Ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma: extended 3.5-year follow up from a pooled analysis

Rule, Simon; Dreyling, Martin; Goy, André; Heß, Georg; Auer, Rebecca; Kahl, Brad S.; Hernández‐Rivas, José Ángel; Qi, Keqin; Deshpande, Sanjay; Parisi, Lori; Wang, Michael

doi:10.3324/haematol.2018.205229

Cited by 134 publications

(141 citation statements)

References 13 publications

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“…Development of BTK inhibitors (ibrutinib, acalabrutinib, and zanubritinib) and Bcl‐2 antagonist (venetoclax) has revolutionized our treatment options for relapsed MCL. Remarkable efficacy, durable responses, tolerability, and safety from ibrutinib or acalabrutinib or a combination of ibrutinib with venetoclax in various age groups and disease subsets of MCL has completely overshadowed results from older agents, such as chemotherapy regimens BR (ORR 82%, 40% CR), R‐CHOP or other salvage regimen such as R‐HCVA/methotrexate‐ara‐C (ORR 93%, 45% CR), R‐ICE or R‐DHAP.…”

Section: Advances In the Treatment Of MCLmentioning

confidence: 99%

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Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

2019

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Unprecedented advances in our understanding of the pathobiology, prognostication, and therapeutic options in mantle cell lymphoma (MCL) have taken place in the last few years. Heterogeneity in the clinical course of MCL—indolent vs aggressive—is further delineated by a correlation with the mutational status of the variable region of immunoglobulin heavy chain, methylation status, and SOX‐11 expression. Cyclin‐D1 negative MCL, in situ MCL neoplasia, and impact of the karyotype on prognosis are distinguished. Apart from Ki‐67% and morphology pattern (classic vs blastoid/pleomorphic), the proliferation gene signature has helped to further refine prognostication. Studies focusing on mutational dynamics and clonal evolution on Bruton's tyrosine kinase (BTK) inhibitors (ibrutinib, acalabrutinib) and/or Bcl2 antagonists (venetoclax) have further clarified the prognostic impact of somatic mutations in TP53, BIRC3, CDKN2A, MAP3K14, NOTCH2, NSD2, and SMARCA4 genes. In therapy, long‐term follow‐up on chemo‐immunotherapy studies has demonstrated durable remissions in some patients; however, long‐term toxicities, especially from second cancers, are a serious concern with chemotherapy. The therapeutic options in MCL are constantly evolving, with dramatic responses from nonchemotherapeutic agents (ibrutinib, acalabrutinib, and venetoclax). Chimeric antigen receptor therapy and combinations of nonchemotherapeutic agents are actively being studied and our focus is shifting toward making the treatment of MCL chemotherapy‐free. Still, MCL remains incurable. The following aspects of MCL continue to pose a challenge: disease transformation, role of the cytokine‐microenvironmental milieu, incorporation of positron emission tomography‐computerized tomography imaging, minimal residual disease in the prognosis, circulating tumor DNA testing for clonal evolution, predicting resistance to BTK inhibitors, and optimal management of patients who progress on BTK/Bcl2 inhibitors. Next‐generation clinical trials should incorporate nonchemotherapeutic agents and personalize the treatment based upon the genomic profile of individual patient. Recent advances in the field of MCL are reviewed.

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Section: Advances In the Treatment Of MCLmentioning

confidence: 99%

“…Recently, a pooled analysis of 370 single‐agent‐ibrutinib‐treated relapsed MCL patients with a median of 41.5 months of follow up was reported . Seventeen percent of patients continued to receive treatment for more than 4 years.…”

Section: Advances In the Treatment Of MCLmentioning

confidence: 99%

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

2019

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“…Extrapolating from these data, the decision was made to transition to ibrutinib which has been shown effective and durable in patients with CLL with poor‐risk cytogenetics . Additionally, ibrutinib is also approved for the treatment of mantle cell lymphoma in the relapsed and refractory setting providing further evidence for its potential efficacy in patients with t(11;14) …”

Section: Discussionmentioning

confidence: 99%

Management of atypical chronic lymphocytic leukemia presenting with extreme leukocytosis

Muddasani

Talwar

Suarez-Londono

et al. 2020

Clinical Case Reports

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This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. AbstractAtypical chronic lymphocytic lymphoma (CLL) with CCND1 translocation is poorly described, particularly in the era of modern inhibitors of the B-cell receptor pathway.We present a patient with atypical CLL who had a significant response to ibrutinib, highlighting the effectiveness of this agent in higher risk CLL subgroups. K E Y W O R D SAtypical chronic lymphocytic leukemia, ibrutinib, leukocytosis 878 | MUDDASANI et Al.

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“…However, both response and duration of response are hugely influenced by how early the drug is used in relapse. If used at first relapse, then the response rate is higher at 78% (CR 36%), and the progression free survival is significantly longer than if used at a later line (25.4 v 10.3 months) . The remission duration is dependent on the quality of the remission with a CR lasting around 4 ½ years.…”

Section: Management Of Relapsementioning

confidence: 99%

“…There are two situations where responses to ibrutinib are significantly inferior. In patients with blastoid histology, the progression free survival is only 5 months with only 50% of patients responding and in patients who harbour the TP53 mutation (which is not exclusively in patients with blastoid histology); the progression free survival is only 4 months with a similar response rate . Clearly, alternate approaches are required here.…”

Section: Management Of Relapsementioning

confidence: 99%

The modern approach to mantle cell lymphoma

Rule

2019

Hematological Oncology

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Mantle Cell Lymphoma is a rare and generally aggressive form of non Hodgkin lymphoma. Our understanding of the pathophysiology of this disease is improving and whilst risk factors are understood, treatments are not yet tailored towards these.The treatment algorithm in the front line is well established for older and younger patients and observation is the norm for a subset of patients although these are not well characterised as yet. In the relapse setting the role of novel agents, especially the BTK inhibitors is becoming established and combination approaches look promising. Trials are beginning to challenge the role of chemotherapy against the novel agents especially as part of front line therapy. As a consequence it is likely we will see a paradigm shift in the management of this disease in the next few years.

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Ibrutinib for the treatment of relapsed/refractory mantle cell lymphoma: extended 3.5-year follow up from a pooled analysis

Cited by 134 publications

References 13 publications

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

Mantle cell lymphoma: 2019 update on the diagnosis, pathogenesis, prognostication, and management

Management of atypical chronic lymphocytic leukemia presenting with extreme leukocytosis

The modern approach to mantle cell lymphoma

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