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15 results on '"Bohmer, Lara H."'

1. Impact of comorbidity on health-related quality of life in newly diagnosed patients with lymphoma or multiple myeloma: results from the PROFILES-registry

Author

Ekels, Afke, van de Poll-Franse, Lonneke V., Issa, Djamila E., Hoogendoorn, Mels, Nijziel, Marten R., Koster, Adrianus, de Jong, Cornelis N., Achouiti, Ahmed, Thielen, Noortje, Tick, Lidwine W., te Boome, Liane C. J., Bohmer, Lara H., Tiren-Verbeet, Nicolette L., Veldhuis, Gerrit J., de Boer, Fransien, van der Klift, Marjolein, Posthuma, Eduardus F. M., and Oerlemans, Simone

Published
2024
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2. Clinical characteristics and survival outcomes of patients with primary central nervous system lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies

Author

de Groot, Fleur A., Dekker, Tim J.A., Doorduijn, Jeanette K., Böhringer, Stefan, Brink, Mirian, de Groen, Ruben A.L., de Haan, Lorraine M., Woei-A-Jin, F.J. Sherida H., Noordenbos, Troy, Sijs-Szabo, Aniko, Oudshoorn, Mirjam A., Lam, King H., Diepstra, Arjan, te Boome, Liane C.J., Terpstra, Valeska, Bohmer, Lara H., Nicolae, Alina, Posthuma, Eduardus F.M., Koens, Lianne, Durian, Marc F., Stavast, Jeroen, van der Poel, Marjolein W.M., Hamid, Myrurgia Abdul, Stevens, Wendy B.C., van Rooij, Sjo L.M., Oostvogels, Rimke S., Mühlebner, Angelika, Neelis, Karen J., van den Brand, Michiel, Tousseyn, Thomas, Dierickx, Daan, de Weerdt, Okke, Beeker, Aart, Jansen, Patty M., Kersten, Marie José, Zijlstra, Josée M., Chamuleau, Martine E.D., Veelken, Hendrik, Bromberg, Jacoline C.E., Nijland, Marcel, and Vermaat, Joost S.P.

Published
2024
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3. Treatment strategies and outcome in relapsed peripheral T-cell lymphoma: results from the Netherlands Cancer Registry

Author

Brink, Mirian, primary, Huisman, Francien, additional, Meeuwes, Frederik Okko, additional, van der Poel, Marjolein W.M, additional, Kersten, Marie José, additional, Wondergem, Marielle J, additional, Bohmer, Lara H., additional, Woei-A-Jin, F.J. Sherida H., additional, Visser, Otto J., additional, Oostvogels, Rimke, additional, Jansen, Patty M, additional, Diepstra, Arjan, additional, Snijders, Tjeerd J.F., additional, Huls, Gerwin A, additional, Vermaat, Joost S.P., additional, Plattel, Wouter J., additional, and Nijland, Marcel, additional

Published
2024
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4. Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype

Author

de Groen, Ruben A.L., van Eijk, Ronald, Böhringer, Stefan, van Wezel, Tom, Raghoo, Richard, Ruano, Dina, Jansen, Patty M., Briaire-de Bruijn, Inge, de Groot, Fleur A., Kleiverda, Karin, te Boome, Liane, Terpstra, Valeska, Levenga, Henriette, Nicolae, Alina, Posthuma, Eduardus F.M., Focke-Snieders, Isabelle, Hardi, Lizan, den Hartog, Wietske C.E., Bohmer, Lara H., Hogendoorn, Pancras C.W., van den Berg, Anke, Diepstra, Arjan, Nijland, Marcel, Lugtenburg, Pieternella J., Kersten, Marie José, Pals, Steven T., Veelken, Hendrik, Bovée, Judith V.M.G., Cleven, Arjen H.G., and Vermaat, Joost S.P.

Published
2021
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5. Frequent mutated B2M, EZH2, IRF8, and TNFRSF14 in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype

Author

de Groen, A. L., van Eijk, Ronald, Bohringer, Stefan, Wezel, Tom van, Raghoo, Richard, Ruano, Dina, Jansen, Patty M., Briaire-De Bruijn, Inge, de Groot, Fleur A., Kleiverda, Karin, te Boome, Liane, Terpstra, Valeska, Levenga, Henriette, Nicolae, Alina, Posthuma, Eduardus F.M., Focke-Snieders, Isabelle, Hardi, Lizan, den Hartog, Wietske C.E., Bohmer, Lara H., Hogendoorn, Pancras C.W., den Berg, Anke van, Diepstra, Arjan, Nijland, Marcel, Lugtenburg, Pieternella J., Kersten, Marie Jose, Pals, Steven T., Veelken, Hendrik, Bovee, Judith V.M.G., Cleven, Arjen H.G., Vermaat, Joost S.P., de Groen, A. L., van Eijk, Ronald, Bohringer, Stefan, Wezel, Tom van, Raghoo, Richard, Ruano, Dina, Jansen, Patty M., Briaire-De Bruijn, Inge, de Groot, Fleur A., Kleiverda, Karin, te Boome, Liane, Terpstra, Valeska, Levenga, Henriette, Nicolae, Alina, Posthuma, Eduardus F.M., Focke-Snieders, Isabelle, Hardi, Lizan, den Hartog, Wietske C.E., Bohmer, Lara H., Hogendoorn, Pancras C.W., den Berg, Anke van, Diepstra, Arjan, Nijland, Marcel, Lugtenburg, Pieternella J., Kersten, Marie Jose, Pals, Steven T., Veelken, Hendrik, Bovee, Judith V.M.G., Cleven, Arjen H.G., and Vermaat, Joost S.P.

Published
2021

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

Author

Chamuleau, Martine E.D., Burggraaff, Coreline N., Nijland, Marcel, Bakunina, Katerina, Mous, Rogier, Lugtenburg, Pieternella J., Dierickx, Daan, van Imhoff, Gustaaf W., Vermaat, Joost S.P., Marijt, Eric A.F., Visser, Otto, Mandigers, Caroline, Bilgin, Yavuz M., Beeker, Aart, Durian, Mark F., van Rees, Bas P., Bohmer, Lara H., Tick, Lidwine W., Boersma, Rinske S., Snijders, Tjeerd J.F., Schouten, Harry C., Koene, Harry R., de Jongh, Eva, Hijmering, Nathalie, Diepstra, Arjan, van de Berg, Anke, Arens, Anne I.J., Huijbregts, Julia, Hoekstra, Otto, Zijlstra, Josee M., de Jong, Daphne, and Kersten, Marie José

Abstract

atients 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 without MYC 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 18F-fluorodeoxyglucose (18F-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).

Published
2020

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

Author

Chamuleau, Martine E. D., Burggraaff, Coreline N., Nijland, Marcel, Bakunina, Katerina, Mous, Rogier, Lugtenburg, Pieternella J., Dierickx, Daan, van Imhoff, Gustaaf W., Vermaat, Joost S. P., Marijt, Eric A. F., Visser, Otto, Mandigers, Caroline, Bilgin, Yavuz M., Beeker, Aart, Durian, Mark F., van Rees, Bas P., Bohmer, Lara H., Tick, Lidwine W., Boersma, Rinske S., Snijders, Tjeerd J. F., Schouten, Harry C., Koene, Harry R., de Jongh, Eva, Hijmering, Nathalie, Diepstra, Arjan, van de Berg, Anke, Arens, Anne I. J., Huijbregts, Julia, Hoekstra, Otto, Zijlstra, Josee M., de Jong, Daphne, Kersten, Marie José, Hematology, CCA - Cancer Treatment and quality of life, Internal medicine, Oral and Maxillofacial Surgery / Oral Pathology, Pathology, Radiology and nuclear medicine, CCA - Imaging and biomarkers, AGEM - Re-generation and cancer of the digestive system, AII - Cancer immunology, Erasmus MC other, Radiotherapy, Clinical Haematology, and CCA - Cancer Treatment and Quality of Life

Abstract

atients 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 without MYC 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 18F-fluorodeoxyglucose (18F-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).

Published
2020

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

Author

Stamceltransplantatieteam, MS Hematologie, Infection & Immunity, Cancer, Chamuleau, Martine E.D., Burggraaff, Coreline N., Nijland, Marcel, Bakunina, Katerina, Mous, Rogier, Lugtenburg, Pieternella J., Dierickx, Daan, van Imhoff, Gustaaf W., Vermaat, Joost S.P., Marijt, Eric A.F., Visser, Otto, Mandigers, Caroline, Bilgin, Yavuz M., Beeker, Aart, Durian, Mark F., van Rees, Bas P., Bohmer, Lara H., Tick, Lidwine W., Boersma, Rinske S., Snijders, Tjeerd J.F., Schouten, Harry C., Koene, Harry R., de Jongh, Eva, Hijmering, Nathalie, Diepstra, Arjan, van de Berg, Anke, Arens, Anne I.J., Huijbregts, Julia, Hoekstra, Otto, Zijlstra, Josee M., de Jong, Daphne, Kersten, Marie José, Stamceltransplantatieteam, MS Hematologie, Infection & Immunity, Cancer, Chamuleau, Martine E.D., Burggraaff, Coreline N., Nijland, Marcel, Bakunina, Katerina, Mous, Rogier, Lugtenburg, Pieternella J., Dierickx, Daan, van Imhoff, Gustaaf W., Vermaat, Joost S.P., Marijt, Eric A.F., Visser, Otto, Mandigers, Caroline, Bilgin, Yavuz M., Beeker, Aart, Durian, Mark F., van Rees, Bas P., Bohmer, Lara H., Tick, Lidwine W., Boersma, Rinske S., Snijders, Tjeerd J.F., Schouten, Harry C., Koene, Harry R., de Jongh, Eva, Hijmering, Nathalie, Diepstra, Arjan, van de Berg, Anke, Arens, Anne I.J., Huijbregts, Julia, Hoekstra, Otto, Zijlstra, Josee M., de Jong, Daphne, and Kersten, Marie José

Published
2020

9. Rituximab-chop with early rituximab intensification for diffuse large b-cell lymphoma: A randomized phase iii trial of the hovon and the nordic lymphoma group (hovon-84)

Author

MS Radiologie, Cancer, Lugtenburg, Pieternella Johanna, De Nully Brown, Peter, Van der Holt, Bronno, D'Amore, Francesco A., Koene, Harry R., De Jongh, Eva, Fijnheer, Rob, Van Esser, Joost W., Bohmer, Lara H., Pruijt, Johannes F., Verhoef, Gregor E., Hoogendoorn, Mels, Bilgin, Memis Y., Nijland, Marcel, Van der Burg-De Graauw, Nicole C., Oosterveld, Margreet, Jie, Kon Siong G., Larsen, Thomas Stauffer, Van der Poel, Marjolein W., Leijs, Maria B., Silbermann, Matthijs H., Van Marwijk Kooy, Marinus, Beeker, Aart, Kersten, Marie J., Doorduijn, Jeanette K., Tick, Lidwine W., Brouwer, Rolf E., Lam, King H., Burggraaff, Coreline N., De Keizer, Bart, Arens, Anne I., De Jong, Daphne, Hoekstra, Otto S., Zijlstra-Baalbergen, Josee M., MS Radiologie, Cancer, Lugtenburg, Pieternella Johanna, De Nully Brown, Peter, Van der Holt, Bronno, D'Amore, Francesco A., Koene, Harry R., De Jongh, Eva, Fijnheer, Rob, Van Esser, Joost W., Bohmer, Lara H., Pruijt, Johannes F., Verhoef, Gregor E., Hoogendoorn, Mels, Bilgin, Memis Y., Nijland, Marcel, Van der Burg-De Graauw, Nicole C., Oosterveld, Margreet, Jie, Kon Siong G., Larsen, Thomas Stauffer, Van der Poel, Marjolein W., Leijs, Maria B., Silbermann, Matthijs H., Van Marwijk Kooy, Marinus, Beeker, Aart, Kersten, Marie J., Doorduijn, Jeanette K., Tick, Lidwine W., Brouwer, Rolf E., Lam, King H., Burggraaff, Coreline N., De Keizer, Bart, Arens, Anne I., De Jong, Daphne, Hoekstra, Otto S., and Zijlstra-Baalbergen, Josee M.

Published
2020

10. Rituximab-PECC induction followed by Y-90-ibritumomab tiuxetan consolidation in relapsed or refractory DLBCL patients who are ineligible for or have failed ASCT: results from a phase II HOVON study

Author

Lugtenburg, Pieternella J., Zijlstra, Josee M., Doorduijn, Jeanette K., Bohmer, Lara H., Hoogendoorn, Mels, Berenschot, Henriette W., Beeker, Aart, van der Burg-de Graauw, Nicole C., Schouten, Harry C., Bilgin, Yavuz M., Kersten, Marie-Jose, Koene, Harry R., Herbers, Alexandra H. E., de Jong, Daphne, Hijmering, Nathalie, Lam, King H., Chitu, Dana, Brouwer, Rolf E., and van Imhoff, Gustaaf W.

Subjects
relapse, PLUS RITUXIMAB, IBRITUMOMAB TIUXETAN, diffuse large B-cell lymphoma, MULTICENTER, B-CELL LYMPHOMA, PECC, CHEMOTHERAPY, OPEN-LABEL, TRIAL, Y-90-ibritumomab tiuxetan, COMBINATION, consolidation, ELDERLY-PATIENTS, CHOP
Abstract

Patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after, or ineligible for, autologous stem cell transplantation (ASCT) have a dismal prognosis. This phase II study evaluated treatment with R-PECC (rituximab, prednisolone, etoposide, chlorambucil, lomustine), every 28 days for 4 cycles in 62 patients, followed by radio-immunotherapy consolidation with Y-90-ibritumomab tiuxetan in responsive patients. Primary endpoints were failure-free survival (FFS) and incidence of grade >= 3 adverse events from start of Y-90-ibritumomab tiuxetan. The overall response rate after R-PECC was 50%. Twenty-nine of 31 responsive patients proceeded to Y-90-ibritumomab tiuxetan. Five out of 15 partial remission patients converted to complete remission after Y-90-ibritumomab tiuxetan. One-year FFS and overall survival (OS) from start of Y-90-ibritumomab tiuxetan was 52% (95% confidence interval [CI], 33-68%) and 62% (95% CI, 42-77%), respectively. One-year FFS and OS from start of R-PECC was 28% (95% CI, 17-39%) and 49% (95% CI, 36-61%), respectively. Toxicities of R-PECC and Y-90-ibritumomab tiuxetan were mainly haematological. In conclusion, for relapsed DLBCL patients the largely oral R-PECC regimen achieves promising response rates, combined with an acceptable safety profile. Consolidation with Y-90-ibritumomab tiuxetan resulted in long-term response durations in approximately one third of the patients that received it.

Published
2019

11. Ixazomib, Rituximab and Dexamethasone (IRD) in Patients with Relapsed or Progressive Waldenstrom's Macroblobulinemia: Results of the Prospective Phase I/II HOVON 124/Ecwm-R2 Trial

Author

Kersten, Marie Jose Minnema, Monique C. Vos, Josephine M. and Nasserinejad, Kazem Kap, Marcel Kastritis, Eftathios and Gavriatopoulou, Maria Chamuleau, Martine E. D. Deeren, Dries and Tick, Lidwine Winnifred Doorduijn, Jeanette K. Offner, Fritz and Bohmer, Lara H. Amaador, Karima Liu, Roberto D. Pals, Steven T. Dimopoulos, Meletios A.

Published
2019

12. Ixazomib, Rituximab and Dexamethasone (IRD) in Patients with Relapsed or Progressive Waldenstrom's Macroblobulinemia: Results of the Prospective Phase I/II HOVON 124/Ecwm-R2 Trial

Author

Kersten, Marie José, primary, Minnema, Monique C., primary, Vos, Josephine M., primary, Nasserinejad, Kazem, primary, Kap, Marcel, primary, Kastritis, Eftathios, primary, Gavriatopoulou, Maria, primary, Chamuleau, Martine E.D., primary, Deeren, Dries, primary, Tick, Lidwine Winnifred, primary, Doorduijn, Jeanette K., primary, Offner, Fritz, primary, Bohmer, Lara H, primary, Amaador, Karima, primary, Liu, Roberto D, primary, Pals, Steven T, primary, and Dimopoulos, Meletios A., primary

Published
2019
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13. Frequent mutated B2M, EZH2, IRF8, and TNFRSF14in primary bone diffuse large B-cell lymphoma reflect a GCB phenotype

Author

de Groen, Ruben A.L., van Eijk, Ronald, Böhringer, Stefan, van Wezel, Tom, Raghoo, Richard, Ruano, Dina, Jansen, Patty M., Briaire-de Bruijn, Inge, de Groot, Fleur A., Kleiverda, Karin, te Boome, Liane, Terpstra, Valeska, Levenga, Henriette, Nicolae, Alina, Posthuma, Eduardus F.M., Focke-Snieders, Isabelle, Hardi, Lizan, den Hartog, Wietske C.E., Bohmer, Lara H., Hogendoorn, Pancras C.W., van den Berg, Anke, Diepstra, Arjan, Nijland, Marcel, Lugtenburg, Pieternella J., Kersten, Marie José, Pals, Steven T., Veelken, Hendrik, Bovée, Judith V.M.G., Cleven, Arjen H.G., and Vermaat, Joost S.P.

Abstract

Primary bone diffuse large B-cell lymphoma (PB-DLBCL) is a rare extranodal lymphoma subtype. This retrospective study elucidates the currently unknown genetic background of a large clinically well-annotated cohort of DLBCL with osseous localizations (O-DLBCL), including PB-DLBCL. A total of 103 patients with O-DLBCL were included and compared with 63 (extra)nodal non-osseous (NO)-DLBCLs with germinal center B-cell phenotype (NO-DLBCL-GCB). Cell-of-origin was determined by immunohistochemistry and gene-expression profiling (GEP) using (extended)-NanoString/Lymph2Cx analysis. Mutational profiles were identified with targeted next-generation deep sequencing, including 52 B-cell lymphoma-relevant genes. O-DLBCLs, including 34 PB-DLBCLs, were predominantly classified as GCB phenotype based on immunohistochemistry (74%) and NanoString analysis (88%). Unsupervised hierarchical clustering of an extended-NanoString/Lymph2Cx revealed significantly different GEP clusters for PB-DLBCL as opposed to NO-DLBCL-GCB (P< .001). Expression levels of 23 genes of 2 different targeted GEP panels indicated a centrocyte-like phenotype for PB-DLBCL, whereas NO-DLBCL-GCB exhibited a centroblast-like constitution. PB-DLBCL had significantly more frequent mutations in four GCB-associated genes (ie, B2M, EZH2, IRF8, TNFRSF14) compared with NO-DLBCL-GCB (P= .031, P= .010, P= .047, and P= .003, respectively). PB-DLBCL, with its corresponding specific mutational profile, was significantly associated with a superior survival compared with equivalent Ann Arbor limited-stage I/II NO-DLBCL-GCB (P= .016). This study is the first to show that PB-DLBCL is characterized by a GCB phenotype, with a centrocyte-like GEP pattern and a GCB-associated mutational profile (both involved in immune surveillance) and a favorable prognosis. These novel biology-associated features provide evidence that PB-DLBCL represents a distinct extranodal DLBCL entity, and its specific mutational landscape offers potential for targeted therapies (eg, EZH2 inhibitors).

Published
2021
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14. Randomized phase III study on the effect of early intensification of rituximab in combination with 2-weekly CHOP chemotherapy followed by rituximab or no maintenance in patients with diffuse large B-cell lymphoma: Results from a HOVON-Nordic Lymphoma Group study.

Author

Lugtenburg, Pieternella J., primary, de Nully Brown, Peter, additional, van der Holt, Bronno, additional, D'Amore, Francesco, additional, Koene, Harry R, additional, Berenschot, Henriette W, additional, Fijnheer, Rob, additional, Loosveld, Olaf, additional, Bohmer, Lara H, additional, Pruijt, Hans, additional, Verhoef, Gregor, additional, Hoogendoorn, Mels, additional, de Kan, Romko, additional, Van Imhoff, Gustaaf Willem, additional, van Hooije, Christel, additional, Lam, King H, additional, de Keizer, Bart, additional, de Jong, Daphne, additional, Hoekstra, Otto S., additional, and Zijlstra, Josee M, additional

Published
2016
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15. Treatment of patients with MYC rearrangement positive large B-cell lymphoma with R-CHOP plus lenalidomide: results of a multicenter HOVON phase II trial.

Author

Chamuleau MED, Burggraaff CN, Nijland M, Bakunina K, Mous R, Lugtenburg PJ, Dierickx D, van Imhoff GW, Vermaat JSP, Marijt EAF, Visser O, Mandigers C, Bilgin YM, Beeker A, Durian MF, van Rees B, Bohmer LH, Tick LW, Boersma RS, Snijders TJF, Schouten HC, Koene HR, de Jongh E, Hijmering N, Diepstra A, van den Berg A, Arens AIJ, Huijbregts J, Hoekstra O, Zijlstra JM, de Jong D, and Kersten MJ

Subjects
Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Humans, Lenalidomide therapeutic use, Prednisone therapeutic use, Prospective Studies, Rituximab therapeutic use, Treatment Outcome, Vincristine therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse genetics
Abstract

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) as compared to patients without MYC 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 MYC-FISH screening program. The primary endpoint was complete metabolic response (CMR) on centrally reviewed 18F-fluorodeoxyglucose (18F-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 6 cycles of R2CHOP. At EOT, 67% (confidence interval (CI) 58-75%) of the patients reached CMR. With a median follow-up of 25.4 months, 2-year estimates (95% CI) for OS, DFS, EFS were 73% (62-82%), 75% (63-84%) and 63% (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).

Published
2020
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