Peripheral T-cell lymphomas (PTCLs) present clinicians with a series of complex challenges. PTCLs are a rare but highly clinically heterogenous group of non-Hodgkin lymphomas for which optimal therapy has not been fully defined.1 These diagnoses have a high risk of treatment failure and poor outcomes following relapse or the development of therapeutic refractoriness. While clinical trials have helped to create greater clinical clarity for B-cell lymphomas, the profound clinical variability of PTCLs and limited patient risk stratification have led to modest improvements in clinical outcomes for this population.2
Both autologous hematopoietic stem cell transplantation (HSCT) and allogeneic HSCT may play a role in the treatment of select patients with PTCL. Both modalities are included in current treatment guidelines as potential therapeutic consolidation strategies for high-risk patients or those with relapsed, refractory, or persistent PTCL. The challenges lie in effectively applying either autologous HSCT or allogeneic HSCT to the appropriate subset of patients. Because toxic effects, risks, transplantation-related mortality (TRM) rates, and potential effectiveness for these transplantation approaches differ so substantially, the clinical evidence that would allow for a more consistent selection of optimal therapy is lacking. There are no randomized trials that can empower selection between either modality for a particular patient.
In their review of the literature and meta-analysis comparing autologous HSCT and allogeneic HSCT for patients with PTCL, Du and colleagues3 have taken on an enormously ambitious task. The authors have chosen to try to better define the most appropriate role for these treatment modalities. The authors identified 6548 internationally published articles before focusing on a core of 30 articles that met their stringent inclusion criteria. This core set included data for 1765 patients undergoing transplantation, 880 treated with allogeneic HSCT and 885 treated with autologous HSCT. The authors were able to calculate overall survival (OS), progression-free survival (PFS), and TRM rates for patients receiving either type of transplantation. They found that the 3-year OS and PFS rates for autologous HSCT were 55% (95% CI, 48%-64%) and 41% (95% CI, 33%-51%), respectively. The 3-year OS and PFS rates for allogeneic HSCT were 50% (95% CI, 41%-60%) and 42% (95% CI, 35%-51%), respectively. The most striking outcome difference between the 2 transplantation modalities was in the risk of 3-year TRM, 7% (95% CI, 2%-23%) and 32% (95% CI, 27%-37%) for autologous HSCT and allogeneic HSCT, respectively. The authors noted that much of the long-term additional risk of allogeneic HSCT was primarily associated with the development of graft-vs-host disease (GVHD) in that population.
In reviewing the literature related to patient outcomes for autologous HSCT and allogeneic HSCT for patients with PTCL, Du and colleagues3 have achieved a significant accomplishment, and these data add to our knowledge regarding the association of these transplantation modalities with outcomes in this patient population. However, this article also illustrates the significant limitations that constrain interpretation of the data gleaned from such an ambitious meta-analysis. This meta-analysis shows how the complexities of data harmonization from a diverse array of clinical trials may produce a parallax view with some statistical hiccups, including a 5-year OS that appears to exceed the 3-year OS. However, at a deeper level, it serves to illustrate the need for caution in interpreting data gleaned from such an analysis.
Given the marked diversity of histological subtypes (and resulting clinical risk) within the domain of PTCL, it is essential to recall that these are all not clinically superimposable patient populations. Conclusions reached through the comingling of a series of complex patient subpopulations should be interpreted with great caution. It is also important to note that key clinical factors, such as prior treatment, comorbidities, fitness, and responsiveness to prior treatment all factor into the decision to pursue either autologous HSCT or allogeneic HSCT for a particular patient; the connectedness between such key factors and patient outcomes is not adequately captured in such a broad meta-analytical approach.
It is also essential to recall that autologous HSCT is more commonly used as part of a consolidation strategy for patients in remission, while allogeneic HSCT is more frequently used for patients with relapsed, persistent, or refractory PTCL. There are no insights that are generalizable from this study that would lead clinicians to alter their current patient selection paradigms or to clearly demonstrate which approach is globally preferable.
The data from this meta-analysis provide evidence that for select patients with PTCL, both autologous HSCT and allogeneic HSCT may be a potentially effective approach to treatment. This meta-analysis falls short of providing a rigorous, risk-segmented analysis of which modality is more likely to be most effective for a particular patient. As such, it does not provide a Rosetta Stone for unlocking the secrets of how best to manage this complex, highly clinically diverse set of patients. Despite the incremental insights achieved through this analysis, there is still far to go in identifying the optimal approach for an individual patient with PTCL.
Published: May 27, 2021. doi:10.1001/jamanetworkopen.2021.11674
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Alvarnas JC et al. JAMA Network Open.
Corresponding Author: Joseph C. Alvarnas, MD, City of Hope National Medical Center, 1500 E Duarte Rd, Duarte, CA 91010 (email@example.com).
Conflict of Interest Disclosures: Dr Zain reported serving as a consultant for Seagen, Secura Bio, and Verastem Oncology outside the submitted work. No other disclosures were reported.
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Alvarnas JC, Vanderplas A, Zain J. Autologous vs Allogeneic Hematopoietic Cell Transplantation for Patients With Peripheral T-cell Lymphomas—Closer, Yet Still So Far to Go. JAMA Netw Open. 2021;4(5):e2111674. doi:10.1001/jamanetworkopen.2021.11674
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