Impact of Reduced-Intensity Conditioning Regimens on Outcomes in Diffuse Large B Cell Lymphoma Undergoing Allogeneic Transplantation

Epperla, Narendranath; Ahn, Kwang Woo; Khanal, Manoj; Litovich, Carlos; Ahmed, Sairah; Ghosh, Nilanjan; Fenske, Timothy S.; Kharfan‐Dabaja, Mohamed A.; Sureda, Anna; Hamadani, Mehdi

doi:10.1016/j.bbmt.2020.09.014

Cited by 24 publications

(21 citation statements)

References 29 publications

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“…The allo‐HCT conditioning regimens have a spectrum of dose‐intensities, ranging from regimens at the lower end of the intensity spectrum (relying predominately on immunological effects to eradicate disease) to higher‐intensity options (depending on both cytoreductive and immunological mechanisms to control disease) 11 . Reduced‐intensity and non‐myeloablative conditioning (RIC/NMA) regimens now account for the vast majority of allo‐HCTs performed for lymphomas in the United States 7,11–16 . Although the RIC regimens are generally associated with a lower cumulative incidence of non‐relapse mortality (NRM) relative to myeloablative conditioning (MAC) regimens, disease relapse remains the most common cause of treatment failure in patients with lymphoma undergoing allo‐HCT.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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“…40 Because, in such patients, higher-intensity conditioning regimens are associated with higher NRM and inferior OS, 40 it is important to use lower-intensity conditioning platforms to minimize the risk of procedure-related morbidity and mortality. 20,33,34,39 In conclusion, this noncomparative, retrospective, registry analysis shows that both CAR-T and alloHCT can provide durable remissions in a subset of patients with DLBCL relapsing after prior autoHCT. The profiles of patients benefiting from these approaches are distinct.…”

Section: Discussionmentioning

confidence: 66%

“…We acknowledge that additional variables (eg, metabolic tumor volumes, CAR-T cell fitness, composition and expansion, bilirubin level, lactate dehydrogenase, Eastern Cooperative Oncology Group performance score) 32,36,37 18 This difference is possibly because of general improvements in HCT supportive care, advances in GVHD prevention and treatment, 38 and the restriction of the current cohort to RIC regimens. 18,33,39 The CIBMTR prognostic score of high/very high-risk disease identifies a cohort of patients at particularly high risk of therapy failure after both CAR-T therapy or alloHCT. Effective approaches to mitigate risk of therapy failure after alloHCT or CAR-T treatment of such patients is clearly an area of unmet need, and investigation of novel maintenance or consolidation approaches in this setting are warranted.…”

Section: Discussionmentioning

confidence: 99%

Allogeneic transplant and CAR-T therapy after autologous transplant failure in DLBCL: a noncomparative cohort analysis

et al. 2022

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Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR) T-cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto) HCT. While the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis we report outcomes of DLBCL patients (≥18 years), undergoing a reduced intensity alloHCT or CAR-T therapy during 2012-2019, after a prior auto-HCT failure, and apply CIBMTR prognostic model to CAR-T recipients. 584 patients were included. The 1-year relapse, non-relapse mortality, overall survival (OS) and progression-free survival (PFS) for CAR-T treatment after autoHCT failure were were 39.5%, 4.8%, 73.4% and 55.7%, respectively. The corresponding rates in alloHCT cohort were 26.2%, 20.0%, 65.6% and 53.8%, respectively. The 1-year OS of alloHCT recipients classified as low-, intermediate- and high/very high-risk groups according to the CIBMTR prognostic score was 73.3%, 59.9%, and 46.3, respectively (p=0.002). The corresponding rates for low-, intermediate- and high/very high-risk CAR-T patients were 88.4%, 76.4%, and 52.8%, respectively (p<0.001). This registry analysis shows that both CAR-T and alloHCT can provide durable remissions in subset of DLBCL patients relapsing after a prior autoHCT. The simple, CIBMTR prognostic score can be used to identify patients at high risk of treatment failure after either procedure. Evaluation of novel relapse mitigations strategies after cellular immunotherapies are warranted in these high risk patients.

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“…Most allo‐HCT in NHL are performed with RIC/non‐myeloablative (NMA) conditioning, which has allowed its use in patients who are otherwise not eligible for a myeloablative conditioning (MAC) regimen. In fact, recent registry‐based studies have shown high NRM and poor survival outcomes with higher intensity RIC regiments such as fludarabine/melphalan compared to fludarabine/busulfan 74,75 . As shown in Table II, post‐CAR T allo‐HCT was infrequently used in published CAR T studies, most of which did not include patients with previous history of allo‐HCT.…”

Section: Lymphomamentioning

confidence: 99%

“…The choice of conditioning regimen, stem cell graft source, and donor type for allo‐HCT should follow usual institutional protocols. In NHL, we suggest using lower intensity RIC regimens to lower the risk of NRM in heavily pre‐treated patients 75 . In patients with history of allo‐HCT before CAR T, whether to use the same or a different donor for second allo‐HCT is not clear.…”

Section: Allo‐hct After Car T Therapy: Practical Issuesmentioning

confidence: 99%

The evolving role of allogeneic haematopoietic cell transplantation in the era of chimaeric antigen receptor T‐cell therapy

et al. 2021

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Summary Chimaeric antigen receptor T‐cell (CAR T) therapy has revolutionized the management of many haematological malignancies. It is associated with impressive disease responses in relapsed or refractory high‐grade B‐cell non‐Hodgkin lymphoma (B‐NHL) and acute lymphoblastic leukaemia (B‐ALL) with durable remissions in a subset of patients. Historically, haematopoietic cell transplantation (HCT) has been the standard consolidation strategy for many of these patients who are now being treated with CAR T. Relapses are frequent after CD19 CAR T therapy in B‐ALL and consolidation with allogeneic HCT (allo‐HCT) may improve survival of patients with high‐risk disease. There appears to be a clear difference in B‐ALL outcomes between paediatric and adult patients, with the latter having a much higher risk of relapse after CAR T therapy. Late relapses are infrequent in patients with B‐NHL and consolidation with allo‐HCT may not be needed in patients who achieve a complete remission after CAR T therapy. Future registry‐based and prospective studies will hopefully provide the needed data in the future to risk‐stratify the recipients of CAR T therapy. Meanwhile, we provide guidance on patient selection and practical issues with performing allo‐HCT after CAR T therapy.

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Impact of Reduced-Intensity Conditioning Regimens on Outcomes in Diffuse Large B Cell Lymphoma Undergoing Allogeneic Transplantation

Cited by 24 publications

References 29 publications

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

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

Allogeneic transplant and CAR-T therapy after autologous transplant failure in DLBCL: a noncomparative cohort analysis

The evolving role of allogeneic haematopoietic cell transplantation in the era of chimaeric antigen receptor T‐cell therapy

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