Mantle cell lymphoma strategies in primary treatment
(2018) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2018(28).- 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... (More) - 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.
(Less) - Abstract (Swedish)
- 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... (More) - 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/efd53312-9b59-4e37-99b5-e97ff8591faa
- author
- Albertsson Lindblad, Alexandra LU
- supervisor
-
- Mats Jerkeman LU
- Sara Ek LU
- opponent
-
- professor Kluin-Nelemans, Hanneke, University of Groningen, Netherlands
- organization
- alternative title
- Mantelcellslymfom : strategier i primärbehandling
- publishing date
- 2018
- type
- Thesis
- publication status
- published
- subject
- keywords
- mantle cell lymphoma, registry data, Clinical Trial, Phase I, Clinical Trial, Phase II, rituximab, bendamustine, lenalidomid, ibrutinib, ADCC, in vitro model, TP53 mutations, watchful waiting, mantle cell lymphoma, real-world data, lenalidomide, rituximab, bendamustin, ibrutinib, ADCC, TP53 mutation, CDKN2A, NGS, MIPI, Watchful waiting
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series
- volume
- 2018
- issue
- 28
- pages
- 130 pages
- publisher
- Lund University: Faculty of Medicine
- defense location
- Föreläsningssalen, Onkologikliniken, Universitetssjukhuset i Lund
- defense date
- 2018-04-19 09:00:00
- ISSN
- 1652-8220
- ISBN
- 978-91-7619-595-6
- language
- English
- LU publication?
- yes
- additional info
- ISSN: 1652-8220 Lund University, Faculty of Medicine Doctoral Dissertation Series 2018:28
- id
- efd53312-9b59-4e37-99b5-e97ff8591faa
- date added to LUP
- 2018-03-22 09:21:43
- date last changed
- 2019-11-19 13:49:34
@phdthesis{efd53312-9b59-4e37-99b5-e97ff8591faa,
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. <br/><br/>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. <br/><br/>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. <br/><br/>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. <br/>}},
author = {{Albertsson Lindblad, Alexandra}},
isbn = {{978-91-7619-595-6}},
issn = {{1652-8220}},
keywords = {{mantle cell lymphoma; registry data; Clinical Trial, Phase I; Clinical Trial, Phase II; rituximab; bendamustine; lenalidomid; ibrutinib; ADCC; in vitro model; TP53 mutations; watchful waiting; mantle cell lymphoma; real-world data; lenalidomide; rituximab; bendamustin; ibrutinib; ADCC; TP53 mutation; CDKN2A; NGS; MIPI; Watchful waiting}},
language = {{eng}},
number = {{28}},
publisher = {{Lund University: Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series}},
title = {{Mantle cell lymphoma strategies in primary treatment}},
url = {{https://lup.lub.lu.se/search/files/42063963/Mantle_cell_lymphoma_strategies_in_primary_treatment_thesis_for_Lucris247510_2_G5_Alexandra_A.pdf}},
volume = {{2018}},
year = {{2018}},
}