Impact of conditioning regimen intensity on the outcomes of peripheral T‐cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T‐cell lymphoma patients undergoing allogeneic transplant

Abstract

Summary There have been no large studies comparing reduced‐intensity/non‐myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T‐cell non‐Hodgkin lymphoma (T‐NHL) patients undergoing allogeneic transplant (allo‐HCT). A total of 803 adults with peripheral T‐cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T‐cell lymphoma (age 18–65 years), undergoing allo‐HCT between 2008–2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation‐specific comorbidity index (HCT‐CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79–1.29; p = 0.95). Similarly, non‐relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61–1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98–1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92–1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3–4 acute graft‐versus‐host disease (HR = 0.67; 95% CI = 0.46–0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo‐HCT for T‐cell NHL.

Allogeneic haematopoietic cell transplant in patients with relapsed/refractory anaplastic large cell lymphoma

“…This is similar to a previous study in T‐cell NHL (not limited to ALCL) from the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM‐TC) of 285 patients who underwent allo‐HCT for PTCL 36 . In addition, Savani et al 13 reported similar findings in a recently published CIBMTR analysis. The 5‐year OS, PFS and NRM were not different in the patients who received RIC/NMA versus those who received MAC, while the risk of Grade 2–4 GVHD was higher in the MAC cohort.…”

“…12 Adoptive immunotherapy in the form of allogeneic HCT (allo-HCT) is a potentially curative treatment for patients with select R/R T-cell lymphomas. [13][14][15] In fact, with the recent decreased utilisation of allo-HCT in diffuse large B-cell lymphoma, T-cell NHL has now become the most common indication of allografting for lymphomas in the United States. [14][15][16] However, the role of allo-HCT in R/R ALCL is not well defined.…”

Fludarabine plus reduced-intensity busulfan versus fludarabine plus myeloablative busulfan in patients with non-Hodgkin lymphoma undergoing allogeneic hematopoietic cell transplantation

“…Developing chimeric antigen receptor T cell therapy has remarkably changed the landscape of relapsed and refractory lymphoma, especially diffuse large B cell lymphoma; however, approximately 60% of patients ultimately experience relapse, and the median PFS was only 5.9 months in the ZUMA-1 trial, which confirmed the efficacy of axicabtagene ciloleucel in patients with relapsed and refractory large B cell lymphoma [ 38 – 40 ]. Allogeneic HCT continues to play an important role in patient management; therefore, further developments are needed to improve outcomes, and the results of allogeneic HCT in patients with NHL in this study and previous studies are inadequate [ 14 , 18 , 29 , 31 – 34 ]. As suggested in our study, it may be useless to rely on simply increasing conditioning of patients with NHL.…”

“…On the other hand, several retrospective studies of patients with myelodysplastic syndromes reported no statistically significant differences in relapse and OS between RIC and MAC [ 12 , 13 ]. Regarding patients with NHL, RIC has a similar or higher OS compared with that of MAC [ 14 , 18 , 29 , 31 – 34 ]; however, only a few studies have compared the effects of simple antitumor drug volumes with Flu/Bu2 and Flu/Bu4. The largest retrospective study from the European Society for Blood and Marrow Transplantation compared Flu/Bu2 and fludarabine plus a myeloablative dose of busulfan (Flu/Bu3/4) in patients from a cohort consisting of approximately 90% chemosensitive NHL patients [ 14 ].…”

Allogeneic Blood or Marrow Transplantation with Post-transplantation Cyclophosphamide for Peripheral T-cell Lymphoma: Importance of Graft Source

“…39 PB allografts have also been associated with reduced risk of relapse and improved survival in patients with Hodgkin lymphoma who underwent alloBMT with RIC. 40 While some studies have found no association between graft source and survival outcomes in PTCL, 28 source may be in uenced by conditioning regimen, 41 donor selection, 28 and histology/disease characteristics. 26 In our study, all patients received NMA conditioning with PTCy, regardless of histology or other clinical features.…”