An early PET scan after two cycles of treatment can effectively predict the outcome in patients with DLBCL treated with rituximab and anthracycline-based chemotherapy by using either a visual or quantitative approach.
Two autologous anti-CD19 chimeric antigen receptors (CAR) T cells (axicabtagene ciloleucel [axi-cel] and tisagenlecleucel [tisa-cel]) are commercially approved in Europe for relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). We performed a retrospective study to evaluate patterns of use, efficacy and safety for axi-cel and tisa-cel. Data from 70 patients who underwent apheresis for commercial CAR T cells between January 2018 and November 2019 in our institution were retrospectively collected. Sixty-one patients were infused. The median age at infusion was 59 years old (range 27-75 years). The median number of prior therapies was 3 (range, 2-6). The overall response rates (ORRs) at 1 month and 3 months were 63% and 45%, respectively, with 48% and 39% achieving a complete response (CR), respectively. After a median follow-up after infusion of 5.7 months, the median progression-free survival (PFS) was 3.0 months (95% CI, 2.8-8.8 months), and the median overall survival (OS) was 11.8 months (95% CI, 6.0-12.6 months). In multivariate analysis, factors associated with poor PFS were the number of previous lines of treatment before CAR T cells (≥4) (P = .010) and a C reactive protein (CRP) value >30 mg/L at the time of lymphodepletion (P < .001). Likewise, the only factor associated with a shorter OS was CRP >30 mg/L (P = .009). Cytokine release syndrome (CRS) of any grade occurred in 85% of patients, including 8% of patients with CRS of grade 3 or higher. Immune cell-associated neurotoxicity syndrome (ICANS) of any grade occurred in 28% of patients, including 10% of patients with ICANS of grade 3 or higher. Regarding efficacy and safety, no significant difference was found between axi-cel and tisa-cel. This analysis describes one of the largest real-life cohorts of patients treated with axi-cel and tisa-cel for R/R aggressive B cell lymphoma in Europe.
Polatuzumab vedotin plus bendamustine and rituximab (pola+BR) received regulatory approvals in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) based on primary results from the randomized arms of the GO29365 study. Following the randomized phase, 106 additional patients received pola+BR in a single-arm extension cohort. We report updated results from the randomized arms, and results of the extension cohort. In this phase Ib/II study, patients with R/R DLBCL who were transplant-ineligible received up to six 21-day cycles of pola+BR or BR. The primary endpoint of the randomized arms was complete response (CR) rate at end of treatment. Primary objectives of the extension cohort were safety, pharmacokinetics, and efficacy of pola+BR. As of July 7, 2020, 192 patients with R/R DLBCL were enrolled into pola+BR cohorts (n=152 [safety run-in: n=6; randomized: n=40; extension cohort: n=106]) or the BR cohort (n=40). Significant survival benefit with pola+BR versus BR persisted in the randomized arms (median progression-free survival [PFS]: 9.2 vs 3.7 months, hazard ratio [HR]: 0.42, 95% confidence interval [CI] 0.25-0.71 months; median overall survival [OS]: 12.4 vs 4.7 months, HR: 0.42, 95% CI 0.24-0.72 months). In the extension cohort, the independent review committee (IRC)-assessed objective response rate was 41.5% and CR rate was 38.7%; median IRC-assessed PFS and OS were 6.6 months and 12.5 months, respectively. No new safety signals with pola+BR were identified. Pola+BR is an effective treatment option for patients with R/R DLBCL, with a well-characterized and manageable safety profile. ClinicalTrials.gov: NCT02257567.
In this retrospective study, we report 70 cases of Epstein-Barr virus (EBV)+ diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) among 1696 DLBCL-NOS cases diagnosed between 2006 and 2019 (prevalence of 4.1%). At diagnosis, median age was 68.5 years; 79% of the cases presented with an advanced-stage disease (III-IV), 48% with extranodal lesions, and 14% with an hemophagocytic lymphohistiocytosis (HLH) (8 at diagnosis and 1 on therapy). A total of 46 cases presented a polymorphic pattern, and 21 were monomorphic. All had a non-germinal center B phenotype, with the majority of tumor cells expressing CD30 and programmed death ligand 1 (98% and 95%, respectively). Type II and III EBV latency was seen in 88% and 12% of the cases, respectively. Patients were treated with immunochemotherapy (59%) or chemotherapy (22%), and 19% received palliative care due to advanced age and altered performance status. After a median follow-up of 48 months, progression-free survival (PFS) and overall survival (OS) at 5 years were 52.7% and 54.8%, respectively. Older age (>50 years) and HLH were associated with shorter PFS and OS in multivariate analysis (PFS: hazard ratio [HR], 14.01; 95% confidence interval [CI], 2.34-83.97; and HR, 5.78; 95% CI, 2.35-14.23; OS: HR, 12.41; 95% CI, 1.65-93.53; and HR, 6.09; 95% CI, 2.42-15.30, respectively). Finally, using a control cohort of 425 EBV− DLBCL-NOS, EBV positivity was associated with a shorter OS outcome within patients >50 years (5-year OS, 53% [95% CI, 38.2-74] vs 60.8% [95% CI, 55.4-69.3], P = .038), but not in younger patients.
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