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      Treatment of mantle cell lymphoma in Asia: a consensus paper from the Asian Lymphoma Study Group

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          Abstract

          Background

          Mantle cell lymphoma (MCL) is a B cell malignancy that can be aggressive and with a poor prognosis; the clinical course is heterogeneous. The epidemiology of MCL in Asia is not well documented but appears to comprise 2–6% of all lymphoma cases based on available data, with variation observed between countries. Although international guidelines are available for the treatment of MCL, there is a lack of published data or guidance on the clinical characteristics and management of MCL in patient populations from Asia. This paper aims to review the available treatment and, where clinical gaps exist, provide expert consensus from the Asian Lymphoma Study Group (ALSG) on appropriate MCL management in Asia.

          Body

          Management strategies for MCL are patient- and disease stage-specific and aim to achieve balance between efficacy outcomes and toxicity. For asymptomatic patients with clearly indolent disease, observation may be an appropriate strategy. For stage I/II disease, following international guidelines is appropriate, which include either a short course of conventional chemotherapy followed by consolidated radiotherapy, less aggressive chemotherapy regimens, or a combination of these approaches. For advanced disease, the approach is based on the age and fitness of the patient. For young, fit patients, the current practice for induction therapy differs across Asia, with cytarabine having an important role in this setting. Hematopoietic stem cell transplantation (HSCT) may be justified in selected patients because of the high relapse risk. In elderly patients, specific chemoimmunotherapy regimens available in each country/region are a treatment option. For maintenance therapy after first-line treatment, the choice of approach should be individualized, with cost being an important consideration within Asia. For relapsed/refractory disease, ibrutinib should be considered as well as other follow-on compounds, if available.

          Conclusion

          Asian patient-specific data for the treatment of MCL are lacking, and the availability of treatment options differs between country/region within Asia. Therefore, there is no clear one-size-fits-all approach and further investigation on the most appropriate sequence of treatment that should be considered for this heterogeneous disease.

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          Most cited references72

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          Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study.

          Mantle-cell lymphoma is an aggressive B-cell lymphoma with a poor prognosis. Both ibrutinib and temsirolimus have shown single-agent activity in patients with relapsed or refractory mantle-cell lymphoma. We undertook a phase 3 study to assess the efficacy and safety of ibrutinib versus temsirolimus in relapsed or refractory mantle-cell lymphoma.
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            Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.

            Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.
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              Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma.

              Mantle-cell lymphoma is generally incurable. Despite high rates of complete response after initial immunochemotherapy followed by autologous stem-cell transplantation, patients have relapses. We investigated whether rituximab maintenance therapy at a dose of 375 mg per square meter of body-surface area administered every 2 months for 3 years after transplantation would prolong the duration of response.
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                Author and article information

                Contributors
                wskimsmc@gmail.com
                Journal
                J Hematol Oncol
                J Hematol Oncol
                Journal of Hematology & Oncology
                BioMed Central (London )
                1756-8722
                17 March 2020
                17 March 2020
                2020
                : 13
                : 21
                Affiliations
                [1 ]GRID grid.267370.7, ISNI 0000 0004 0533 4667, Asan Medical Center, , University of Ulsan College of Medicine, ; Seoul, South Korea
                [2 ]GRID grid.452404.3, ISNI 0000 0004 1808 0942, Fudan University Shanghai Cancer Center, ; Shanghai, China
                [3 ]GRID grid.412040.3, ISNI 0000 0004 0639 0054, National Cheng Kung University Hospital, ; Tainan, Taiwan
                [4 ]GRID grid.272242.3, ISNI 0000 0001 2168 5385, National Cancer Center Hospital, ; Tokyo, Japan
                [5 ]GRID grid.264381.a, ISNI 0000 0001 2181 989X, School of Medicine, , Sungkyunkwan University, ; Samsung Medical Center 115 Irown-Ro, Gangnam-Gu, Seoul, South Korea
                [6 ]GRID grid.415550.0, ISNI 0000 0004 1764 4144, Queen Mary Hospital, ; Pok Fu Lam, Hong Kong
                [7 ]GRID grid.488530.2, ISNI 0000 0004 1803 6191, Sun Yat-sen University Cancer Center, ; Guangzhou, China
                [8 ]GRID grid.410724.4, ISNI 0000 0004 0620 9745, National Cancer Center, ; Singapore, Singapore
                [9 ]GRID grid.12955.3a, ISNI 0000 0001 2264 7233, Hospital of Xiamen University, ; Xiamen, China
                [10 ]GRID grid.411602.0, ISNI 0000 0004 0647 9534, Chonnam National University Hwasun Hospital, ; Hwasun, South Korea
                Article
                855
                10.1186/s13045-020-00855-9
                7079508
                32183871
                4b7e77f0-db0e-47cf-a991-4fb06ed64437
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 4 December 2019
                : 3 March 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100008897, Janssen Pharmaceuticals;
                Categories
                Review
                Custom metadata
                © The Author(s) 2020

                Oncology & Radiotherapy
                mantle cell lymphoma,asia,treatment,guidelines
                Oncology & Radiotherapy
                mantle cell lymphoma, asia, treatment, guidelines

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