First‐line treatment of double‐hit and triple‐hit lymphomas: Survival and tolerance data from a retrospective multicenter French study

Laude, Marie-Charlotte; Lebras, Laure; Sesques, Pierre; Ghesquières, Hervé; Favre, Simon; Bouabdallah, Krimo; Croizier, Carolyne; Guièze, Romain; Rochelle, Laurianne Drieu La; Gyan, Emmanuel; Chin, R; Aurran-Schleinitz, Thérèse; Marouf, Amira; Deau‐Fischer, Bénédicte; Coppo, Paul; Malot, Sandrine; Roussel, Xavier; Chauchet, Adrien; Schwarz, Marianne; Bescond, Charles; Chapelle, Thierry; Bussot, Lucile; Carras, Sylvain; Burlet, Bénédicte; Rossi, Cédric; Daniel, Adrien; Morschhauser, Franck; Subtil, Fabien; Michallet, Anne‐Sophie

doi:10.1002/ajh.26068

Cited by 40 publications

(36 citation statements)

References 24 publications

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“…Similar results were obtained by independent studies in 2014( n = 129),2017(two studies, n 1 = 159, n 2 = 117) and 2021( n = 160). Auto-SCT after a front line or intensive chemotherapy in DHL patients did not affect 3-year PFS or OS after first CR [ 13 , 33 , 36 , 39 ]. On the other hand, these studies again emphasize the importance of intensive therapy compared to front-line therapy in improving the 3-year RFS [ 36 ].…”

Section: Diagnosis Prognosis and Current Treatmentmentioning

confidence: 99%

Altered pathways and targeted therapy in double hit lymphoma

Zhuang

Che

et al. 2022

J Hematol Oncol

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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.

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Section: Diagnosis Prognosis and Current Treatmentmentioning

confidence: 99%

Altered pathways and targeted therapy in double hit lymphoma

Zhuang

Che

et al. 2022

J Hematol Oncol

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“…Interestingly, the CR rates between the two groups were not substantially different. A previous study revealed that DH DLBCL might bene t more from intensi ed chemotherapy [30]. Therefore, we examined the disease course of each DH DLBCL in our study cohort.…”

Section: Clinical Data Of Dh (+) Dlbcl Patientsmentioning

confidence: 99%

Clinical features and immunophenotypes of double-hit diffuse large B-cell lymphoma

Teng

Shih

et al. 2022

Preprint

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Double-hit (DH) genetics induces a reduction in the complete remission (CR) and, consequently, in poor overall survival (OS) in diffuse large B-cell lymphoma (DLBCL) patients. Unfortunately, DH identification is time-consuming. Here, we retrospectively reviewed 92 newly diagnosed DLBCL patients and stratified them into the DH (n = 14) and non-DH groups (n = 78). The clinical features and treatment outcomes were compared between the two groups, and clinical parameters were employed to predict DH genetics. The results revealed that the DH group had a higher percentage of bulky disease than the non-DH group (64.3% vs. 28.2%; p = 0.013). More patients in the DH group tested positive for double expresser (DE) (50.0% vs. 21.8%; p = 0.044). Conversely, the CR rates in these groups were not significantly different (50.0% vs. 60.3%; p = 0.672). The three-year OS rates of patients with and without DH were 28.6% and 49.7%, respectively (p = 0.008). Importantly, DH genetics (HR: 6.19; 95% CI: 1.59–24.07; p = 0.009), advance stage (HR: 9.24; 95% CI: 1.34–63.63; p = 0.024), and a high uric acid level (HR: 1.24; 95% CI: 1.00–1.54; p = 0.046) were correlated with a high mortality rate. Furthermore, by combining DE and the bulky disease, a specificity of 89.7% for DH prediction was achieved. In summary, DH genetics, not DE immunopositivity, is a poor prognostic factor for newly diagnosed DLBCL. A combination of bulky disease and a positive DE immunophenotype could facilitate DH genetics prediction in newly diagnosed DLBCL patients.

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“…Also, a large, recently published French ret ro spec tive study eval u ated 160 patients with HGBL (with MYC and BCL2 and/or BCL6) and dem on strated a sig nifi cantly lon ger PFS for inten sive ther apy vs R-CHOP. 18 HGBL-NOS cases are much rarer, and hence, there are a pau city of data to inform on opti mal treat ment.…”

Section: Approach To Hgbl With Myc and Bcl2 And/or Bcl6 Rearrangementsmentioning

confidence: 99%

Double-hit lymphoma: optimizing therapy

Dunleavy

2021

Hematology

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Aggressive B-cell lymphoma is a heterogeneous entity with disparate outcomes based on clinical and pathological characteristics. While most tumors in this category are diffuse large B-cell lymphoma (DLBCL), the recognition that some cases have high-grade morphology and frequently harbor MYC and BCL2 and/or BCL6 translocations has led to their separate categorization. These cases are now considered distinct from DLBCL and are named “high-grade B-cell lymphoma” (HGBL). Most are characterized by distinct rearrangements, but others have high-grade morphological features without these and are called HGBL-not otherwise specified. Studies have demonstrated that this group of diseases leads to poor outcomes following standard rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone therapy; retrospective and recent single-arm, multicenter studies suggest they should be approached with dose-intense treatment platforms. As yet, this has not been validated in randomized trial settings due to the rarity of these diseases. In the relapsed and refractory setting, novel approaches such as anti-CD19 chimeric antigen receptor T cells and antibodies against CD19 have demonstrated high efficacy in this subgroup. Recently, genomic studies have made much progress in investigating some of the molecular underpinnings that drive their lymphomagenesis and have paved the way for testing additional novel approaches.

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First‐line treatment of double‐hit and triple‐hit lymphomas: Survival and tolerance data from a retrospective multicenter French study

Cited by 40 publications

References 24 publications

Altered pathways and targeted therapy in double hit lymphoma

Altered pathways and targeted therapy in double hit lymphoma

Clinical features and immunophenotypes of double-hit diffuse large B-cell lymphoma

Double-hit lymphoma: optimizing therapy

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