Lenalidomide Combined With R-CHOP Overcomes Negative Prognostic Impact of Non–Germinal Center B-Cell Phenotype in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Phase II Study

Nowakowski, Grzegorz S.; LaPlant, Betsy; Macon, William R.; Reeder, Craig B.; Foran, James M.; Nelson, Garth D.; Thompson, Carrie A.; Rivera, Candido E.; Inwards, David J.; Micallef, Ivana N.; Johnston, Patrick B.; Porrata, Luis F.; Ansell, Stephen M.; Gascoyne, Randy D.; Habermann, Thomas M.; Witzig, Thomas E.

doi:10.1200/jco.2014.55.5714

Cited by 327 publications

(259 citation statements)

References 31 publications

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“…Early clinical data showed preferential activity in refractory/relapsed ABC vs. GCB DLBCL, with an overall response rate (ORR) of 53% and 9%, respectively [47]. Given these results, two studies adding lenalidomide to R-CHOP in newly diagnosed DLBCL have recently been completed [48,49]. Ibrutinib is an inhibitor of the Bruton Tyrosine Kinase (BTK), an important component of the B-cell receptor (BCR) pathway.…”

Section: Antiviral Therapy In Combination With Ebv Lytic Phase Inductionmentioning

confidence: 99%

EBV‐positive diffuse large B‐cell lymphoma of the elderly: 2016 update on diagnosis, risk‐stratification, and management

et al. 2016

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Epstein–Barr virus (EBV)‐positive diffuse large B‐cell lymphoma (DLBCL) of the elderly is a provisional entity included in the 2008 WHO classification of lymphoid neoplasms. It is a disease typically seen in the elderly and thought to be associated with chronic EBV infection and severe immunosuppression with a component of immunosenescence. Recent research, however, has suggested that EBV‐positive DLBCL can be seen in younger, immunocompetent patients.The diagnosis of EBV‐positive DLBCL of the elderly is made through a careful pathological evaluation. The differential diagnosis includes infectious mononucleosis (specifically in younger patients), lymphomatoid granulomatosis, Hodgkin lymphoma, and gray zone lymphoma, among others. Detection of EBV‐encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined.The International Prognostic Index (IPI), and the Oyama score can be used for risk‐stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 is emerging as a potential adverse, and targetable, prognostic factor.Patients with EBV‐positive DLBCL should be staged and managed following similar guidelines than patients with EBV‐negative DLBCL. It has been suggested, however, that EBV‐positive patients have a worse prognosis than EBV‐negative counterparts in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV‐positive DLBCL. Am. J. Hematol. 91:530–537, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Antiviral Therapy In Combination With Ebv Lytic Phase Inductionmentioning

confidence: 99%

EBV‐positive diffuse large B‐cell lymphoma of the elderly: 2016 update on diagnosis, risk‐stratification, and management

et al. 2016

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“…Az R 2 -CHOP (R-CHOP + lenalidomid 25 mg) alkalmazásával az ABC-csoportban a 2 éves túlélés 46%-ról 83%-ra nőtt. Ez a különbség nem látható a GCB-csoportban [42]. Ezen adatok alapján az ABC-altípus kezelésében a lenalidomid alkalmazása mindenkép-pen szóba jön.…”

Section: A Dlbcl Kezelése Maunclassified

A diffúz nagy B-sejtes lymphoma modern szemlélete és kezelése

Gergely

Illés

2016

Orvosi Hetilap

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A diffúz nagy B-sejtes lymphoma a leggyakoribb a non-Hodgkin-lymphomák között. A ciklofoszfamid-vincristinadriablastin-prednisolon kemoterápiával a betegeknek már közel 50%-a meggyógyítható volt, majd a rituximab hozzáadásával a gyógyulási arány már 60% fölé emelkedett. Ez a javulás jelentős, de további növekedést kellene elérni a betegek gyógyulási arányában. Az utóbbi években elvégzett genetikai vizsgálatok számos új, a patogenezisben is szerepet játszó és terápiás célpontként is szolgáló mutációt azonosítottak a betegségben. A diagnosztika ma már rutinszerűen alkalmazza a 18-fluoro-deoxi-glükóz-pozitronemissziós komputertomográfiás vizsgálatokat a Lugano klasszifikációs rendszer részeként. Ezen adatok alapján egyre pontosabban meghatározható a betegek prognózisa, és kiválaszthatók azok a betegek, akik valamelyik új, szelektíven ható gyógyszerre esetleg reagálhatnak. Mindezeknek a kérdéseknek a megválaszolása, az újabb kezelések bevezetése várhatóan a közeli jövőben tovább fogja javítani a betegek túlélési esélyeit. Az összefoglaló közlemény áttekintést ad a közelmúlt újdonságairól, kiemeli a ma használatos és javasolt kezeléseket, továbbá áttekintést ad a jelenleg kipróbálás alatt álló és bevezetendő kezelésekről is. Orv. Hetil., 2016, 157(31), 1232-1241. Kulcsszavak: lymphoma, DLBCL, kezelés Recent advances in the understanding and treatment of diffuse large B-cell lymphomaDiffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. Using the conventional cyclophosphamide adriablastin vincristin prednisolon polychemotherapy about 50% of the patients were cured. The addition of rituximab to the regimen increased the cure rate to 60%. This is a major improvement, however, further advance is still needed to increase the cure rate. The extensive genetic testing performed recently revealed several important pathognomic mutations as potential targets in this disease. Routine diagnosis of patients now includes the use of 18 Fluor-deoxy-glucose positron emission computer tomography, according to the recent Lugano classification system. With all these data we can better predict the prognosis of patients, and we can select candidates for novel targeted therapies as well. Answering these questions, and utilizing novel therapies possibly will further increase the cure rate in the near future. This paper summarizes current diagnostic and therapeutic approaches and describes recent understanding in the mutations and pathognomic changes resulting in the disease. The authors also summarize the data available on experimental therapies possibly entering clinical pratice in the forthcoming years. Keywords: lymphoma, DLBCL, treatmentGergely, L., Illés, Á. [Recent advances in the understanding and treatment of diffuse large B-cell lymphoma]. Orv. Hetil., 2016, 157(31), 1232-1241. (Beérkezett: 2016 elfogadva: 2016. május Rövidítések 18 FDG = 18-fluoro-deoxi-glükóz; ABC = aktivált B-sejtes; ADCC = antitest-közvetített sejt mediálta citotoxicitás; antiHBc = hepatitis B-vírus-mag-antigén elleni ellenanyag; ...

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“…The British Columbia Cancer Agency (BCCA) and colleagues reported that the non-GCB and GCB subtypes had a similar outcome in stage II-IV DLBCL treated with 6 cycles of R2-CHOP. 30 The Fondazione Italiana Linfomi group also reported that there was no difference in 2-year PFS (81% vs. 71%; p = 0.705) and OS (94% vs. 88%; p = 0.58) in patients with stage II-IV disease, 60-80 years of age, treated with 6 cycles of R2-CHOP between the non-GCB type and GCB type, with a median follow-up in survivors of 28 mon (REAL07). 31 Several clinical trials, such as phase III trials comparing R-CHOP and R2CHOP and trials consisting of lenalidomide maintenance therapy, have been conducted on untreated DLBCL.…”

Section: Immunomodulatory Drugsmentioning

confidence: 99%

Treatment of Diffuse Large B-Cell Lymphoma

Miyazaki

2016

JCEH

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Diffuse large B-cell lymphoma (DLBCL) comprises a heterogeneous group with pathophysiological, genetic and clinical features. Many patients can be cured with R-CHOP therapy, which is the current standard regimen. Despite recent progress in improving patient survival, the 40% survival of DLBCL patients remains poor. Therefore, the most important issue for patients with DLBCL remains the development of a new front-line therapy. Several studies have reported that intensified chemotherapy with dose-adjusted EPOCH-R or R-ACVBP was superior to R-CHOP. Gene expression profiling has identified two distinct forms of DLBCL: activated B cell-like (ABC) and germinal center B-cell-like (GCB) types. ABC DLBCL exhibits a worse prognosis than GCB DLBCL by molecular diagnosis after R-CHOP therapy. Next-generation sequencing has identified unique oncogenic mechanisms and genetic complexity, which has provided rational therapeutic targets. There are also a number of biomarkers, including CD5, and prognostic factors. Efforts to distinguish many biomarkers will be crucial for individualized treatment in the future. 〔J Clin Exp Hematop 56(2):79-88, 2016〕

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Lenalidomide Combined With R-CHOP Overcomes Negative Prognostic Impact of Non–Germinal Center B-Cell Phenotype in Newly Diagnosed Diffuse Large B-Cell Lymphoma: A Phase II Study

Abstract: R2CHOP shows promising efficacy in DLBCL. The addition of lenalidomide appears to mitigate a negative impact of non-GCB phenotype on patient outcome.

Cited by 327 publications

References 31 publications

EBV‐positive diffuse large B‐cell lymphoma of the elderly: 2016 update on diagnosis, risk‐stratification, and management

EBV‐positive diffuse large B‐cell lymphoma of the elderly: 2016 update on diagnosis, risk‐stratification, and management

A diffúz nagy B-sejtes lymphoma modern szemlélete és kezelése

Treatment of Diffuse Large B-Cell Lymphoma

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