Treatment of patients with MYC rearrangement positive large B-cell lymphoma with R-CHOP plus lenalidomide: results of a multicenter phase II HOVON trial

被引：35

作者：

Chamuleau, Martine E. D. ^{[1
]}

Burggraaff, Coreline N. ^{[1
]}

Nijland, Marcel ^{[2
]}

Bakunina, Katerina ^{[3
]}

Mous, Rogier ^{[4
]}

Lugtenburg, Pieternella J. ^{[5
]}

Dierickx, Daan ^{[6
]}

van Imhoff, Gustaaf W. ^{[2
]}

Vermaat, Joost S. P. ^{[7
]}

Marijt, Eric A. F. ^{[7
]}

Visser, Otto ^{[8
]}

Mandigers, Caroline ^{[9
]}

Bilgin, Yavuz M. ^{[10
]}

Beeker, Aart ^{[11
]}

Durian, Mark F. ^{[12
]}

van Rees, Bas P. ^{[13
]}

Bohmer, Lara H. ^{[14
]}

Tick, Lidwine W. ^{[15
]}

Boersma, Rinske S. ^{[16
]}

Snijders, Tjeerd J. F. ^{[17
]}

Schouten, Harry C. ^{[18
]}

Koene, Harry R. ^{[19
]}

de Jongh, Eva ^{[20
]}

Hijmering, Nathalie ^{[21
,22
]}

Diepstra, Arjan ^{[22
]}

van de Berg, Anke ^{[22
]}

Arens, Anne I. J. ^{[23
]}

Huijbregts, Julia ^{[24
]}

Hoekstra, Otto ^{[25
]}

Zijlstra, Josee M. ^{[1
]}

de Jong, Daphne ^{[21
]}

Kersten, Marie Jose ^{[26
]}

机构：

[1] Vrije Univ Amsterdam, Canc Ctr Amsterdam, Amsterdam UMC, Dept Hematol, Amsterdam, Netherlands

[2] Univ Groningen, Dept Hematol, UMC Groningen, Groningen, Netherlands

[3] Erasmus MC, Dept Hematol, HOVON Data Ctr, Canc Inst, Rotterdam, Netherlands

[4] Univ Med Ctr Utrecht, Dept Hematol, UMC Utrecht Canc Ctr, Utrecht, Netherlands

[5] Erasmus MC, Canc Inst, Dept Hematol, Rotterdam, Netherlands

[6] Univ Hosp Leuven, Dept Hematol, Leuven, Belgium

[7] Leiden Univ, Dept Hematol, Med Ctr, Leiden, Netherlands

[8] Oncol Ctr Isala, Dept Hematol, Zwolle, Netherlands

[9] Canisius Wilhelmina Hosp, Dept Hematol, Nijmegen, Netherlands

[10] Admiraal Ruijter Hosp Goes, Dept Internal Med, Goes, Netherlands

[11] Spaarne Gasthuis, Dept Internal Med, Hoofddorp, Netherlands

[12] Tweesteden Hosp, Dept Internal Med, Tilburg, Netherlands

[13] Tjongerschans Hosp, Dept Internal Med, Heerenveen, Netherlands

[14] Haga Hosp, Dept Internal Med, The Hague, Netherlands

[15] Maxima Med Ctr, Dept Internal Med, Veldhoven, Netherlands

[16] Amphia Hosp, Dept Internal Med, Breda, Netherlands

[17] Med Spectrum Twente, Dept Hematol, Enschede, Netherlands

[18] Maastricht UMC, Dept Hematol, Maastricht, Netherlands

[19] St Antonius Hosp, Dept Internal Med, Nieuwegein, Netherlands

[20] Albert Schweitzer Hosp, Dept Internal Med, Dordrecht, Netherlands

[21] Vrije Univ Amsterdam, Amsterdam UMC, Dept Pathol, Amsterdam, Netherlands

[22] Univ Groningen, UMC Groningen, Dept Pathol & Med Biol, Groningen, Netherlands

[23] Radboud Univ Nijmegen, Dept Radiol & Nucl Med, Med Ctr, Nijmegen, Netherlands

[24] Gelre Hosp, Dept Radiol & Nucl Med, Apeldoorn, Netherlands

[25] Vrije Univ Amsterdam, Amsterdam UMC, Dept Radiol & Nucl Med, Amsterdam, Netherlands

[26] Univ Amsterdam, Canc Ctr Amsterdam, Amsterdam UMC, Dept Hematol, Amsterdam, Netherlands

来源：

HAEMATOLOGICA | 2020年 / 105卷 / 12期

关键词：

DOUBLE-HIT LYMPHOMA; BONE-MARROW INVOLVEMENT; NON-HODGKIN-LYMPHOMA; RESPONSE ASSESSMENT; POOR-PROGNOSIS; FDG PET/CT; SUBTYPES; OUTCOMES;

D O I：

10.3324/haematol.2019.238162

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Patients with MYC-rearrangement positive large B-cell lymphoma (MYC+ LBCL) have an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) compared to patients withoutMYC rearrangement. Although intensive chemotherapy regimens yield higher remission rates, toxicity remains a concern. Lenalidomide is an oral immunomodulatory drug which downregulates MYC and its target genes thereby providing support using lenalidomide as additional therapeutic option for MYC+ LBCL. A phase II trial was conducted evaluating the efficacy of lenalidomide (15 mg day 1-14) in combination with R-CHOP (R2CHOP) in newly diagnosed MYC+ LBCL patients identified through a nationwide MYCFISH screening program. The primary endpoint was complete metabolic response (CMR) on centrally reviewed F-18-fluorodeoxyglucose (F-18-FDG) positron emission tomography (PET)-computer tomography (CT)-scan at end-of-treatment. Secondary endpoints were overall survival (OS), disease free survival (DFS) and event-free survival (EFS). Eighty-two patients with stage II-IV MYC+ LBCL were treated with six cycles of R2CHOP. At end of treatment, 67% (95% Confidence interval [CI]: 58-75) of the patients reached CMR. With a median follow-up of 25.4 months, 2-year estimates for OS, DFS, EFS were 73% (95% CI: 62-82), 75% (95% CI: 63-84) and 63% change to: (95% CI: 52-73) respectively. In this prospective trial for newly diagnosed MYC+ LBCL patients, we found that administering R2CHOP was safe, and yields comparable CMR and survival rates as in studies applying more intensive chemotherapy regimens. Hence, these findings offer new prospects for MYC+ LBCL patients and warrant comparison in prospective randomized clinical trials. This trial was registered at www.clinicaltrialsregister.eu (#2014-002654-39).

引用

页码：2805 / 2812

页数：8

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