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CD19-directed chimeric antigen receptor (CAR) T cells have evolved as a new standard-of-care (SOC) treatment in patients with relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Here, we report the first German real-world data on SOC CAR T-cell therapies with the aim to explore risk factors associated with outcomes. Patients who received SOC axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) for LBCL and were registered with the German Registry for Stem Cell Transplantation (DRST) were eligible. The main outcomes analyzed were toxicities, response, overall survival (OS), and progression-free survival (PFS). We report 356 patients who received axi-cel (n = 173) or tisa-cel (n = 183) between November 2018 and April 2021 at 21 German centers. Whereas the axi-cel and tisa-cel cohorts were comparable for age, sex, lactate dehydrogenase (LDH), international prognostic index (IPI), and pretreatment, the tisa-cel group comprised significantly more patients with poor performance status, ineligibility for ZUMA-1, and the need for bridging, respectively. With a median follow-up of 11 months, Kaplan-Meier estimates of OS, PFS, and nonrelapse mortality (NRM) 12 months after dosing were 52%, 30%, and 6%, respectively. While NRM was largely driven by infections subsequent to prolonged neutropenia and/or severe neurotoxicity and significantly higher with axi-cel, significant risk factors for PFS on the multivariate analysis included bridging failure, elevated LDH, age, and tisa-cel use. In conclusion, this study suggests that important outcome determinants of CD19-directed CAR T-cell treatment of LBCL in the real-world setting are bridging success, CAR-T product selection, LDH, and the absence of prolonged neutropenia and/or severe neurotoxicity. These findings may have implications for designing risk-adapted CAR T-cell therapy strategies., (© 2022 by The American Society of Hematology.)

The optimal treatment of patients with relapsed or refractory nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is ill defined. To shed more light on treatment options and outcome, we performed an analysis using the database of the German Hodgkin Study Group (GHSG). Ninety-nine patients who had received first-line treatment within 12 prospective GHSG studies conducted between 1993 and 2009, and subsequently developed disease recurrence (n = 91) or had primary disease progression (n = 8), were included. At initial NLPHL diagnosis, the median age was 40 years and 76% of patients were male. First-line treatment consisted of radiotherapy (RT) alone (20%), chemotherapy with or without RT (74%), and the anti-CD20 antibody (Ab) rituximab (6%), respectively. The median follow-up from initial diagnosis was 11.2 years. The median time to disease recurrence was 3.7 years. The applied salvage approaches included single-agent anti-CD20 Ab treatment or RT alone (37%), conventional chemotherapy (CT) with or without anti-CD20 Ab treatment with or without RT (27%) and high-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) (31%). No salvage treatment was given in 4% of patients. The 5-year progression-free survival and overall survival estimates after NLPHL recurrence were 75.6% and 89.5% (74.1% and 97.2% after single-agent anti-CD20 Ab treatment or RT alone; 68.0% and 77.8% after CT with or without anti-CD20 Ab treatment with or without RT; 84.6% and 89.8% after HDCT and ASCT). Hence, patients with relapsed or refractory NLPHL had a good overall prognosis. Factors such as time to disease recurrence and previous treatment may guide the choice of the optimal salvage approach for the individual patient., (© 2018 by The American Society of Hematology.)

Therapy-related acute myeloid leukemia and myelodysplastic syndromes (t-AML/MDS) represent severe late effects in patients treated for Hodgkin lymphoma (HL). Because more recent data are scarce, we retrospectively analyzed incidence, outcome, and risk factors for the development of t-AML/MDS after HL. A total of 11,952 patients treated for newly diagnosed HL within German Hodgkin Study Group trials between 1993 and 2009 were considered. At a median follow-up of 72 months, t-AML/MDS was diagnosed in 106/11,952 patients (0.9%). Median time from HL treatment to t-AML/MDS was 31 months. The median age of patients with t-AML/MDS was higher than in the whole patient group (43 vs 34 years, P < .0001). Patients who received 4 or more cycles of BEACOPP(escalated) had an increased risk to develop t-AML/MDS when compared with patients treated with less than 4 cycles of BEACOPP(escalated) or no BEACOPP chemotherapy (1.7% vs 0.7% vs 0.3%, P < .0001). The median overall survival (OS) for all t-AML/MDS patients was 7.2 months. However, t-AML/MDS patients proceeding to allogeneic stem cell transplantation had a significantly better outcome with a median OS not reached after a median follow-up of 41 months (P < .001).