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Patients with high-risk diffuse large B-cell lymphoma (DLBCL) have poor outcomes following first-line cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (R-CHOP). Evidence shows chemotherapy and immune checkpoint blockade can increase antitumor efficacy. This study investigated durvalumab, a programmed death-ligand 1 inhibitor, combined with R-CHOP or lenalidomide + R-CHOP (R 2 -CHOP) in newly diagnosed high-risk DLBCL. Patients received durvalumab 1125 mg every 21 days for 2-8 cycles + R-CHOP (non-activated B-cell [ABC] subtype) or R 2 -CHOP (ABC), then durvalumab consolidation (1500 mg every 28 days). Of 46 patients, 43 received R-CHOP and three R 2 -CHOP. All patients had the high-risk disease; 14 (30.4%) and eight (17.4%) had double- or triple-hit DLBCL, respectively. Following induction, 20/37 (54.1%) patients receiving durvalumab + R-CHOP achieved complete response (CR), and seven (18.9%) partial response (PR); 25 (67.6% [95% CI 50.2-82.0]) continued to consolidation and were progression-free at 12 months. Among efficacy-evaluable patients with double- or triple-hit DLBCL (n = 12), five achieved CR and five PR. Adverse events were generally consistent with R-CHOP. Correlative analyses did not identify conclusive biomarkers of response. Durvalumab + R-CHOP is feasible in DLBCL with no new safety signals, but the combination provided no greater benefit than R-CHOP., (© 2021. Japanese Society of Hematology.)

Mid-infrared (MIR) microscopic imaging of indolent and aggressive lymphomas was performed including formalin-fixed and paraffin-embedded samples of six follicular lymphomas and 12 diffuse large B-cell-lymphomas as well as reactive lymph nodes to investigate benefits and challenges for lymphoma diagnosis. MIR images were compared to defined pathological characteristics such as indolent versus aggressive versus reactive, germinal centre versus activated cell-of-origin (COO) subtypes, or a low versus a high proliferative index and level of PD-L1 expression. We demonstrated that MIR microscopic imaging can differentiate between reactive lymph nodes, indolent and aggressive lymphoma samples. Also, it has potential to be used in the subtyping of lymphomas, as shown with the differentiation between COO subtypes, the level of proliferation and PD-L1 expression. MIR microscopic imaging is a promising tool for diagnosis and subtyping of lymphoma and further evaluation is needed to fully explore the advantages and disadvantages of this method for pathological diagnosis., (© 2021 The Authors. Journal of Biophotonics published by Wiley-VCH GmbH.)

High-grade B cell lymphomas with rearrangements on C-MYC and BCL2 and/or BCL6 (HGBL with MYC and BCL2 and/or Bcl6 rearrangement) are associated with worse clinical outcomes and thus were introduced as a separate new category in the recently updated WHO classification. From 2012 to 2016, we analyzed a consecutive cohort of large B cell lymphomas (LBCLs) for C-MYC, BCL2, and BCL6 rearrangements and correlated our results with clinical-pathological parameters. Ten of 78 (13%) cases had a C-MYC and BCL2 and/or BCL6 rearrangement, so-called double or triple hit (DH), while double/triple copy number gains (CNGs) were found in eight (10%) patients. Patients with a high-grade lymphoma with DH or CNG progressed significantly more often after first-line chemotherapy (p = 0.005). When treated with standard chemotherapy, patients with a DH or CNG had a significantly worse overall (OS) and recurrence free survival (RFS) compared with all other patients (p = 0.033 and p < 0.001, respectively). Thus, patients with a diffuse large B cell lymphoma, harboring a double/triple CNG, seem to have a similar poor prognosis than those with a DH. Though our data can only be regarded as preliminary, our results warrant further investigations to fully elucidate the role of CNGs as well as underlying molecular mechanisms resulting in aggressive behavior in LBCL.

Background: Despite the advent of new treatment strategies, many patients with diffuse large B-cell lymphoma (DLBCL) relapse or die of the disease. Prospective clinical trials have demonstrated that lenalidomide is an effective and safe treatment option, especially for non-germinal center B-cell (non-GCB) DLBCL. However, routine clinical data are lacking, which is why we provide the results of the so-far largest relapsed/refractory (R/R) DLBCL real-life analysis., Methods: We retrospectively assessed 123 R/R DLBCL patients who received either 15 or 25 mg/day of lenalidomide from January 2006 to January 2015., Results: During a median follow-up period of 4.5 years, complete remission was achieved in 32% and a partial remission in 33% non-GCB patients compared with 0% and 3% in the GCB group (p < .001 and .001, respectively), with median response durations of 15 and 5 months, respectively (p < .001). Lenalidomide at 25 mg was superior to 15 mg in terms of response (complete remission 21% and partial remission 23% vs. 0% and 8%; p = .007 and .05) and median response duration (10 vs. 4 months; p = .03). Toxicity was limited and reversible. Median progression-free survival differed between non-GCB and GCB patients (37 vs. 30 months; p < .001) and between the two dosages (24 vs. 34 months; p = .002). However, overall survival was similar between the subgroups (38-42 months)., Conclusion: We provide evidence that lenalidomide is a valid treatment option for R/R DLBCL, with limited and reversible toxicity, and is more efficient in non-GCB DLBCL and at higher doses., Implications for Practice: Despite the advent of new treatment strategies, many patients with diffuse large B-cell lymphoma (DLBCL) relapse or die of the disease; hence, novel therapeutic approaches are urgently needed. This study confirms that lenalidomide is a valid and well-tolerated treatment option for relapsed/refractory (R/R) DLBCL. Superior outcomes were observed in non-germinal center B-cell (GCB) DLBCL, probably because of inhibition of the nuclear factor-κB pathway. Similarly, high drug doses resulted in greater clinical benefits. Overall, lenalidomide is a suitable therapeutic option for R/R DLBCL, especially in non-GCB DLBCL, and 25 mg/day dosing should be preferred., Competing Interests: of potential conflicts of interest may be found at the end of this article., (©AlphaMed Press.)

Background: Chemoimmunotherapy containing rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) is the standard treatment for diffuse large B-cell lymphoma (DLBCL). Doxorubicin may induce early and late cardiotoxicity. Non-pegylated liposomal (NPL) doxorubicin may reduce cardiotoxicity., Patients and Methods: Patients with untreated CD20+ DLBCL were randomised to conventional R-CHOP chemoimmunotherapy or rituximab, cyclophosphamide, non-pegylated liposomal doxorubicin, vincristine and prednisolone (R-COMP) with doxorubicin substituted by NPL-doxorubicin. Left ventricular ejection fraction (LVEF) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were measured before each treatment cycle and after the end of treatment., Results: The mean LVEF of 178 and 158 measurements in the R-COMP and R-CHOP arms was 63.31% and 62.25%, respectively (P = 0.167). During treatment the LVEF measurements were below 50% in 10/218 (4.6%) in the R-COMP arm and 31/196 (15.8%) in the R-CHOP arm (P<0.001). Thirty-six of 40 (90%) patients in the R-COMP arm, but only 24/36 (66.7%) in the R-CHOP arm had all NT-proBNP levels below 400 pg/ml during and at the end of treatment (P = 0.013). There were more serious adverse events in the R-CHOP arm (26 versus 40, P = 0.029). Infections were more common (15 versus 28) in the R-CHOP arm., Interpretation: In patients with normal cardiac function, six cycles of R-CHOP resulted in a low rate of early cardiotoxicity. NPL-doxorubicin did not reduce cardiotoxicity, although cardiac safety signals were elevated in R-CHOP compared to R-COMP., Funding: Cephalon provided the Arbeitsgemeinschaft Medikamentöse Tumortherapie with NPL-doxorubicin and an unrestricted grant, but was not involved in the study protocol, data acquisition, data analysis or the writing of the paper., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Diffuse large B-cell lymphoma (DLBCL) is a rather aggressive disease and the natural course of this lymphoma is very dismal. However, first the introduction of anthracycline-containing chemotherapy regimens and then the addition of rituximab were important steps forward. Since no complete real-life analyses have yet been published, we analyzed all patients with DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in the whole region of Tyrol and compared the results to a historical CHOP(-like)-treated cohort. Two hundred and nineteen consecutive patients underwent R-CHOP and 72% achieved a complete remission (CR); 20% suffered a relapse and 31% died. 5-Year progression-free survival (PFS) and overall survival (OS) were 56% and 69%, respectively. We identified several parameters influencing PFS and OS significantly in univariate analysis, but only stage III/IV and hemoglobin <13 g/dl were independent prognosticators for PFS and age >60 years for OS. In comparison to the CHOP(-like)-treated group, the CR rate was similar, while the percentage of relapse was nearly twice in the historical cohort, namely 44%. This translated into a dramatically improved PFS and OS for the R-CHOP group. In conclusion, in a real-life setting R-CHOP results in high percentages of response and long-term remission. Moreover we showed that in the rituximab era, factors other than the single parameters of the international prognostic index significantly influence PFS and OS. Finally, we confirm the independent impact of rituximab on the outcome of an unselected population with DLBCL.