical to optimize the application of immune therapy including T cell redirection in MM. We propose 5 distinct spatial immune types of MM- immune-depleted, immune-permissive, immune-excluded, immune-suppressed, and immune-resistant, that may provide an initial framework for optimal application of specific immune therapies in MM. Such considerations may also help optimize rational patient selection for emerging immune therapies to improve outcomes.

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CD8 effector T cells enhance teclistamab response in BCMA-exposed and -naïve multiple myeloma

Cited by 14 publications

References 47 publications

Prophylactic tocilizumab to prevent cytokine release syndrome (CRS) with teclistamab: A single-center experience

Prophylactic tocilizumab to prevent cytokine release syndrome (CRS) with teclistamab: A single-center experience

Patterns of CRS with teclistamab in relapsed/refractory multiple myeloma with or without prior T-cell redirection therapy

Immune status and selection of patients for immunotherapy in myeloma: a proposal

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