Early failure is still a poor prognostic factor in patients with relapsed or refractory large B-cell lymphoma in the era of CAR T-cell therapy.

Patients with refractory or relapsed (R/R) large B-cell lymphoma (LBCL) refractory to first-line chemotherapy or with early relapse have poor outcomes. While chimeric antigen receptor (CAR) T-cell therapy has impressive efficacy after two or more lines of chemotherapy, it's still uncertain if these outcomes remain consistent in the context of third-line CAR T-cell therapy. We conducted a retrospective study of 107 R/R LBCL patients. Patients with relapse 12 months or more after their first-line chemoimmunotherapy (late failure: n = 25) had significantly longer overall survival (OS) than patients with refractory disease or relapse within 12 months (early failure: n = 82) (median OS: not achieved vs. 18.4 months; P < 0.001). Among patients who proceeded to autologous hematopoietic stem-cell transplantation (auto-HSCT), those with late failure had significantly longer event-free survival (EFS) than those with early failure (median EFS: 26.9 vs. 3.1 months; P = 0.012). However, no significant difference in EFS was detected among patients who underwent CAR T-cell therapy (median EFS: not reached vs. 11.8; P = 0.091). Cox regression with restricted cubic spline demonstrated that timing of relapse had significant impact on EFS in patients with auto-HSCT but not in patients with CAR T-cell therapy. Of patients who were scheduled for CAR T-cell therapy, those with late failure were significantly more likely to receive CAR T-cell therapy than those with early failure (90% vs. 57%; P = 0.008). In conclusion, patients with early failure still experienced poor outcomes after the approval of third-line CAR T-cell therapy.

[Polatuzumab vedotin, bendamustine, and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma, including the outcome as a bridging treatment to CAR-T cell therapy or allogeneic hematopoietic stem cell transplant].

Pola-BR (polatuzumab vedotin, bendamustine, and rituximab) therapy received approval for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) in Japan in March 2021. There have been few reports on the efficacy and safety of Pola-BR therapy in Japanese clinical practice. A retrospective analysis was performed on twenty-nine patients with R/R DLBCL who received Pola-BR therapy at our institution (intent to cellular immunotherapy cohort: 20 patients, stand-alone treatment cohort: nine patients). The overall response rate was 69.0% (complete response 27.6%). The median progression-free survival was 5.1 months, with a 9.5-month median overall survival. In the intent to cellular immunotherapy cohort, 11 of 19 patients received chimeric antigen receptor T-cell (CAR-T) infusions, and one patient received allogeneic stem cell transplantation. Four patients received Pola-BR therapy, including bendamustine before leukapheresis, and all produced CAR-T products successfully. 3 of the 28 patients experienced grade3 or higher adverse events, and two required treatment discontinuation. Our single institution, a real-world cohort of R/R DLBCL patients showed high efficacy outcomes and a tolerable toxicity profile for Pola-BR therapy, which is comparable to previous studies. More cases are needed to determine its impact on CAR-T therapy and stem cell transplantation.

Hemoglobin-platelet index as a prognostic factor in patients with peripheral T-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with a poor prognosis. The International Prognostic Index (IPI) and the Prognostic Index for PTCL-unspecified (PIT) is used to predict the prognosis of PTCL. The hemoglobin-platelet index (HPI), based on anemia and thrombocytopenia status, is associated with the prognosis of diffuse large B-cell lymphoma. However, its significance in terms of predicting the prognosis of PTCL has not been fully investigated. We herein retrospectively analyzed 100 patients with newly diagnosed PTCL in our department. At a median follow-up of 3.2 years, the median progression-free survival (PFS) and overall survival (OS) was 0.72 (95% confidence interval [CI]: 0.56-1.2) years and 2.0 (95% CI: 1.5-4.7) years, respectively. Multivariate analysis revealed that elevated lactic dehydrogenase (LDH) and hypoalbuminemia were independent adverse variables for PFS. The HPI showed significant predictive value for both PFS and OS. As a new prognostic model comprising the HPI, LDH, and albumin, the LA-HPI allowed the stratification of patients into four distinct risk subgroups: low risk (zero risk factors), low-intermediate risk (one risk factors), high-intermediate risk (two or three risk factors), or high risk (four risk factors). The PFS and OS differed significantly among the patients by the LA-HPI score. The LA-HPI demonstrated better predictive performance compared to the IPI, PIT, and HPI. Our data demonstrated the prognostic utility of the HPI in patients with PTCL. The LA-HPI, incorporating four readily obtainable parameters, exhibited superior performance compared to traditional indices.

Clinical outcomes in transplant-eligible patients with relapsed or refractory diffuse large B-cell lymphoma after second-line salvage chemotherapy: A retrospective study.

OBJECTIVE: The prognosis of patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) is poor. Although patients who fail first-line salvage chemotherapy are candidates for second-line salvage chemotherapy, the optimal treatment strategy for these patients has not yet been established. METHODS: The present, single-center, retrospective study included transplant-eligible patients with R/R DLBCL who received second-line salvage chemotherapy with curative intent. RESULTS: Seventy-six patients with R/R DLBCL received second-line salvage chemotherapy. Eighteen (23.7%) patients were responders to the first-line salvage chemotherapy. The overall response rate was 39.5%, and overall survival (OS) was significantly longer in patients who responded to second-line salvage chemotherapy than those who did not. Forty-one patients who proceeded to potentially curative treatment (autologous hematopoietic stem cell transplantation [ASCT], chimeric antigen receptor [CAR] T-cell therapy, or allogeneic hematopoietic stem cell transplantation) had a better prognosis than those who did not. Among the 46 patients who failed to respond to the second-line salvage regimen, only 18 (39.1%) could proceed to the curative treatments. However, among the 30 patients who responded to the second-line salvage regimen, 23 (76.7%) received one of the potentially curative treatments. Among 34 patients who received CAR T-cell therapy, OS was significantly longer in those who responded to salvage chemotherapy immediately prior to CAR T-cell therapy than in those who did not respond. In contrast, the number of prior lines of chemotherapy was not identified as a statistically significant prognostic factor of survival. No significant difference was detected in OS between patients receiving ASCT and those receiving CAR T-cell therapy after the response to second-line salvage chemotherapy. DISCUSSION: In this study, we demonstrated that chemosensitivity remained a crucial factor in predicting survival outcomes following CAR T-cell therapy irrespective of the administration timing, and that both ASCT and CAR T-cell therapy were acceptable after the response to second-line salvage chemotherapy.

Utility of the frailty score for predicting prognosis and individualizing treatment intensity in elderly patients with diffuse large B cell lymphoma.

The optimal dose intensity of chemotherapy for elderly patients with diffuse large B cell lymphoma (DLBCL) remains controversial because of concerns about adverse events and comorbidities related to the patients' frailty. This single-center study retrospectively analyzed patients aged ≥ 70 years who were newly diagnosed with DLBCL and received chemotherapy between 2004 and 2022. Survival outcomes and treatment-related mortality (TRM) were stratified according to geriatric assessment variables, and the influence of chemotherapy dose intensity on outcomes was assessed using the frailty score with a Cox hazards model with restricted cubic spline (RCS) in patients aged 70-79 years. In total, 337 patients were included. The frailty score accurately predicted prognosis (5-year overall survival [OS]: 73.1%, 60.2%, and 29.7% in fit, unfit, and frail patients, respectively; P < 0.001) and TRM (5-year TRM: 0%, 5.4%, and 16.8 in fit, unfit, and frail patients, respectively; P < 0.001). Cox regression with RCS demonstrated a linear association between dose intensity and survival outcomes. Initial dose intensity (IDI) and relative dose intensity (RDI) had a significant impact on OS in fit patients. However, IDI and RDI had no significant effect on survival in non-fit (unfit and frail) patients. The frailty score identified non-fit patients with poorer survival and a higher risk of TRM. While fit patients were likely to benefit from full-dose R-CHOP, unfit and frail patients would likely benefit more from attenuated R-CHOP. This study suggested a potential role for the frailty score in individualizing treatment intensity in elderly patients with DLBCL.

[Tisagenlecleucel for relapsed/refractory diffuse large B-cell lymphoma: real-world data from single institute experience].

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the approach to patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study retrospectively analyzed patients treated with commercially available tisagenlecleucel at our hospital and evaluated its safety and effectiveness. Of the 21 patients evaluated, any grade and grade ≥3 cytokine release syndrome (CRS) occurred in 85.7% and 9.5% of the patients, respectively. A total of 66.7% received tocilizumab and 28.6% received glucocorticoids for the treatment of CRS. The complete response (CR) rate at 3 months was 61.9% (95% confidence interval [CI] 38.4-81.9). After a median follow-up of 6.3 months following CAR-T infusion, the progression-free survival (PFS) and overall survival rates at 6 months were 53.1% (95%CI 28.3-72.7) and 69.2% (95%CI 43.7-84.9), respectively. Severe cytopenia and hypogammaglobulinemia occurred frequently following CAR-T infusion. Eight patients (38.1%) had comorbidities that would have made them ineligible for leukapheresis in the JULIET trial. However, the presence of comorbidities at the time of leukapheresis had no significant effect on the rates of CR, PFS, and adverse events. Tisagenlecleucel for r/r DLBCL in the real-world setting showed high efficacy and manageable safety profile comparable with the pivotal trial.