Editorial Note: The 2024 American Society of Hematology (ASH) Annual Meeting, held from December 7 to 10 in San Diego, remains the largest and most comprehensive international academic gathering in the field of hematology. Every year, it draws leading experts and scholars from across the globe for in-depth discussions and exchanges on groundbreaking research. This year, the lymphoma field witnessed several pivotal study outcomes. Oncology Frontier - Hematology Frontier invited Dr. Jun Shi from The Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, to provide a detailed analysis and commentary on two highly impactful studies presented during the meeting.

01: Lack of Benefit of Autologous Hematopoietic Cell Transplantation (auto-HCT) in Mantle Cell Lymphoma (MCL) Patients in First Complete Remission (CR) with Undetectable Minimal Residual Disease (uMRD): Initial Report from the ECOG-ACRIN EA4151 Phase 3 Randomized Trial (Abstract No: LBA-6)

Dr. Jun Shi：This study provides significant insights into the treatment of MCL, particularly as new therapies continue to emerge. A pressing clinical question has been whether these novel agents can replace auto-HCT. Encouragingly, this research challenges the traditional reliance on auto-HCT for patients in first CR with undetectable MRD, demonstrating that induction regimens—such as high-dose cytarabine, rituximab, and BTK inhibitors—can achieve deep remissions.

The study’s randomized design, involving 650 participants and rigorous stratification based on MIPI-c scores, enhances its methodological robustness and ensures reliable outcomes. The adoption of the highly sensitive clonoSEQ® MRD assay further strengthens patient stratification and the accuracy of outcome analysis. Subgroup analysis revealed that MRD+ patients might still benefit from auto-HCT, suggesting the potential for more personalized treatment strategies.

Study Limitations and Recommendations

1. Follow-Up Duration: A major limitation is the reliance on a median follow-up time of 2.7 years. While sufficient for assessing short-term outcomes, longer follow-up (over five years) is necessary to fully evaluate sustained survival and progression-free survival (PFS), as MCL treatment effects may evolve over time, especially with ongoing rituximab therapy.
2. Population Homogeneity: The study cohort was predominantly male (79%) and white (92%), which limits the generalizability of the findings to other racial and ethnic groups. Future studies should aim to include more diverse populations to ensure applicability across all MCL patients, regardless of gender or ethnicity.
3. Lack of Detailed Molecular Data: Although patients were stratified by MIPI-c scores, the absence of molecular markers (e.g., BTK mutations, TP53 status) reduces the ability to refine patient selection. Incorporating molecular data could help identify those most likely to benefit from auto-HCT or maintenance therapies, offering deeper insights into why some patients respond better than others to these treatments.

Final Thoughts

This study demonstrates that auto-HCT does not confer additional benefits in MCL patients who achieve deep remission. As novel therapies continue to evolve, they offer the promise of more cost-effective and less toxic alternatives for many patients. However, these findings require longer follow-up and further validation to solidify their implications for clinical practice.

02: Retreatment with R-CHOP-like Therapy in Patients with Late Relapse of Diffuse Large B-Cell Lymphoma (DLBCL)(Abstract No: 109)

Dr. Jun Shi：This study makes a significant contribution to the treatment of diffuse large B-cell lymphoma (DLBCL), especially by focusing on patients with late relapse (relapse occurring more than two years after diagnosis), who generally have better prognoses and retain sensitivity to the original regimen. This finding is particularly important for elderly patients or those with comorbidities who are unsuitable for high-intensity therapies, such as stem cell transplantation.

By utilizing real-world data from the BC Cancer Centre for Lymphoid Cancer Database, the study provides valuable clinical insights, bridging the gap between clinical trials and daily practice. The findings offer actionable information for clinicians. Subgroup analyses underscore the impact of relapse timing on treatment response, demonstrating significantly longer time to progression (TTP) for patients relapsing more than five years post-diagnosis. Furthermore, the study’s exploration of cell of origin (COO) and International Prognostic Index (IPI) provides essential context, enabling clinicians to tailor treatment more effectively.

The study highlights that R-CHOP-like therapy can deliver durable remissions with lower toxicity, making it particularly suitable for patients unable to tolerate intensive treatment regimens, thus preserving efficacy while improving quality of life.

Study Limitations and Recommendations

1. Retrospective Design: As a retrospective study, it inherently carries selection bias, with treatment decisions made based on clinical judgment rather than random assignment. Without a control group, the relative efficacy of R-CHOP-like therapy compared to other potential regimens or strategies cannot be definitively assessed.
2. Lack of Randomization: Although the study provides valuable data on retreatment outcomes, the absence of a randomized controlled trial (RCT) design necessitates cautious interpretation of the results. Randomization would eliminate bias and provide stronger evidence for the efficacy of R-CHOP-like therapy as a retreatment strategy.
3. Toxicity and Treatment Discontinuation: The fact that 36% of patients discontinued treatment due to toxicity or intolerance underscores the importance of addressing treatment-related adverse effects, particularly for elderly or comorbid patients. Future research should focus on identifying predictors of intolerance and developing methods to mitigate adverse effects in vulnerable populations.
4. Limited Follow-Up Duration: The study’s median follow-up of 29 months does not provide sufficient data on the durability of remission or long-term overall survival (OS). Longer follow-up is essential to determine whether the benefits of R-CHOP-like therapy persist over time, especially for older patients who may face long-term complications.

Final Thoughts

This study demonstrates that R-CHOP-like therapy can be an effective retreatment strategy for late-relapsed DLBCL patients, even those previously treated with R-CHOP. It holds particular promise for elderly or comorbid patients who cannot tolerate more aggressive therapies. However, the retrospective nature of the study limits the ability to draw definitive conclusions, underscoring the need for prospective trials to validate these findings.

About Dr. Jun Shi

Dr. Jun Shi is the Director of the Hematology Department at the Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine. A distinguished hematologist with a doctoral degree from Japan, Professor Shi is a chief physician and doctoral advisor. He serves as Vice President of the Shanghai Medical Association’s Internal Medicine and Hematology branches and as Deputy Chair of the Shanghai Association of Integrative Medicine’s Hematology Committee.

Professor Shi’s clinical expertise lies in the diagnosis and treatment of malignant lymphomas and hematopoietic stem cell transplantation. His primary research focuses on the tumor microenvironment in malignant hematologic diseases. He has led multiple national and provincial research projects, with articles published in prestigious journals such as Cancer Cell, Science Advances, and Haematologica.