Continued risk of relapse in peripheral T-cell lymphoma even in patients who achieved complete response after initial therapy

Abstract Background: Peripheral T-cell lymphomas (PTCLs) are a rare subtype of aggressive lymphomas. Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) has been the standard initial therapy for PTCL; however, clinical outcomes remain suboptimal. The introduction of brentuximab vedotin (BV)-CHP has improved survival in CD30-positive PTCL patients (pts) and has become the standard therapy for this subgroup. While several novel agents have been introduced for relapsed/refractory settings, their impact on survival outcomes remains unclear. Additionally, early relapse within 12 or 24 months of initial therapy is known to predict poor prognosis. However, few studies have specifically focused on outcomes and prognostic factors in pts who relapsed after achieving complete response (CR). Therefore, we evaluated clinical outcomes of PTCL pts, with a particular focus on those who achieved CR after initial therapy. Methods: We retrospectively analyzed consecutive pts with PTCL who received initial therapy without up-front autologous stem cell transplantation at our institution between 2005 and 2024. Results: A total of 102 pts were analyzed, with the median age of 62 years (range: 16-83). Sixty-five pts were male and 37 were female. Forty-eight pts had PTCL-NOS, 33 had nodal T-follicular helper cell lymphoma, 10 had ALK-negative ALCL, 8 had ALK-positive ALCL, one had breast implant-associated ALCL, and the remaining two pts had an undetermined subtype. Seventy-one pts (69%) had advanced-stage disease. One hundred pts (98%) received CHOP or CHOP-like regimens, including 17 who received BV-CHP. The overall response rate (ORR) was 78% (81/102), and the CR rate was 58% (59/102). The median follow-up duration among surviving pts was 43.5 months (range, 5–188). The median progression-free survival (PFS) was 14 months (95% CI, 8-27), and the median overall survival (OS) was 68 months (95% CI, 37-110). Pts who achieved CR had a significantly longer median PFS (45 months; 95% CI, 21–78) than those who did not (5 months; 95% CI, 3–6; HR, 0.25; 95% CI, 0.16–0.40). The median OS was also significantly longer in pts who achieved CR (110 months [95% CI, 57–154] vs. 20 months [95% CI, 12–47]; HR, 0.32; 95% CI, 0.18–0.57) than those who did not. In multivariate analysis, inferior PFS was associated with subtypes other than ALK-positive ALCL (HR, 11.15; 95% CI, 1.52-81.68), bone marrow involvement (HR, 3.07; 95% CI, 1.41-6.70), and failure to achieve CR with the initial therapy (HR, 3.77; 95% CI, 2.27-6.26). For OS, the only independent adverse prognostic factor was failure to achieve CR (HR, 2.39; 95% CI, 1.29-4.42). Based on these findings, we subsequently analyzed the 59 pts who achieved CR after initial therapy. Thirty-five of 59 pts (59%) experienced relapse, with the 2- and 5-year cumulative relapse rates of 38% and 52%, respectively, and a median time to relapse of 46 months (95% CI, 21-115). Of the 33 pts who subsequently received salvage therapy, 22 received at least one novel agent (e.g., BV, romidepsin, pralatrexate, tucidinostat), and 19 received conventional chemotherapy. A landmark analysis from the time of first relapse showed a median PFS of 9 months (95% CI, 3-17), and a median OS of 29 months (95% CI, 17-42). No significant differences in PFS and OS were observed based on the duration of initial response: The median PFS was 10 months for pts who relapse within 12 months, 9 months for those who relapse between 13-24 months, and 9 months for those who relapse after 24 months (HR, 1.02; 95% CI, 0.67-1.56). The median OS was 28 months, 47 months, 42 months, respectively (HR, 0.81; 95% CI, 0.48-1.36). Conclusion: PTCL pts who achieved CR after initial therapy demonstrated favorable long-term survival. However, more than half experienced relapse, with no clear plateau in relapse risk. This finding indicates a continued risk of relapse and highlights the need for long-term monitoring. Among these pts, the duration of initial response did not significantly impact post-relapse survival. Despite the availability of novel agents, PFS after relapses remained poor, underscoring the need for improved treatment strategies, such as post-remission consolidation therapy, to prevent relapse and further improve long-term outcomes in pts with PTCL.