Mantle cell lymphoma strategies in primary treatment

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Mantle cell lymphoma (MCL) is associated with poor prognosis due to an aggressive clinical course. Being a rare disease, there are few randomized trials in MCL and there is no defined golden standard in primary treatment.

This works aimed to (I) investigate outcome in relation to primary treatment in MCL based on population-based registry data, (II) to evaluate tolerability and efficacy of lenalidomide-rituximab-bendamustine (LBR) in newly diagnosed MCL patients within a phase I/II trial (MCL4) including (III) outcome in relation to genetic alterations, and (IV) to study how novel agents interfere with response to anti-CD20 antibodies.

Our results showed that survival in MCL patients improved during 2000-2011, which partly could be explained by the introduction of rituximab and intensified treatment with high dose chemotherapy consolidation. We also found that treatment with radiotherapy to limited-stage disease and observation in non-symptomatic MCL were associated with long-term survival. In paper II and III, LBR was found to be an active combination in untreated MCL patients, except for cases harboring TP53 mutations, but associated with significant toxicity including second primary malignancies. In paper IV, we showed that the BTK-inhibitor ibrutinib, negatively affected the immune mediated cell death induced by a type I or II anti-CD20 antibody in MCL cell lines, not restored by addition of lenalidomide, a potential sensitizer to anti-CD20 ab.

This work has provided data on important factors for outcome in MCL that may be taken into clinical use, such as active observation in non-symptomatic patients and rituximab and intensified approaches in primary treatment. Moreover, the addition of lenalidomide to BR could not be recommended as first-line treatment in MCL due to excessive toxicity and novel combinations with activity in elderly patients as well as in TP53 mutated MCL are highly warranted. Future studies, including in vitro models on drug interaction will clarify how novel agents should be combined for optimal use in MCL.

Details

Authors
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • mantle cell lymphoma, real-world data, lenalidomide, rituximab, bendamustin, ibrutinib, ADCC, TP53 mutation, CDKN2A, NGS, MIPI, Watchful waiting
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
Award date2018 Apr 19
Place of PublicationLund
Publisher
  • Lund University: Faculty of Medicine
Print ISBNs978-91-7619-595-6
Publication statusPublished - 2018
Publication categoryResearch

Bibliographic note

Defence details Date: 2018-04-19 Time: 09:00 Place: Föreläsningssalen, Onkologikliniken, Universitetssjukhuset i Lund External reviewer(s) Name: Kluin-Nelemans, Hanneke Title: professor Affiliation: University of Groningen, Netherlands --- ISSN: 1652-8220 Lund University, Faculty of Medicine Doctoral Dissertation Series 2018:28

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Research output: Contribution to journalArticle

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Research output: Contribution to journalArticle

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