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Is autologous transplant in relapsed DLBCL patients achieving only a PET+ PR appropriate in the CAR T-cell era?

ABSTRACT: For relapsed chemosensitive diffuse large B-cell lymphoma (DLBCL), consolidation with autologous hematopoietic cell transplantation (auto-HCT) is a standard option. With the approval of anti-CD19 chimeric antigen receptor T cells in 2017, the Center for International Blood and Marrow Transplant Research (CIBMTR) reported a 45% decrease in the number of auto-HCTs for DLBCL in the United States. Using the CIBMTR database, we identified 249 relapsed DLBCL patients undergoing auto-HCT from 2003 to 2013 with a positive positron emission tomography/computed tomography (PET/CT)+ partial response prior to transplant were identified. The study cohort was divided into 2 groups: early chemoimmunotherapy failure (ECF), defined as patients with primary refractory disease (PRefD) or relapse within 12 months of diagnosis and late chemoimmunotherapy failure, defined as patients relapsing after ≥12 months. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS) and relapse. A total of 182 patients had ECF, whereas 67 did not. Among ECF cohort, 79% had PRefD. The adjusted 5-year probabilities for PFS and OS (ECF vs no ECF) were not different: 41% vs 41% (P = .93) and 51% vs 63% (P = .09), respectively. On multivariate analysis, ECF patients had an increased risk for death (hazard ratio, 1.61; 95% confidence interval, 1.05-2.46; P = .03) but not for PFS or relapse. In conclusion, for relapsed chemosensitive DLBCL patients with residual PET/CT+ disease prior to auto-HCT, the adjusted 5-year PFS (41%) was comparable, irrespective of time to relapse. These data support ongoing application of auto-HCT in chemosensitive DLBCL.

SUBMITTER: Shah NN

PROVIDER: S-EPMC7955408 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:In patients with relapsed DLBCL in complete remission (CR), autologous hematopoietic cell transplantation (auto-HCT) and CAR-T therapy are both effective, but it is unknown which modality provides superior outcomes. We compared the efficacy of auto-HCT vs. CAR-T in patients with DLBCL in a CR. A retrospective observational study comparing auto-HCT (2015-2021) vs. CAR-T (2018-2021) using the Center for International Blood & Marrow Transplant Research registry. Median follow-up was 49.7 months for the auto-HCT and 24.7 months for the CAR-T cohort. Patients ages 18 and 75 with a diagnosis of DLBCL were included if they received auto-HCT (n = 281) or commercial CAR-T (n = 79) while in a CR. Patients undergoing auto-HCT with only one prior therapy line and CAR-T patients with a previous history of auto-HCT treatment were excluded. Endpoints included Progression-free survival (PFS), relapse rate, non-relapse mortality (NRM) and overall survival (OS). In univariate analysis, treatment with auto-HCT was associated with a higher rate of 2-year PFS (66.2% vs. 47.8%; p < 0.001), a lower 2-year cumulative incidence of relapse (27.8% vs. 48% ; p < 0.001), and a superior 2-year OS (78.9% vs. 65.6%; p = 0.037). In patients with early (within 12 months) treatment failure, auto-HCT was associated with a superior 2-year PFS (70.9% vs. 48.3% ; p < 0.001), lower 2-year cumulative incidence of relapse (22.8% vs. 45.9% ; p < 0.001) and trend for higher 2-year OS (82.4% vs. 66.1% ; p = 0.076). In the multivariable analysis, treatment with auto-HCT was associated with a superior PFS (hazard ratio 1.83; p = 0.0011) and lower incidence of relapse (hazard ratio 2.18; p < 0.0001) compared to CAR-T. In patients with relapsed LBCL who achieve a CR, treatment with auto-HCT is associated with improved clinical outcomes compared to CAR-T. These data support the consideration of auto-HCT in select patients with LBCL achieving a CR in the relapsed setting.

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Is autologous transplant in relapsed DLBCL patients achieving only a PET+ PR appropriate in the CAR T-cell era?

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