Autologous stem-cell transplantation (ASCT) has emerged as a more effective treatment option compared to CAR T-cell therapy for patients with relapsed large B-cell lymphoma (LBCL) in complete remission, according to a retrospective analysis. The study, presented at the American Society of Hematology (ASH) meeting, demonstrated that ASCT was associated with significantly fewer relapses at 2 years and improved progression-free survival (PFS) and overall survival (OS) rates compared to CAR T-cell therapy. These findings offer valuable insights into the treatment landscape for LBCL and emphasize the importance of considering ASCT as a viable therapeutic option.
The analysis revealed that patients who underwent ASCT had a lower relapse rate at 2 years, indicating a more sustained response to treatment. Additionally, ASCT demonstrated superior PFS and OS rates compared to CAR T-cell therapy. These results underscore the effectiveness of ASCT as a potentially curative therapy for patients with relapsed LBCL. The study’s lead author, Dr. Mazyar Shadman, emphasized that these findings confirm the current standard of care, which involves salvage therapy with autotransplant for patients who relapse after first-line treatment.
In the subgroup of patients experiencing early treatment failure, ASCT was particularly beneficial. This subset of patients had a significantly lower 2-year relapse rate when treated with ASCT compared to CAR T-cell therapy. This suggests that ASCT should be considered as an early intervention for patients who have not responded well to initial therapy. By using ASCT in these cases, clinicians can provide another potentially curative treatment option while still having CAR T-cell therapy available as a backup plan in the later stages of therapy.
It is important to note that the study focused on patients who were in complete remission after initial relapse. For these patients, the choice between CAR T-cell therapy and ASCT becomes critical. While CAR T-cell therapy has become the standard of care for relapsed LBCL, it is essential to consider individual patient characteristics and response to previous treatments. Shadman proposed that if patients achieve a good clinical response and are considered suitable for autotransplant, ASCT could be a reasonable option to discuss. This personalized approach to treatment decision-making takes into account the potential benefits and limitations of each therapeutic strategy.
During the discussion following the presentation, concerns were raised regarding the potential risk of secondary malignancies associated with CAR T-cell therapy, as highlighted by a recent safety communication from the FDA. However, Shadman acknowledged that the number of CAR T-cell-related malignancies remains extremely low compared to the overall benefit of CAR T-cell therapy in curing a significant percentage of patients with limited treatment options. He maintained that these safety concerns should be followed closely, but they should not deter clinicians from offering curative therapy for relapsed lymphoma.
The study found no significant difference in treatment-related mortality between ASCT and CAR T-cell therapy. This suggests that both treatment approaches have similar safety profiles and should be considered based on their respective efficacy outcomes. Shadman also highlighted that high-dose chemotherapy, often used alongside ASCT, also carries a risk of secondary malignancies. Therefore, it is crucial to carefully evaluate the potential risks and benefits of each treatment option and tailor the approach to the individual patient’s needs.
While the retrospective analysis provided valuable insights into the comparative effectiveness of ASCT and CAR T-cell therapy, Shadman acknowledged several limitations. These include potential confounders that could not be eliminated, the necessity for randomized trials to directly compare the two treatment approaches in patients with LBCL in complete remission, and the predominant use of tisagenlecleucel (Kymriah), which may have resulted in an underestimation of the efficacy of CAR T-cell therapy. Further research is warranted to fully understand the optimal sequencing and integration of these treatment modalities in the management of relapsed LBCL.
The retrospective analysis provides compelling evidence for the superiority of ASCT over CAR T-cell therapy in patients with relapsed LBCL in complete remission. ASCT demonstrated lower relapse rates, improved PFS and OS rates, and comparable treatment-related mortality. These findings support the use of ASCT as a potentially curative therapy for relapsed LBCL patients. However, treatment decisions should be individualized, taking into account each patient’s specific characteristics and response to prior therapies. Further research is necessary to refine treatment strategies and optimize outcomes for this patient population. Ultimately, the goal remains the same: to provide personalized, effective, and curative therapies for patients with relapsed LBCL.