Real-world descriptive analysis of the use of bispecific t cell engagers (BiTEs) in the treatment of hematological malignancies in Qatar: A state-wide retrospective cohort study Free

Introduction

One of the most promising modalities in immunotherapy includes Bispecific T cell Engagers (BiTEs), a class of engineered antibodies that are specifically tailored to redirect T-cells against neoplastic cells to elicit vigorous cytotoxic responses independent of major histocompatibility complex restriction. BiTEs simultaneously bind to a surface antigen on T cells, typically CD3, and a tumor-associated antigen to create a bridge that activates T-cells and facilitates the target cancer cell killing (Einsele et al., 2020). This new approach has great potential for patients with relapsed and/or refractory (r/r) diseases, where conventional therapies have been unsuccessful (Weber, Maus and Mackall, 2020). Bispecific antibody has different indications in hematological malignancies, blinatumomab treating CD19 positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second remission with measurable minimal residual disease (MRD) and r/r disease. Nevertheless, in r/r multiple myeloma (MM) elranatamab and teclistamab have been used to target BCMA. Another BiTE targeting CD20 used in r/r follicular lymphoma (FL) such as mosunetuzumab, and glofitamab in r/r diffuse large B cell lymphoma (DLBCL), while epcoritamab has been approved in both indications (Shouse G., 2025). This study aims to present Real World Data on the efficacy and Safety of BiTE's to treat hematological malignancy in Qatar.

Method

This is a descriptive retrospective cohort study, including all adult hematological patients who were treated with BiTEs: epcoritamab, glofitamab, blinatumomab, and teclistamab. All patients from June 2021 till the end of May 2025 who were treated in Qatar was reviewed. All patients were previously treated with chemotherapy. To evaluate the efficacy, we calculated the objective response rate (ORR): (as the sum of the complete response (CR) and the partial response (PR)). In addition to stable disease (SD), disease progression (DP), duration of response (DoR), time to response (TTR), progression free survival (PFS), and 12 months over all survival (OS). Clinical response was evaluated at interim response. Adverse drug reactions (ADRs) were reported using the National Cancer Institute's Common Terminology Criteria for Adverse Events.

Results

The study included a total of 27 patients, 24/27 patients were included in the analysis, and the median age at BiTE start was 43 years (interquartile range 14-87). Most were males 79%. The majority of patients were diagnosed with ALL 15/24 (63%). Added to DLBCL 4/24 (17%), MM 3/24 (13%), Burkitt Lymphoma and Primary Mediastinal Large B cell lymphoma 1/24 (4%) for each. All patients had ECOG performance of 1 or more. BiTEs were used post chemotherapy, and the median number of prior therapy lines were 2 (1-8). The most common BiTE used was: blinatumomab 16/24 (67%). Then, teclistamab 3/24 (13%), glofitamab 3/24(13%), and epocoritamab 2/24(8%). The indication of therapy varied between relapsed refractory disease, and as consolidation due to intolerance to chemotherapy, adding to bridging to stem cell transplantation (non-FDA approved indication).

Out of 24 patients, twelve had a favorable response yielding an ORR of 50%, with CR in 10 (41%) and PR 2 (8%). Mean DoR is 7 months (95% CI, 0.76 – 35.8), PFS is 4.6 months (95% CI, 2.7-6.5), median TTR is 4.5 months (95% CI, 3.2-6), and 12-months OS is 50%. Regarding the safety and tolerability of the medications, almost all patients 23/24 (96%) had adverse events during their treatment cycles. A Total of 130 ADRs were reported. The most common ADR was lymphopenia 18/24 (75%) and anemia 17/24 (71%), Cytokine release syndrome (CRS) 10/24 (42%); where 1/10 had grade 4 and died. Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) grade 2-4 has been reported in 3/24 (13%). Many other SE were reported.

Conclusion

This retrospective cohort study provides a real-world utilization perception of BiTEs in treating hematological malignancies in Qatar. Despite the small sample size and the study design, our findings nearly comply with primary literature that BiTEs serve as a promising therapeutic alternative for patients with relapsed or refractory disease, particularly those who have exhausted other modalities. However, the high incidence of reported adverse drug reactions (ADRs), including severe toxicities such as CRS and ICANS, highlights the need for robust and careful strategies for safety and tolerability assessment.