Autologous vs allogeneic hematopoietic cell transplantation for the treatment of patients with PTCL-NOS or AITL who have failed first-line therapy

Patients with peripheral T-cell lymphoma (PTCL) that is either refractory or relapsed (R/R), have poor clinical outcomes. This includes PTCL subsets such as PTCL not otherwise specified (PTCL-NOS) and angioimmunoblastic T-cell lymphoma (AITL). For these patients, intensive salvage chemotherapy prior to either autologous hematopoietic cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) remains one of the limited treatment options. However, it remains uncertain which of these is the optimal treatment choice for those who are fit enough to undergo HSCT.

Here, we consider data from two studies exploring this challenging clinical question. Jun Du and colleagues published in JAMA Network Open, a systematic review of allo-HSCT vs auto-HSCT for patients with R/R PTCL.¹ In addition, exploring the question of whether allo-HSCT or auto-HSCT represents the best treatment choice in patients with PTCL-NOS and AITL, Kazuaki Kameda and colleagues² undertook a retrospective analysis of patients with T-cell lymphoma to examine how this treatment choice affected outcomes for these patients, results of which were presented at the 26th Congress of the European Hematology Association (EHA2021).

Study by Du et al.¹

Study design

Du and colleagues¹ conducted a systematic search on PubMed, Embase, the Cochrane Central Register of Controlled Trials, Wanfang, and the China National Knowledge Infrastructure database using the following terms:

• Refractory or relapsed peripheral T-cell lymphoma
• ASCT/autologous stem-cell transplantation
• Allo-HSCT/allogeneic stem-cell transplantation
• Therapeutic effect
• Treatment

Inclusion/exclusion criteria

Clinical trials and retrospective studies with more than 10 samples that were published between January 12, 2001, and October 1, 2020, were included. Patients in these studies had R/R PTCL with no age or sex restrictions and were treated with auto- or allo-HSCT. Studies that were included provided outcome measures such as complete response (CR), partial response (PR), overall survival (OS), progression-free survival (PFS), and transplantation-related mortality (TRM). Articles without OS, PFS, and TRM were excluded.

Outcome measures

The prespecified outcome measures were OS, PFS, and TRM.

Results

Of 6,548 records identified, 30 underwent data extraction. These selected studies included 880 patients who underwent allo-HSCT, and 885 who underwent auto-HSCT. Pooled results are reported in Table 1.

Table 1. OS, PFS, and TRM in patients receiving HSCT*

Allo-HSCT, allogeneic hematopoietic cell transplantation; auto-HSCT, autologous hematopoietic cell transplantation; OS, overall survival; PFS, progression-free survival; TRM, transplantation-related mortality. *Adapted from Du et al.1
Results % (95% CI)	Allo-HSCT patients (n = 880)	Auto-HSCT patients (n = 885)
3-year OS	50 (41−60)	55 (48−64)
3-year PFS	42 (35−51)	41 (33−51)
5-year OS	54 (47−62)	53 (44−64)
5-year PFS	48 (40−56)	40 (24−58)
3-year TRM	32 (27−37)	7 (2−23)

Discussion

The meta-analysis¹ supports that OS and PFS are similar in patients treated with either allo-HSCT or auto-HSCT, and that HSCT is an effective treatment for R/R PTCL. The results of the pooled analysis also suggest a higher TRM associated with allo-HSCT compared with auto-HSCT. While the study had strict enrollment criteria, it should be noted that most of the eligible studies were single-arm trials, and the data for some outcome measures were insufficient to perform a subgroup analysis.

Study by Kameda et al.²

Study design

The study by Kameda and colleagues² was a retrospective cohort analysis that identified patients from the Japan Society for Hematopoietic Cell Transplantation national database.

The study collected demographic, diagnostic, treatment, and clinical outcome data, including OS and PFS data.

Inclusion criteria

Inclusion criteria stated that all patients must have

• had a diagnosis of PTCL-NOS and AITL
• had HSCT (allo- or auto-) after two to four lines of prior therapy
• undergone allo- or auto-HSCT received between 2006 and 2018

Results

762 patients were identified:

• 449 with PTCL-NOS
• 313 with AITL

Chemosensitivity and remission status among the overall population were variable:

• Among the patients recruited, 494 were chemo-sensitive
  • 172 were in first CR
  • 112 were in first partial remission
  • 210 were relapsed sensitive
• The remaining 268 patients were chemo-refractory
  • 142 were primary refractory
  • 126 were relapsed refractory

Key differences between allo-HSCT and auto-HSCT patients, including demographic, clinical, and treatment considerations, can be seen in Table 2. Allo-HSCT were more likely to have a worse HSCT comorbidity index and worse performance status (both p < 0.001) than auto-HSCT patients.

Table 2. Demographics, treatment, and outcomes*

Allo-HSCT, allogeneic hematopoietic cell transplantation; auto-HSCT, autologous hematopoietic cell transplantation. *Adapted from Kameda et al.2
Parameter	Allo-HSCT patients	Auto-HSCT patients	p value
Median age, years	53	58	< 0.001
Received >2 lines of prior therapy, %	63	33	< 0.001
Median months to HSCT from diagnosis (range)	11 (2−214)	11 (2−154)	0.64
Median follow-up in months (range)	36 (1−150)	54 (3−160)	—

Outcome data

OS and PFS data were considered at 4 years survival and were calculated for each treatment response group, alongside 2-year nonrelapse mortality; these are represented in Table 3.

Table 3. OFS, PFS, and nonrelapse mortality data for patients treated with allo- or auto-HSCT*

Allo-HSCT, allogeneic hematopoietic cell transplantation; auto-HSCT, autologous hematopoietic cell transplantation; OS, overall survival; PFS, progression-free survival. *Adapted from Kameda et al.2
Outcome	Auto-HSCT	Allo-HSCT
4-year survival data, % (95%CI)
Chemo-sensitive OS	56 (49.9−61.1)	59.8 (50.8−67.9)
Chemo-sensitive PFS	43 (37.1−48.6)	54.2 (45.2−62.2)
Chemo-refractory OS	34.1 (23.5−44.9)	41.1 (33.4−48.7)
Chemo-refractory PFS	23.4 (14.9−33)	37.9 (30.2−45.2)
2-year nonrelapse mortality, % (95%CI)
Chemo-sensitive disease	9.7 (6.7−13.3)	23.3 (16.6−30.7)
Chemo-refractory disease	9.7 (4.7−16.8)	36.3 (29−43.7)

Multivariate analysis confirmed that treatment with allo-HSCT was a significantly better prognostic factor for PFS in chemo-sensitive patients (hazard ratio [HR], 0.68; 95% CI, 0.5−0.92; p = 0.01), but only marginally better for PFS in chemo-refractory patients (HR, 0.73; 95% CI, 0.52−1.01; p = 0.06). Further statistical analysis suggested a trend, without statistical significance, that allo-HSCT conferred better OS for relapsed-sensitive disease among chemo-sensitive patients (HR 0.61; 95% CI, 0.36−1.04; p = 0.07), and primary-refractory disease among chemotherapy refractory patients (HR 0.51; 95% CI, 0.29−0.89; p = 0.02).

Discussion

The results of the study² suggest that in patients with relapsed-sensitive or primary refractory PTCL-NOS or AITL, allo-HSCT may result in better outcomes for patients, including PFS and OFS. Given the higher morbidities associated with allo-HSCT compared to auto-HSCT, further work is needed to confirm these findings to inform future decisions about standard of care in this patient group.

Conclusion

Together, these studies suggest that for patients with R/R PTCL, both allo-HSCT and auto-HSCT are effective treatment choices. However, for certain subsets of R/R PTCL, allo-HSCT may result in increased survival, but with increased morbidities. Further work is needed to inform future clinical decision making for patients with R/R PTCL.