Abstract: Diffuse Large B-Cell Lymphoma (DLBCL) is a heterogeneous malignancy associated with significant morbidity and mortality. Orelabrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, has shown promise as a therapeutic agent in DLBCL treatment. This retrospective analysis aims to evaluate the efficacy and safety of Orelabrutinib-based regimens in DLBCL management. Nineteen patients diagnosed with DLBCL were included in the study, treated between August 2020 and August 2022. Diagnostic modalities included biopsies, next-generation sequencing, immunohistochemistry, and PET/CT scans. Treatment regimens comprised Orelabrutinib combined with chemotherapy or immunotherapy, guided by NCCN or CSCO guidelines. The study demonstrated a high overall response rate (ORR) of 89.5%, with favorable survival outcomes. Adverse events such as neutropenia and anemia were notable but manageable. This retrospective analysis suggests that Orelabrutinib-based regimens hold promise as an effective treatment option for DLBCL, warranting further investigation.Introduction
Diffuse Large B-Cell Lymphoma (DLBCL) presents a significant therapeutic challenge due to its aggressive behavior and diverse clinical manifestations. In recent years, there has been a growing interest in exploring novel treatment modalities to enhance outcomes for patients with DLBCL. Orelabrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, has emerged as a promising candidate for DLBCL therapy. This article presents a comprehensive retrospective analysis evaluating the efficacy and safety of Orelabrutinib-based regimens in the treatment of DLBCL.
Study Methods: The retrospective study was conducted at a single center and included 19 patients diagnosed with DLBCL, who were treated between August 2020 and August 2022. Patient selection was based on the 2016 World Health Organization (WHO) criteria for DLBCL. Diagnostic workup encompassed a range of techniques including biopsies, next-generation sequencing, immunohistochemistry, and PET/CT scans to ensure accurate diagnosis and staging. Additionally, comprehensive ethical clearance was obtained, and informed consent was secured from all patients involved in the study.
Results:
The retrospective analysis of Orelabrutinib-based regimens in the treatment of Diffuse Large B-Cell Lymphoma (DLBCL) yielded insightful findings regarding treatment efficacy and patient outcomes. Among the 19 patients included in the study, a comprehensive evaluation of treatment response and survival outcomes was conducted, revealing notable results.
Overall Response Rate (ORR): The analysis demonstrated a high overall response rate (ORR) of 89.5% among patients treated with Orelabrutinib-based regimens. This indicates that the majority of patients experienced a reduction in tumor burden or disease stabilization following treatment initiation. The ORR reflects the combined rates of complete response (CR) and partial response (PR), serving as a comprehensive measure of treatment efficacy in DLBCL.
Complete Response (CR) Rate: Of particular significance was the observation that 73.7% of patients achieved a complete response (CR) to Orelabrutinib-based therapy. Complete response, defined as the absence of detectable disease on imaging studies and normalization of clinical parameters, represents the optimal treatment outcome in DLBCL. The high CR rate observed in this study underscores the potential of Orelabrutinib to induce robust and durable responses in patients with DLBCL.
Partial Response (PR) Rate: In addition to complete responses, a subset of patients demonstrated partial responses (PR) to Orelabrutinib-based therapy, with a PR rate of 15.8%. Partial response indicates a significant reduction in tumor size or disease burden, albeit with residual disease remaining detectable on imaging studies. While not achieving the same level of disease control as complete response, partial response remains clinically meaningful and indicative of treatment efficacy.
Survival Outcomes: Survival outcomes, including overall survival (OS) and progression-free survival (PFS), were promising among patients treated with Orelabrutinib-based regimens. The estimated 2-year overall survival (OS) rate was 78.6%, indicating a favorable likelihood of survival for patients receiving Orelabrutinib therapy. Similarly, the estimated 2-year progression-free survival (PFS) rate was 72.2%, suggesting a significant period of disease control and freedom from disease progression following treatment initiation.
Adverse Events: Despite the efficacy observed, the analysis also identified notable adverse events associated with Orelabrutinib-based therapy. Common adverse events included neutropenia and anemia, which are consistent with expectations for targeted therapies in aggressive malignancies such as DLBCL. While these adverse events were manageable with supportive care measures, their occurrence highlights the importance of ongoing monitoring and proactive management of treatment-related toxicities.
Discussion:
The findings of this retrospective analysis shed light on the therapeutic potential of Orelabrutinib-based regimens in the management of Diffuse Large B-Cell Lymphoma (DLBCL). DLBCL represents a clinically heterogeneous group of lymphoid malignancies characterized by aggressive behavior and variable response to therapy. Traditional treatment approaches, including chemoimmunotherapy regimens such as R-CHOP, have been associated with significant toxicities and variable outcomes, particularly in patients with relapsed/refractory disease or those who are elderly or unfit for intensive chemotherapy. Consequently, there is an unmet need for novel therapeutic strategies that can improve efficacy while minimizing treatment-related adverse events.
Orelabrutinib, a potent and selective Bruton’s tyrosine kinase (BTK) inhibitor, has shown promising preclinical and clinical activity in various B-cell malignancies, including DLBCL. BTK plays a crucial role in B-cell receptor signaling, proliferation, and survival, making it an attractive therapeutic target in B-cell lymphomas. The rationale behind utilizing Orelabrutinib in DLBCL lies in its ability to disrupt B-cell signaling pathways, leading to apoptosis and inhibition of tumor growth.
The retrospective analysis presented here demonstrates encouraging results regarding the efficacy of Orelabrutinib-based regimens in DLBCL treatment. The high overall response rate (ORR) of 89.5% and the substantial proportion of patients achieving complete response (CR) highlight the potential of Orelabrutinib to induce meaningful clinical responses in this patient population. Furthermore, the favorable survival outcomes, with estimated 2-year overall survival (OS) and progression-free survival (PFS) rates of 78.6% and 72.2%, respectively, underscore the clinical benefit associated with Orelabrutinib therapy.
Importantly, the study also provides insights into the safety profile of Orelabrutinib-based regimens. While the observed adverse events, including neutropenia and anemia, are consistent with those reported for targeted therapies in aggressive malignancies, they were generally manageable and did not compromise the overall efficacy of treatment. Nonetheless, ongoing monitoring and optimization of supportive care strategies are essential to mitigate treatment-related toxicities and ensure the long-term safety of Orelabrutinib therapy.
Conclusion:
The retrospective analysis presented here offers valuable insights into the efficacy and safety of Orelabrutinib-based regimens in the management of Diffuse Large B-Cell Lymphoma (DLBCL). By evaluating treatment response, survival outcomes, and adverse events among patients treated with Orelabrutinib, this study contributes to the growing body of evidence supporting its potential as a therapeutic option in DLBCL.
The findings indicate that Orelabrutinib-based therapy is associated with a high overall response rate, with a significant proportion of patients achieving complete responses. Moreover, favorable survival outcomes, as evidenced by the estimated 2-year overall survival and progression-free survival rates, underscore the clinical benefit associated with Orelabrutinib treatment. Despite the occurrence of manageable adverse events, the efficacy observed suggests that Orelabrutinib holds promise as an effective and tolerable treatment option for patients with DLBCL.
These results have important implications for clinical practice, highlighting the potential role of Orelabrutinib in optimizing treatment outcomes and improving patient care in DLBCL. As a targeted therapy, Orelabrutinib offers the prospect of personalized treatment approaches tailored to individual patient characteristics and disease biology. Furthermore, its efficacy in patients with relapsed/refractory disease or those unsuitable for intensive chemotherapy underscores its versatility and applicability across different clinical scenarios.
The research article, titled “Efficacy and Safety of Orelabrutinib-Based Regimens in Diffuse Large B-Cell Lymphoma,” was co-authored by Ruowen Wei and Yingying Wu, who contributed equally and share first authorship. The corresponding author is Jun Fang, reachable via the provided email address. Affiliated with the Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology in Wuhan, China, the authors conducted this study. Published in “Clinical and Experimental Medicine,” the journal facilitates exchange between clinicians and researchers.
