HLA-DR expression on monocytes and outcome of anti-CD19 CAR T-cell therapy for large B-cell lymphoma.

Despite their unprecedented success in relapsed/refractory (R/R) large B-cell lymphoma (LBCL), anti-CD19 CAR T cells are associated with significant toxicity, and more than half of patients relapse. As monocytes emerged as key players in CAR therapy, we sought to evaluate the evolution of HLA-DR expression on monocytes (mHLA-DR) before and after commercial anti-CD19 CAR T-cell infusion in a large cohort (n = 103) of patients with R/R LBCL and its association with adverse events and treatment response. Cy-Flu-based lymphodepletion (LD) upregulated mHLA-DR in 79% of the cases, whereas in 2l% of cases (15 patients), the mHLA-DR level decreased after LD, and this decrease was associated with poorer outcome. Low mHLA-DR at day minus 7 (D-7) (<13 500 antibodies per cell) before CAR T-cell infusion correlated with older age, poorer performance status, higher tumor burden, and elevated inflammatory markers. With a median follow-up of 7.4 months, patients with low mHLA-DR D-7 exhibited a poorer duration of response and survival than the higher mHLA-DR D-7 group. For toxicity management, tocilizumab was more frequently used in the low-mHLA-DR D-7 group. These data suggest that monocyte dysregulation before LD, characterized by the downregulation of mHLA-DR, correlates with an inflammatory and immunosuppressive tumor environment and is associated with failure of anti-CD19 CAR T cells in patients with R/R LBCL. Modulation of these myeloid cells represents a promising field for improving CAR therapy.

Lymphoma diagnosis: lessons learned from the comparison of histology and cytology associated with flow cytometry.

For lymphoma diagnosis, the flow cytometry (FCM) and cytology associated with FCM (C-FCM) performed on fine needle aspiration (FNA) or cell suspension/imprints from fresh tissue display a good concordance (from 85 to 90%) with the diagnosis made using histological data. Herein is reported a retrospective series of discordant cases, five of them are discussed in details, and some recommendations are proposed for the interpretation of C-FCM data. Firstly, this review highlights the importance of analyzing simultaneously the cytological and FCM data. In particular, the cytological data are crucial to interpret FCM data and/or to complete Ab panels when the strategy of the laboratory is to systematically perform a first screening, which don't always allow the detection of lymphoma cells. Secondly, this report underlines that cytology and FCM analysis should be followed by a confrontation/discussion with a pathologist. Finally, C-FCM appears to be a rapid and particularly important technic to guide the choice of the following diagnosis tools (IHC and genetic).

Rituximab in combination with adapted-dose of ifosfamide and etoposide as salvage treatment in elderly refractory/relapsed diffuse large B-cell lymphoma patients non-candidate for high dose therapy: a retrospective study.

We retrospectively reviewed for 72 relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) patients ineligible for autologous stem-cell transplantation (ASCT) treated between 2004 and 2017, efficacy and safety profile of rituximab (375 mg/m2) in combination with etoposide (300 mg/m2) and ifosfamide (1500 mg/m2) at 2, 3, or 4-week intervals. Median age was 79 years (range, 64-92). The median number of previous line was 1 (range 1-8). Patients received a median of six cycles (1-12). Fourteen patients (19%) presented partial and 14 complete responses (19%). Among the 369 cycles, nine patients developed febrile neutropenia (13%), 14 a grade 3-4 neutropenia (19%), 7 a grade 3-4 thrombocytopenia (10%) without grade 3-4 non-hematological toxicity. With a median follow up of 7.8 months, the median progression-free survival, overall survival, and duration of response were 4.4 months, 9.4 months, and 12 months, respectively. This regimen represents a therapeutic option in R/R DLBCL patients ineligible to ASCT.

Composite and sequential lymphoma between classical Hodgkin lymphoma and primary mediastinal lymphoma/diffuse large B-cell lymphoma, a clinico-pathological series of 25 cases.

Composite and sequential lymphomas involving both classical Hodgkin lymphoma (CHL) and primary mediastinal B-cell lymphoma (PMBCL) are rare phenomena. Beyond the relevant biological interest raised by these cases, treatments and outcome data are poorly covered in the recent literature. This retrospective analysis describes the pathological and clinical characteristics of 10 composite and 15 sequential cases included after a central pathological review. At diagnosis, 70% of the composite lymphomas presented a disseminated and extranodal disease. Among the 15 sequential lymphomas, 12 were CHL at first occurrence and three were PMBCL. Based on their clinical evolution, these sequential lymphomas could be divided into early (i.e., diagnosis of second lymphoma within a year) and late [(i.e., a second lymphoma occurrence occurring after a long period of complete remission]). All composite cases were alive in complete remission after a median follow-up of 34 months. If the early sequential lymphoma presented a particularly poor outcome with a median overall survival shorter than one year, the late cases were efficiently salvaged. Further molecular studies are needed to describe the underlying biology of these rare diseases, possibly representing the extreme of tumour cell plasticity found in grey-zone lymphoma.