Teclistamab in the Treatment of Multiple Myeloma: Latest Updates from the 2023 EHA Annual Meeting

Letter to Editor

Ann Hematol Onco. 2023; 10(6): 1441.

Teclistamab in the Treatment of Multiple Myeloma: Latest Updates from the 2023 EHA Annual Meeting

Hao Sun1#; Xingchen Li1,2#; Lijie Han1#; Zhongxing Jiang1; Yongping Song1; Jifeng Yu3*

¹The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China

²Affiliated Hospital of Changchun University of Traditional Chinese Medicine, Changchun, Jilin, China

³Henan International Joint Laboratory of Nuclear Protein Gene Regulation, Henan University College of Medicine, Kaifeng, Henan, China

*Corresponding author: Jifeng Yu Henan International Joint Laboratory of Nuclear Protein Gene Regulation, Henan University College of Medicine, Kaifeng, Henan, China Email: Yujifengzzu@163.com

#These authors have contributed equally to this article.

Received: September 06, 2023 Accepted: October 04, 2023 Published: October 11, 2023

Abstract

As a promising novel immunotherapy modality, bispecific antibodies (BsAbs) are actively being evaluated in clinical trials for patients with hematological malignancies. Teclistamab is a T-cell-directed IgG4λ BsAb that recognizes B-Cell Maturation Antigen (BCMA) on target cells and CD3ε on T cells. As one of the promising BsAbs, teclistamab was granted orphan designations for the treatment of Multiple Myeloma (MM) in both the US and EU, the breakthrough-therapy designation for the treatment of relapsed/refractory (RRMM) by the FDA, and a Priority Medicines (PRIME) designation for the treatment of adult patients with MM who previously received ≥3 prior lines of therapy by the EMA. Recent evidence suggests that teclistamab exhibits promising efficacy and low toxicity for patients with Relapsed/Refractory Multiple Myeloma (RRMM), even at late stages. As a recently approved agent by both the FDA and the EU for adult patients with RRMM who previously received ≥3 prior lines of therapy, teclistamab is being investigated as monotherapy and in combination clinical studies in patients with MM. Here we provide an overview of the latest clinical data on teclistamab in MM presented at the 2023 European Hematology Association (EHA) annual meeting.

Keywords: Bispecific antibodies; Relapsed/refractory multiple myeloma; Teclistamab; Immunotherapy

Abbreviations: BCMA: B-Cell Maturation Antigen (BCMA); BsAbs: Bispecifc Antibodies; CD38mAb: Anti-CD38 Antibody (CD38mAb); CR: Complete Response; CRS: Cytokine Release Syndrome; IMiD: Immunomodulatory Drug; IRB: Institutional Review Board; LOT: Lines of Therapy (LOT); mDOR: Median Duration of Response (mDOR); mFU: Median Follow-up; MM: Multiple Myeloma (MM); mPFS: Median Progression Free Survival; NE: Not Estimable; ORR: Overall Response Rate; PI: Proteasome Inhibitor (PI); PRIME: Priority Medicines (PRIME); RP2R: Recommended Phase 2 Regimen; RRMM: Relapsed/Refractory Multiple Myeloma; RWPC: Real World Physician’s Choice

To the Editor

Teclistamab is being investigated as monotherapy and combined with other agents in Relapsed/Refractory Multiple Myeloma (RRMM). Recent evidence shows promising efficacy and low toxicity for patients with RRMM. Teclistamab was granted Orphan Drug designations for the treatment of RRMM in both the US and the EU [1,2]. Since then, more clinical studies have been done. Here we provide an overview of the latest clinical data on teclistamab in MM presented at the 2023 EHA annual meeting.

Teclistamab Monotherapy

The long-term follow-up from the MajesTEC-1 study in 165 patients with RRMM who received =3 prior Lines of Therapy (LOT), including a Proteasome Inhibitor (PI), an Immunomodulatory drug (IMiD) and an anti-CD38 antibody (CD38mAb), was reported [3]. After 2-year Median Follow-up (mFU), patients receiving teclistamab demonstrated deep and durable responses regardless of refractory status, with a Median Progression-Free Survival (mPFS) of 12.5 months and a Median Duration of Response (mDOR) of 24 months (not reached in patients = Com plete Response (CR). These data support teclistamab as a safe and effective off-the-shelf BCMA bispecific therapy for RRMM (Table 1). The DOR with biweekly dosing of teclistamab in 165 patients in the pivotal cohort who had received teclistamab at the recommended phase 2 dose showed that, 60/104 patients switched to Q2W dosing. At the time of switch, 49 (82%) patients achieved =CR, and 11 (18%) had a very good partial response. The median time to switch from QW to Q2W dosing was 11.1 months [4]. Prophylactic tocilizumab can reduce Cytokine Release Syndrome (CRS) risk in RRMM patients during teclistamab step-up dosing [5]. An outpatient model was reported as safe and feasible in RRMM patients with =3 lines or with prior BCMA CAR-T pre-treatment who received teclistamab step-up dosing on days 1, 3 and 8, with 6 hours’ observation in the clinic after each step-up dose administration [6]. Another study of teclistamab treatment in 12 RRMM patients with prior anti-BCMA therapy revealed that teclistamab remains effective in RRMM despite prior exposure to anti-BCMA therapies, though exposure to multiple prior anti-BCMA therapies may be predictive of diminished efficacy [7]. Teclistamab had significantly improved patient-reported outcomes over the real world physician’s choice of therapy in patients with triple-class exposed RRMM, with a positive impact on health-related quality of life in addition to significant efficacy benefits in RRMM patients [8]. In addition, teclistamab can reduce the levels of polyclonal immunoglobulins and impair the humoral immune response following vaccination. Intravenous immunoglobulin supplementation in patients with polyclonal IgG levels <4g/L should be used to prevent infections [9].

Citation: Sun H, Li X, Han L, Jiang Z, Song Y, et al. Teclistamab in the Treatment of Multiple Myeloma: Latest Updates from the 2023 EHA Annual Meeting. Ann Hematol Onco. 2023; 10(6): 1441.