Total immunotherapy for Hodgkin lymphoma

International audienceThe anti-CD30 antibody-drug conjugate brentuximab vedotin and the programmed cell death 1 (PD-1) monoclonal antibodies nivolumab and pembrolizumab have dramatically improved outcomes for patients with relapsed or refractory classic Hodgkin lymphoma. With the goal of improving the depth and duration of remissions with these drugs, combination strategies investigating various combination partners are underway, including conventional chemotherapy and other checkpoint inhibitors. Trials investigating the combination of nivolumab and brentuximab vedotin in first and second-line settings showed a significant improvement in complete response rate compared with treatment with either nivolumab or brentuximab vedotin alone, suggesting the potential of this approach

Immune and Cell Therapy in Non-Hodgkin Lymphoma

International audienceThe promise of immunotherapy has shone brightly for decades in hematologic malignancies and specifically in non-Hodgkin lymphoma. The last decade has witnessed the emergence of completely novel forms of immunotherapy, including immune checkpoint blockade, bispecific antibodies, and chimeric antigen receptor T cells. These treatments have shown phenomenal, and in some cases possibly curative, successes in various relapsed/refractory lymphomas. This review summarizes the most notable successes and promising findings as well as some of the attendant failures. These treatments will doubtlessly transform the treatment paradigms across many lymphoma subtypes. Yet, only if we can better understand their mechanisms of action, toxicity, and resistance will be able to maximize their therapeutic benefit

Interim FDG-PET/CT for Response Assessment of Lymphoma

The clinical use and prognostic value of interim FDG-PET/CT (iPET/CT), which is performed after treatment initiation but prior to its completion, varies by lymphoma subtype. Evidence supporting the prognostic value of iPET/CT is more robust for classical Hodgkin lymphoma (cHL), and in this lymphoma subtype, response-adapted treatment approaches guided by iPET/CT are a widely used standard of care for first-line therapy. The data supporting use of iPET/CT among patients with non-Hodgkin lymphoma (NHL) is less well-established, but failure to achieve complete metabolic response on iPET/CT is generally considered a poor prognostic factor with likely consequences for progression free survival. This review will present the available evidence supporting use of iPET/CT in lymphoma patients, particularly as it relates to prognostication and the ability to inform response-adapted treatment strategies. The latter will be addressed through a discussion on the major iPET-response adapted clinical trials with mention of ongoing trials. Special attention will be given to cHL and a few subtypes of NHL, including diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and peripheral T cell lymphoma (PTCL)

Autologous transplant vs chimeric antigen receptor T-cell therapy for relapsed DLBCL in partial remission

The relative efficacy of autologous hematopoietic cell transplant (auto-HCT) vs chimeric antigen receptor T-cell (CAR-T) therapy in patients with diffuse large B-cell lymphoma (DLBCL) who achieve a partial remission (PR) after salvage chemotherapy is not known. Using the Center for International Blood & Marrow Transplant Research registry database, we identified adult patients with DLBCL who received either an auto-HCT (2013-2019) or CAR-T treatment with axicabtagene ciloleucel (2018-2019) while in a PR by computed tomography or positron emission tomography scan. We compared the clinical outcomes between the 2 cohorts using univariable and multivariable regression models after adjustment for relevant baseline and clinical factors. In the univariable analysis, the 2-year progression-free survival (52% vs 42%; P = .1) and the rate of 100-day nonrelapse mortality (4% vs 2%; P = .3) were not different between the 2 cohorts, but consolidation with auto-HCT was associated with a lower rate of relapse/progression (40% vs 53%; P = .05) and a superior overall survival (OS) (69% vs 47%; P = .004) at 2 years. In the multivariable regression analysis, treatment with auto-HCT was associated with a significantly lower risk of relapse/progression rate (hazard ratio = 1.49; P = .01) and a superior OS (hazard ratio = 1.63; P = .008). In patients with DLBCL in a PR after salvage therapy, treatment with auto-HCT was associated with a lower incidence of relapse and a superior OS compared with CAR-T. These data support the role of auto-HCT as the standard of care in transplant-eligible patients with relapsed DLBCL in PR after salvage therapy

Autologous transplant vs. CAR-T therapy in patients with DLBCL treated while in complete remission

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