In September 2023, a study led by Professor Jun Zhu from Peking University Cancer Hospital and Institute was published in the prestigious international academic journal ——Signal Transduction and Targeted Therapy (IF=38.12). The title of the study is "Long-term survival benefit of anti-PD-1 therapy in patients with relapsed or refractory classical Hodgkin lymphoma". This study evaluates PR and refractory disease have a negative impact on the survival beneit of anti-PD-1 therapeutics in patients with r/r cHL, which highlights the need for multimodal treatment strategies.
Hodgkin lymphoma represents a unique therapeutic challenge, particularly for those with relapsed or refractory disease after first-line therapies. Despite advances in treatment, the prognosis for this subgroup remains suboptimal. Anti-programmed cell death-1 (anti-PD-1) therapies have emerged as a promising treatment avenue, leveraging the body’s immune system to recognize and fight cancer cells. The efficacy and safety profile of these therapies in cHL have been encouraging in early-phase trials, but the long-term survival impact and optimal management strategies are not well understood. This study addresses these gaps by focusing on patients who have achieved an objective response to anti-PD-1 therapy, seeking to understand the factors influencing long-term outcomes.
This retrospective analysis consolidated data from four phase 2 clinical trials, each evaluating the efficacy of different anti-PD-1 therapies in treating relapsed or refractory cHL. The inclusion criteria were adults with confirmed cHL who had received at least one prior therapy and demonstrated an objective response to anti-PD-1 treatment. The analysis focused on progression-free survival (PFS) and overall survival (OS) as primary endpoints, employing Kaplan-Meier estimates for survival analysis. Additionally, the study explored the influence of various factors, including disease status at therapy initiation (refractory vs. non-refractory) and remission status post-treatment (complete remission vs. partial remission), on survival outcomes. Multivariate Cox regression models were used to adjust for potential confounders.
The study’s findings underscore the effectiveness of anti-PD-1 therapy in extending the lives of patients with relapsed or refractory cHL. Notably, the distinction in survival outcomes between patients achieving complete remission and those with partial remission highlights the importance of achieving a deep response to treatment. The analysis revealed that beyond remission status, factors such as the presence of B symptoms, the number of prior treatment lines, and the bulk of disease at the initiation of anti-PD-1 therapy were significant predictors of survival outcomes. These results suggest that the biological behavior of cHL and patient-specific factors play critical roles in determining the long-term benefit of anti-PD-1 therapy.
(Signal Transduct Target Ther,2023 Sep 20;8(1):356. doi: 10.1038/s41392-023-01600-7.)
Achieving complete remission with anti-PD-1 therapy significantly enhances long-term survival for patients with relapsed or refractory cHL, underscoring the therapy’s value in this challenging clinical context. However, the study also identifies a subset of patients who, despite responding to treatment, have inferior outcomes, particularly those with partial remission or refractory disease at the outset. These findings emphasize the need for personalized treatment approaches and potentially the integration of anti-PD-1 therapy with other therapeutic modalities to maximize patient outcomes. The question of optimal treatment duration also emerges as a crucial area for future research, suggesting that extended therapy may benefit certain patients.
This comprehensive analysis contributes significantly to the understanding of anti-PD-1 therapy’s role in treating relapsed or refractory cHL. By highlighting the factors that influence long-term survival, the study informs clinical decision-making and underscores the necessity for a strategic approach to treatment, incorporating patient-specific considerations and potentially combining anti-PD-1 therapy with other treatment modalities. Furthermore, these findings pave the way for future research aimed at optimizing treatment strategies, including the exploration of biomarkers for response prediction and the development of novel combination therapies. Ultimately, this study reinforces the importance of personalized medicine in improving outcomes for patients facing relapsed or refractory cHL.
