Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial

Glaß, Bertram; Dohm, Andrea; Truemper, Lorenz; Pfreundschuh, Michael; Bleckmann, Annalen; Wulf, Gerald; Rosenwald, Andreas; Ziepert, Marita; Schmitz, Norbert

doi:10.1093/annonc/mdx556

Cited by 13 publications

(13 citation statements)

References 20 publications

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“…Hamadani et al reported that patients with an early relapse had shorter OS than patients with a primary refractory disease who were treated with ASCT (2‐year OS 59% vs 41%). By contrast, 3 recent reports showed that patients with an early relapse had better OS than patients with a primary refractory disease . In our report, these 2 subgroups of refractory patients had comparable outcomes.…”

Section: Discussioncontrasting

confidence: 70%

“…Our reported difference in OS between these 2 groups of patients is consistent with the data available in the literature (Table ). The 2‐year OS of primary refractory patients ranged from 10% to 30% in the literature, and this variation in OS score is likely dependent on the definition of refractoriness (progressive vs stable disease), the age of the patient, and the patient's eligibility for ASCT . Hamadani et al reported that patients with an early relapse had shorter OS than patients with a primary refractory disease who were treated with ASCT (2‐year OS 59% vs 41%).…”

Section: Discussionmentioning

confidence: 99%

“…The second conclusion is that retreatment with rituximab is beneficial in a multivariate analysis, independently from age and aaIPI score, as well as chemo regimen. Although the benefit of rituximab in addition to chemo has been studied by other investigators, the value of rituximab in this specific population that was refractory to an initial immunochemotherapy regimen has not been reported to date. The benefit of an intensive platinum‐based salvage regimen is less clear after adjustment for aaIPI score and rituximab use.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Refractory diffuse large B‐cell lymphoma after first‐line immuno‐CT: Treatment options and outcomes

Filliatre-Clement

Maucort‐Boulch

Bourbon

et al. 2018

Hematological Oncology

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In the rituximab era, one-third of diffuse large B-cell lymphoma patients experience relapse/refractory disease after first-line anthracycline-based immunochemotherapy. Optimal management remains an unmet medical need. The aim of this study was to report the outcomes of a cohort of refractory patients according to their patterns of refractoriness and the type of salvage option. We performed a retrospective analysis, which included 104 diffuse large B-cell lymphoma patients treated at Lyon Sud University Hospital (2002-2017) who presented with refractory disease. Refractoriness was defined as progressive/stable disease during first-line treatment (primary refractory, N = 47), a partial response after the end of first-line treatment that required subsequent treatment (residual disease, N = 19), or relapse within 1 year of diagnosis after an initial complete response (CR) (early relapse, N = 38). The 2-year overall survival (OS) rates for primary refractory, early relapse, and residual disease patients were 27%, 25%, and 52%, respectively, while the event-free survival rates for those groups were 13%, 13%, and 42%, respectively. In a univariate analysis, lactate dehydrogenase level, Ann Arbor stage, poor performance status, high age-adjusted International Prognostic Index score, and age > 65 years were associated with shorter OS. The use of rituximab and platinum-based chemo during the first salvage treatment was associated with prolonged OS. In a multivariate analysis, age (HR:2.06) and rituximab use (HR:0.54) were associated with OS. Among patients <65 years who achieved a CR, autologous stem-cell transplant was associated with higher 2-year OS (90% vs 74%, P = 0.10). Patients who were treated with a targeted therapy in the context of a clinical trial after second-line treatment had a higher 2-year OS (34% vs 19%, P = 0.06). In conclusion, patients with primary refractory disease or early relapse have very poor outcomes but may benefit from rituximab retreatment during the first salvage treatment.

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Section: Discussioncontrasting

confidence: 70%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Refractory diffuse large B‐cell lymphoma after first‐line immuno‐CT: Treatment options and outcomes

Filliatre-Clement

Maucort‐Boulch

Bourbon

et al. 2018

Hematological Oncology

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“…management of these patients remains challenging [23][24][25][26][27]. The information provided in this cohort of patients with NHL, the largest reported to date, is useful and relevant, especially in the era of evolving therapies.…”

mentioning

confidence: 96%

The Impact of Advanced Patient Age on Mortality after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma: A Retrospective Study by the European Society for Blood and Marrow Transplantation Lymphoma Working Party

Kyriakou

Boumendil

Finel

et al. 2019

Biology of Blood and Marrow Transplantation

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More than 60% of patients with non-Hodgkin lymphoma (NHL) are age >60 years at presentation. The purpose of this study was to compare the potential risks and benefits of allogeneic hematopoietic cell transplantation (alloHCT) in elderly patients with NHL with younger patients in a large sample, also taking into account comorbidity information. All patients age ≥18 years who had undergone alloHCT from a matched sibling or unrelated donor for NHL between 2003 and 2013 and were registered with the European Society for Blood and Marrow Transplantation were eligible for the study. The primary study endpoint was 1-year nonrelapse mortality (NRM). A total of 3919 patients were eligible and were categorized by age: young (Y), 18 to 50 y (n = 1772); middle age (MA), 51 to 65 y (n = 1967); or old (O), 66 to 77 y (n = 180). Follicular lymphoma was present in 37% of the patients; diffuse large B cell lymphoma, in 30%; mantle cell lymphoma, in 21%, and peripheral T cell lymphoma, in 11%. At the time of alloHCT, 85% of the patients were chemosensitive and 15% were chemorefractory. With a median follow-up of 4.5 years in survivors, NRM at 1 year was 13% for the Y group. 20% for the MA group, and 33% for the O group (P <.001), whereas relapse incidence and overall survival (OS) at 3 years in the 3 groups were 30%, 31%, and 28% (P = .355) and 60%, 54%, and 38% (P <.001), respectively. Multivariable adjustment for confounders, including sex, NHL subset, time from diagnosis, chemosensitivity, donor, and conditioning, confirmed older age as a significant predictor for NRM and OS, but not for relapse risk. Although comorbidity was a significant predictor of NRM in a subset analysis restricted to the 979 patients with comorbidity information available, age retained its significant impact on NRM. In conclusion, our data show that alloHCT in patients age >65 y provides similar NHL control as seen in younger patients but is associated with a higher NRM that is not fully explained by comorbidity. Thus, although alloHCT is feasible and effective in very old patients, the increased NRM risk must be taken into account when assessing the indication for alloHCT for NHL in this age group.

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“…Für ältere Patienten ohne Möglichkeit einer Hochdosistherapie war die Prognose in der Regel bisher schlecht, da keine kurativen Therapieoptionen angeboten werden konnten [12]. Das Therapieprinzip der chimären Antigenrezeptor-T-Zellen (CAR-T-Zellen) führt über die gentechnische Veränderung des T-Zell-Rezeptors zu einer Erkennung und einer konsekutiven Zerstörung von CD19-positiven Lymphomzellen.…”

Section: Behandlung Von Patienten Mit Rezidiviertem Oder Therapierefraktärem Dlbclunclassified

Aktuelle Standards in der Diagnostik und Therapie aggressiver B-Zell-Lymphome

Friedrichs

Schmitz

Lenz

2020

Dtsch med Wochenschr

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Was ist neu? Molekulare Charakterisierung aggressiver Lymphome Die sogenannte „cell of origin“-Klassifikation von diffusen großzelligen B-Zell-Lymphomen (DLBCL) ist mittlerweile Bestandteil der revidierten WHO-Klassifikation von 2017. Dabei werden ABC- und GCB-DLBCL unterschieden. In der Praxis erfolgt diese Einteilung in der Regel unter Anwendung der Immunhistochemie, wobei meist der sogenannte Hans-Algorithmus eingesetzt wird. Erstlinientherapie von DLBCL-Patienten Die Hinzunahme verschiedener zielgerichteter Therapien konnte den Standard von 6–8 Zyklen R-CHOP-Chemoimmunotherapie bislang nicht verändern. Für junge Patienten bis 60 Jahre mit einem International Prognostic Index (IPI) von 0 kann die Therapie auf 4 Zyklen R-CHOP, gefolgt von 2 Applikationen Rituximab, reduziert werden. Prophylaxe von ZNS-Rezidiven bei DLBCL-Patienten Eine intrathekale Therapie mit chemotherapeutischen Substanzen hat keinen Einfluss auf die Verhinderung von Rezidiven im Bereich des zentralen Nervensystems (ZNS). Die Anwendung des ZNS-IPI zur Identifizierung von Patienten mit hohem Risiko für ein ZNS-Rezidiv erscheint sinnvoll, auch wenn es hierzu keine Daten aus randomisierten Studien gibt. Für Patienten mit einem hohen Risiko können 2 systemische Zyklen mit hochdosiertem Methotrexat zusätzlich zur Erstlinientherapie empfohlen werden. Behandlung von Patienten mit rezidiviertem oder therapierefraktärem DLBCL Patienten mit rezidiviertem und/oder refraktärem DLBCL erhalten eine Salvage-Chemotherapie, gefolgt von autologer oder allogener Stammzelltransplantation. Nach mindestens 2 Vortherapien sind aktuell 2 CAR-T-Zell-Produkte zugelassen. Dadurch erhalten auch ältere Patienten, die ggf. nicht für eine Transplantation infrage kommen, die Chance auf eine kurative Therapieoption. Ausblick Neue Substanzgruppen wie Antikörper-Medikamenten-Konjugate oder bispezifische Antikörper zeigen in Studien von Patienten mit rezidiviertem oder therapierefraktärem DLBCL sehr vielversprechende Ergebnisse. Aktuell laufende klinische Studien prüfen den Einsatz weiterer neuer Substanzen.

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Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial

Cited by 13 publications

References 20 publications

Refractory diffuse large B‐cell lymphoma after first‐line immuno‐CT: Treatment options and outcomes

Refractory diffuse large B‐cell lymphoma after first‐line immuno‐CT: Treatment options and outcomes

The Impact of Advanced Patient Age on Mortality after Allogeneic Hematopoietic Cell Transplantation for Non-Hodgkin Lymphoma: A Retrospective Study by the European Society for Blood and Marrow Transplantation Lymphoma Working Party

Aktuelle Standards in der Diagnostik und Therapie aggressiver B-Zell-Lymphome

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