“…For patients with ABC DLBCL, the effective rate of single ibrutinib in relapsed/refractory patients can be as high as 37%, but for patients with GCB DLBCL, the effective rate is only 15%. In terms of combination therapy, the combination of ibrutinib and R-CHOP can significantly improve the efficacy of R/R DLBCL, and the effectiveness of the GCB subtype is still inferior to that of the ABC subtype [ 318 ]. Fig.…”
High-grade B-cell lymphoma with translocations involving MYC and BCL2 or BCL6, usually referred to as double hit lymphoma (DHL), is an aggressive hematological malignance with distinct genetic features and poor clinical prognosis. Current standard chemoimmunotherapy fails to confer satisfying outcomes and few targeted therapeutics are available for the treatment against DHL. Recently, the delineating of the genetic landscape in tumors has provided insight into both biology and targeted therapies. Therefore, it is essential to understand the altered signaling pathways of DHL to develop treatment strategies with better clinical benefits. Herein, we summarized the genetic alterations in the two DHL subtypes (DHL-BCL2 and DHL-BCL6). We further elucidate their implications on cellular processes, including anti-apoptosis, epigenetic regulations, B-cell receptor signaling, and immune escape. Ongoing and potential therapeutic strategies and targeted drugs steered by these alterations were reviewed accordingly. Based on these findings, we also discuss the therapeutic vulnerabilities that coincide with these genetic changes. We believe that the understanding of the DHL studies will provide insight into this disease and capacitate the finding of more effective treatment strategies.
“…For patients with ABC DLBCL, the effective rate of single ibrutinib in relapsed/refractory patients can be as high as 37%, but for patients with GCB DLBCL, the effective rate is only 15%. In terms of combination therapy, the combination of ibrutinib and R-CHOP can significantly improve the efficacy of R/R DLBCL, and the effectiveness of the GCB subtype is still inferior to that of the ABC subtype [ 318 ]. Fig.…”
High-grade B-cell lymphoma with translocations involving MYC and BCL2 or BCL6, usually referred to as double hit lymphoma (DHL), is an aggressive hematological malignance with distinct genetic features and poor clinical prognosis. Current standard chemoimmunotherapy fails to confer satisfying outcomes and few targeted therapeutics are available for the treatment against DHL. Recently, the delineating of the genetic landscape in tumors has provided insight into both biology and targeted therapies. Therefore, it is essential to understand the altered signaling pathways of DHL to develop treatment strategies with better clinical benefits. Herein, we summarized the genetic alterations in the two DHL subtypes (DHL-BCL2 and DHL-BCL6). We further elucidate their implications on cellular processes, including anti-apoptosis, epigenetic regulations, B-cell receptor signaling, and immune escape. Ongoing and potential therapeutic strategies and targeted drugs steered by these alterations were reviewed accordingly. Based on these findings, we also discuss the therapeutic vulnerabilities that coincide with these genetic changes. We believe that the understanding of the DHL studies will provide insight into this disease and capacitate the finding of more effective treatment strategies.
“…Further studies with a larger number of patients with comprehensive molecular subtypes and genomic profile were necessary to analyze their association in between. 19,20 However, there are still limitations in this study. The nomogram we established from this retrospective analysis was only tested with internal validation.…”
Section: Discussionmentioning
confidence: 92%
“…We further analyzed all the histological characteristics that can be retrieved and none of them were related with SCNS involvement. Further studies with a larger number of patients with comprehensive molecular subtypes and genomic profile were necessary to analyze their association in between 19,20 …”
Secondary central nervous system (SCNS) involvement is an infrequent but universally fatal event in diffused large B‐cell lymphoma. The occurrence rate of SCNS involvement is approximately 5% but comes with a poor prognosis ever after. However, existing risk models to predict the incidence and prognosis of these patients with SCNS involvement lack both efficiency and accuracy. Controversy has also been reported regarding which risk factor may best identify the population with a high CNS relapse rate. In this study, we retrospectively analyzed 831 patients with diffused large B‐cell lymphoma, diagnosed between March 2008 and June 2018 in Tianjin Medical University Cancer Institute and Hospital, Beijing Cancer Hospital, and Cancer Hospital of The University of Chinese Academy of Science. Risk factors and nomogram were identified and established based on Fine and Gray's competing risk analysis. Among these patients, 55 (6.6%) of them eventually developed SCNS involvement. The 1‐ and 2‐year incidence for SCNS involvement were 3.9% and 4.7%, respectively. The median time from de novo diagnosis to CNS relapse was 8 months, and the median overall survival of these patients was 28 months. Considering the competing mortality before SCNS involvement, Fine and Gray's competing risk model was performed to analyze the characteristics related to SCNS involvement, and identified risk factors as the multiple extranodal involvements, elevated LDH and AMC level, and the involvement of breast, adrenal gland/kidney, pulmonary and bone. Corresponding factors were integrated into the competing nomogram for SCNS involvement (c‐index = 0.778). In conclusion, we present the first predictive nomogram to evaluate the risk to develop SCNS involvement in de novo DLBCL patients, which may help in both prognostic evaluation and clinical decision for this subgroup.
“…[17][18][19][20] Therefore, the value of the integrative application of CHM as a complementary and alternative intervention for DHL cannot be ignored, given there is currently no accepted standard of therapeutic agents for DHL. 3 However, it should be pointed out that the results from a single case may not apply to patients in general. Further studies are warranted to investigate the efficacy and safety of specific CHM in managing DHL.…”
Section: Discussionmentioning
confidence: 99%
“…2 Double-hit diffuse large B-cell lymphoma, also known as double-hit lymphoma (DHL) occurs in around 5.8% of diffuse large B-cell lymphoma (DLBCL), belonging to NHL. 3 DHL is a high-grade lymphoma characterized by rearrangements in 2 genes, MYC and BCL2 or BCL6. When an anti-apoptotic gene (BCL2 or BCL6) and proliferative gene (MYC) present concurrently, this type of lymphoma becomes more aggressive and poorly responds to the current drug therapies.…”
Double-hit diffuse large B-cell lymphoma (DHL) is an uncommon subtype of lymphoma which poorly responds to current drug therapies and has low rates of long-term survival in the patients. Herein, we report a case of a 73-year-old Caucasian male who was diagnosed with DHL with double-hit mutations of rearrangement of both c-MYC and BCL2 in November 2013. He commenced the standard R-CHOP-14 chemotherapy (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone) but changed to dose-adjusted DA-EPOCH-R protocol (etoposide, doxorubicin, vincristine, cyclophosphamide, prednisone, and rituximab) in the second and third cycles due to double-hit mutation. Because of intolerance to the intensive therapy, the patient decided to switch to Chinese medicine intervention. From March 2014 to December 2019, he was prescribed with a classical Chinese herbal formula— Sijunzi Decoction plus Prunella vulgaris based prescriptions. After 2 months of the Chinese herbal medicine intervention, the patient felt his right groin mass disappeared. Imaging follow-up showed no residual masses, and no lymphadenopathy was seen. During the period of Chinese herbal medicine treatment, his adherence and tolerability were well maintained with no adverse events. Imaging surveillances afterward found no evidence of lymphoma recurrence. His regular blood tests indicated that the patient’s blood counts were normal and stable; no hematologic toxicity, hepatoxicity, or nephrotoxicity associated with Chinese herbal medicine were found. Follow-up visits until 2020 found that he had been living and enjoying a good quality of life for over 8 years post-diagnosis. This case study illustrates the potential values of Chinese herbal medicine in DHL treatment, alongside chemo-immunotherapy, and in maintaining long-term survival and satisfactory quality of life for DHL patients. The case report provides clinicians with preliminary evidence of the use of Chinese herbal medicine as a therapeutic strategy in the management of DHL.
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