Large B-cell lymphomas (LBCL) are the most common types of non-Hodgkin lymphoma. Although outcomes have improved thanks to the introduction of rituximab-based chemoimmunotherapy, certain LBCL still represents a challenge because of initial resistance to therapy or recurrent relapses. Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are second-generation autologous CD19-targeted chimeric antigen receptor (CAR) T-cell therapies approved for patients with relapsed/refractory (R/R) LBCL, based on the results of phase II pivotal single-arm trials ZUMA-1 (for axi-cel) and JULIET (for tisa-cel). Here, we report patients outcomes with axi-cel and tisa-cel in the standard of care (SoC) setting for R/R LBCL, treated at our Institution. Data were collected from patients who underwent leukapheresis between August 2019 and February 2021. Toxicities were graded and managed according to the institution’s guidelines. Responses were assessed as per Lugano 2014 classification. Of the 30 patients who underwent leukapheresis, 18 (60%) received axi-cel, while 12 (40%) tisa-cel. Grade 3 or higher cytokine release syndrome and neurotoxicity occurred in 10% and 16% patients, respectively. Best objective and complete response rates were 73.3% and 40%, respectively. Treatment in SoC setting with CD19 CAR T-cell therapies for R/R LBCL showed a manageable safety profile and high objective response rate.

A significant body of literature has been generated related to the detection of measurable residual disease (MRD) at the time of achieving complete remission (CR) in patients with hairy cell leukemia (HCL). However, due to the indolent nature of the disease as well as reports suggesting long-term survival in patients treated with a single course of a nucleoside analog albeit without evidence of cure, the merits of detection of MRD and attempts to eradicate it have been debated. Studies utilizing novel strategies in the relapse setting have demonstrated the utility of achieving CR with undetectable MRD (uMRD) in prolonging the duration of remission. Several assays including immunohistochemical analysis of bone marrow specimens, multi-parameter flow cytometry and molecular assays to detect the mutant BRAF V600E gene or the consensus primer for the immunoglobulin heavy chain gene (IGH) rearrangement have been utilized with few comparative studies. Here we provide a consensus report on the available data, the potential merits of MRD assessment in the front-line and relapse settings and recommendations on future role of MRD assessment in HCL.

Marginal zone lymphomas are indolent diseases. Overall survival rates are very good, but patients tend to relapse and may do so several times. The concept of treatment sequencing is therefore important and necessary to preserve adequate organ function and to avoid excessive toxicity, with the final goal of achieving long survival times. Systemic treatments and chemotherapy are considered to be an option in multiply relapsing disease, in cases that are in an advanced stage at presentation or relapse, and in cases where initial local treatments lack efficacy. Targeted agents and new drugs can provide chemotherapy-free alternatives in heavily pretreated patients.