Abstract: Refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) poses significant therapeutic challenges, particularly in cases where chimeric antigen receptor T-cell (CAR-T) therapy fails. This retrospective study aimed to evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) as a salvage option for R/R DLBCL patients following CAR-T therapy failure. Data were analyzed from 10 patients who relapsed after CAR-T therapy between October 2017 and June 2022. Post-CAR-T failure treatments included various regimens, and therapeutic responses were assessed using the Lugano 2014 criteria. Following allo-HSCT, the majority of patients achieved complete or partial remission, resulting in an objective response rate of 60%. The 1-year overall survival and progression-free survival rates were 70% and 40%, respectively. However, non-relapse mortality was notable at 20%, primarily due to transplant-related complications. This study provides evidence supporting allo-HSCT as a salvage treatment for R/R DLBCL patients following CAR-T therapy failure, emphasizing the importance of careful patient selection and proactive management of transplant-related risks. Further research is warranted to optimize treatment strategies and refine patient selection criteria in this challenging clinical scenario.Introduction:
Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment landscape for refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL). However, despite its remarkable efficacy, a subset of patients experiences treatment failure, presenting significant therapeutic challenges. In such cases, alternative strategies are urgently needed to improve outcomes and prolong survival. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has emerged as a potential salvage option for these patients. This retrospective study aims to evaluate the efficacy and safety of allo-HSCT in R/R DLBCL patients following CAR-T therapy failure.
Study Design and Methods:
The retrospective single-center study conducted at the First Affiliated Hospital of Soochow University focused on R/R DLBCL patients who relapsed after CAR-T therapy between October 2017 and June 2022. This period was chosen to ensure a sufficient sample size while capturing recent developments in CAR-T therapy and allo-HSCT. Patient data were meticulously collected and analyzed, adhering to rigorous criteria for inclusion and evaluation.
The therapeutic effect evaluation was based on the Lugano 2014 criteria, a widely recognized standard for assessing lymphoma response. This ensured consistency and reliability in evaluating treatment outcomes across patients. Post-CAR-T failure treatments varied, reflecting the complexity of managing relapsed/refractory disease. Venetoclax-based and ibrutinib+tislelizumab therapies were among the regimens utilized, with some patients not receiving any intermediate therapy, highlighting the diversity of approaches in clinical practice.
Detailed patient characteristics, including age, sex distribution, and disease stage at the time of allo-HSCT, were thoroughly documented. This allowed for a comprehensive understanding of the patient population under study. The inclusion of patients at an advanced disease stage (80% at stage IV) underscores the critical need for effective salvage therapies in this high-risk population.
Results:
The analysis encompassed data from 10 R/R DLBCL patients, providing valuable insights into the efficacy of allo-HSCT following CAR-T therapy failure. Despite the small sample size, the study yielded clinically relevant findings with implications for patient management and treatment decision-making.
Patient demographics revealed a median age of 43.5 years and an equal distribution of sexes, indicating a representative sample reflective of the broader R/R DLBCL population. Notably, the best responses to CAR-T therapy varied, with 30% achieving complete remission (CR), 40% partial remission (PR), and 30% exhibiting stable disease/progressive disease (SD/PD). This diversity in response underscores the heterogeneity of DLBCL and the challenges in achieving durable remissions.
Following allo-HSCT, the majority of patients (50%) achieved CR, while one patient attained PR, resulting in an objective response rate (ORR) of 60%. These findings suggest the potential efficacy of allo-HSCT in inducing meaningful responses in a subset of R/R DLBCL patients after CAR-T therapy failure. The observed 1-year overall survival (OS) and progression-free survival (PFS) rates of 70% and 40%, respectively, highlight the potential of allo-HSCT to prolong survival in this challenging clinical scenario.
However, the study also revealed significant non-relapse mortality (NRM) of 20.0%, primarily attributed to acute renal failure and severe pulmonary infection. While allo-HSCT offers therapeutic promise, the associated risks underscore the importance of careful patient selection and proactive management of transplant-related complications.
Discussion:
The findings of this study shed light on the role of allo-HSCT as a salvage option for R/R DLBCL patients following CAR-T therapy failure. Despite the established efficacy of CAR-T therapy in this setting, a subset of patients experience treatment refractoriness or relapse, necessitating alternative therapeutic strategies. Allo-HSCT emerges as a promising approach, offering the potential for durable remissions and improved survival outcomes.
The observed ORR, OS, and PFS rates following allo-HSCT underscore its therapeutic utility in selected patients. However, the relatively high NRM rate highlights the need for cautious consideration of transplant-related risks and careful patient selection. Individualized evaluation post-CAR-T therapy is essential to identify suitable candidates for allo-HSCT, taking into account factors such as disease biology, comorbidities, and transplant eligibility criteria.
Overall, this study contributes valuable insights into the evolving treatment landscape of R/R DLBCL and highlights the need for further research to optimize patient selection criteria and refine treatment algorithms in the era of novel therapies such as CAR-T and allo-HSCT. By leveraging emerging evidence and adopting a tailored approach to patient care, clinicians can maximize therapeutic outcomes and improve the prognosis of this challenging patient population.
Conclusion: This retrospective study underscores the potential of allogeneic hematopoietic stem cell transplantation (allo-HSCT) as a salvage treatment for refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) patients following chimeric antigen receptor T-cell (CAR-T) therapy failure. Despite the inherent challenges and associated risks, allo-HSCT demonstrated promising efficacy in inducing meaningful responses and prolonging survival outcomes in a subset of patients.
The observed objective response rate, 1-year overall survival, and progression-free survival rates following allo-HSCT highlight its therapeutic utility in selected R/R DLBCL patients post-CAR-T failure. However, the significant non-relapse mortality underscores the importance of careful patient selection and proactive management of transplant-related complications.
Moving forward, further research is warranted to optimize treatment algorithms, refine patient selection criteria, and mitigate transplant-related risks in this complex clinical scenario. By leveraging emerging evidence and adopting a tailored approach to patient care, clinicians can maximize therapeutic outcomes and improve the prognosis of R/R DLBCL patients who fail to respond to CAR-T therapy.
Leadership and Collaboration:
The pivotal study on allogeneic hematopoietic stem cell transplantation (allo-HSCT) outcomes in refractory/relapsed diffuse large B-cell lymphoma (R/R DLBCL) post CAR-T therapy failure was spearheaded by Dr. Haiwen Huang (HH) from the National Clinical Research Center for Hematologic Diseases at the First Affiliated Hospital of Soochow University, Suzhou, China. Dr. Huang, serving as the first and corresponding author, played a central role in the study’s conception, design, execution, and manuscript preparation. Collaborating closely with Dr. Huang were Mengya Cong (MC) and Sicheng Ai (SA), along with a dedicated team of researchers, who contributed significantly to various aspects of the study, including data analysis and manuscript drafting.
Moreover, Dr. Huang, along with Depei Wu (DW), assumed critical roles in revising the manuscript and providing final approval for its submission, highlighting their commitment to the integrity and accuracy of the research findings. As the point of contact for further inquiries regarding the study, Dr. Huang’s leadership underscores the collaborative efforts of both academic and clinical experts involved in this endeavor.
