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245 results on '"Breems, Dimitri A."'

1. Midostaurin added to 10-day decitabine, for patients unfit for intensive chemotherapy with AML and higher risk MDS, irrespective of FLT3 mutational status, does not improve outcome

Author

Huls, Gerwin, Chitu, Dana A., Tick, Lidwine, Boersma, Rinske, Breems, Dimitri, Herbers, Alexandra, Klein, Saskia K., de Jonge, Suzan, Westerweel, Peter E., Cruijsen, Marjan, Hoogendoorn, Mels, Cuijpers, Marlous, Deeren, Dries, Bailly, Benjamin, Visser, Otto, van Rhenen, Anna, Posthuma, Eduard F. M., Valk, Peter J. M., Cloos, Jacqueline, Ammatuna, Emanuele, Refos, Jeannine M., Fakkert, R., Löwenberg, Bob, and Ossenkoppele, Gert J.

Published
2024
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2. Bayesian interim analysis for prospective randomized studies: reanalysis of the acute myeloid leukemia HOVON 132 clinical trial

Author

van der Maas, Niek G., Versluis, Jurjen, Nasserinejad, Kazem, van Rosmalen, Joost, Pabst, Thomas, Maertens, Johan, Breems, Dimitri, Manz, Markus, Cloos, Jacqueline, Ossenkoppele, Gert J., Floisand, Yngvar, Gradowska, Patrycja, Löwenberg, Bob, Huls, Gerwin, Postmus, Douwe, Pignatti, Francesco, and Cornelissen, Jan J.

Published
2024
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3. Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Author

Hilberink, Jacobien R., van Zeventer, Isabelle A., Chitu, Dana A., Pabst, Thomas, Klein, Saskia K., Stussi, Georg, Griskevicius, Laimonas, Valk, Peter J. M., Cloos, Jacqueline, van de Loosdrecht, Arjan A., Breems, Dimitri, van Lammeren-Venema, Danielle, Boersma, Rinske, Jongen-Lavrencic, Mojca, Fehr, Martin, Hoogendoorn, Mels, Manz, Markus G., Söhne, Maaike, van Marwijk Kooy, Rien, Deeren, Dries, van der Poel, Marjolein W. M., Legdeur, Marie Cecile, Tick, Lidwine, Chalandon, Yves, Ammatuna, Emanuele, Blum, Sabine, Löwenberg, Bob, Ossenkoppele, Gert J., and Huls, Gerwin

Published
2023
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4. A phase 1b study of glasdegib + azacitidine in patients with untreated acute myeloid leukemia and higher-risk myelodysplastic syndromes

Author

Sekeres, Mikkael A., Schuster, Michael, Joris, Magalie, Krauter, Jürgen, Maertens, Johan, Breems, Dimitri, Gyan, Emmanuel, Kovacsovics, Tibor, Verma, Amit, Vyas, Paresh, Wang, Eunice S., Ching, Keith, O’Brien, Thomas, Gallo Stampino, Corrado, Ma, Weidong Wendy, Kudla, Arthur, Chan, Geoffrey, and Zeidan, Amer M.

Published
2022
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5. Molecular characterization of mutant TP53 acute myeloid leukemia and high-risk myelodysplastic syndrome

Author

Grob, Tim, Al Hinai, Adil S.A., Sanders, Mathijs A., Kavelaars, François G., Rijken, Melissa, Gradowska, Patrycja L., Biemond, Bart J., Breems, Dimitri A., Maertens, Johan, van Marwijk Kooy, Marinus, Pabst, Thomas, de Weerdt, Okke, Ossenkoppele, Gert J., van de Loosdrecht, Arjan A., Huls, Gerwin A., Cornelissen, Jan J., Beverloo, H. Berna, Löwenberg, Bob, Jongen-Lavrencic, Mojca, and Valk, Peter J.M.

Published
2022
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6. Clofarabine added to intensive treatment in adult patients with newly diagnosed ALL: the HOVON-100 trial

Author

Rijneveld, Anita W., van der Holt, Bronno, de Weerdt, Okke, Biemond, Bart J., van de Loosdrecht, Arjen A., van der Wagen, Lotte E., Bellido, Mar, van Gelder, Michel, van der Velden, Walter J.F.M., Selleslag, Dominik, van Lammeren-Venema, Daniëlle, Halkes, Constantijn J.M., Fijnheer, Rob, Havelange, Violaine, van Sluis, Geerte L., Legdeur, Marie-Cecile, Deeren, Dries, Gadisseur, Alain, Sinnige, Harm A.M., Breems, Dimitri A., Jaspers, Aurélie, Legrand, Ollivier, Terpstra, Wim E., Boersma, Rinske S., Mazure, Dominiek, Triffet, Agnes, Tick, Lidwine W., Beel, Karolien, Maertens, Johan A., Beverloo, H. Berna, Bakkus, Marleen, Homburg, Christa H.E., de Haas, Valerie, van der Velden, Vincent H.J., and Cornelissen, Jan J.

Published
2022
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7. Moxetumomab pasudotox in relapsed/refractory hairy cell leukemia.

Author

Kreitman, Robert, Dearden, Claire, Zinzani, Pier, Delgado, Julio, Karlin, Lionel, Robak, Tadeusz, Gladstone, Douglas, le Coutre, Philipp, Dietrich, Sascha, Gotic, Mirjana, Larratt, Loree, Offner, Fritz, Schiller, Gary, Swords, Ronan, Bacon, Larry, Bocchia, Monica, Bouabdallah, Krimo, Breems, Dimitri, Cortelezzi, Agostino, Dinner, Shira, Doubek, Michael, Gjertsen, Bjorn, Gobbi, Marco, Hellmann, Andrzej, Lepretre, Stephane, Maloisel, Frederic, Ravandi, Farhad, Rousselot, Philippe, Rummel, Mathias, Siddiqi, Tanya, Tadmor, Tamar, Troussard, Xavier, Yi, Cecilia, Saglio, Giuseppe, Roboz, Gail, Balic, Kemal, Standifer, Nathan, He, Peng, Marshall, Shannon, Wilson, Wyndham, Pastan, Ira, Yao, Nai-Shun, and Giles, Francis

Subjects
Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Bacterial Toxins, Drug Resistance, Neoplasm, Exotoxins, Female, Follow-Up Studies, Humans, Leukemia, Hairy Cell, Male, Middle Aged, Neoplasm Recurrence, Local, Prognosis, Remission Induction, Salvage Therapy, Survival Rate
Abstract

This is a pivotal, multicenter, open-label study of moxetumomab pasudotox, a recombinant CD22-targeting immunotoxin, in hairy cell leukemia (HCL), a rare B cell malignancy with high CD22 expression. The study enrolled patients with relapsed/refractory HCL who had ≥2 prior systemic therapies, including ≥1 purine nucleoside analog. Patients received moxetumomab pasudotox 40 µg/kg intravenously on days 1, 3, and 5 every 28 days for ≤6 cycles. Blinded independent central review determined disease response and minimal residual disease (MRD) status. Among 80 patients (79% males; median age, 60.0 years), durable complete response (CR) rate was 30%, CR rate was 41%, and objective response rate (CR and partial response) was 75%; 64 patients (80%) achieved hematologic remission. Among complete responders, 27 (85%) achieved MRD negativity by immunohistochemistry. The most frequent adverse events (AEs) were peripheral edema (39%), nausea (35%), fatigue (34%), and headache (33%). Treatment-related serious AEs of hemolytic uremic syndrome (7.5%) and capillary leak syndrome (5%) were reversible and generally manageable with supportive care and treatment discontinuation (6 patients; 7.5%). Moxetumomab pasudotox treatment achieved a high rate of independently assessed durable response and MRD eradication in heavily pretreated patients with HCL, with acceptable tolerability.

Published
2018

8. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial

Author

Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J., Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W., Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J.F.M., Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W.J., Bargetzi, Mario, Klein, Saskia K., Gadisseur, Alain, Westerweel, Peter E., Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A., Hoogendoorn, Mels, Legdeur, Marie-Cecile J.C., Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T., Janssen, Jeroen J.W.M., Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J.M., van Elssen, Catharina H.M.J., Manz, Markus G., Floisand, Yngvar, and Ossenkoppele, Gert J.

Published
2021
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9. Bayesian interim analysis for prospective randomized studies:reanalysis of the acute myeloid leukemia HOVON 132 clinical trial

Author

van der Maas, Niek G., Versluis, Jurjen, Nasserinejad, Kazem, van Rosmalen, Joost, Pabst, Thomas, Maertens, Johan, Breems, Dimitri, Manz, Markus, Cloos, Jacqueline, Ossenkoppele, Gert J., Floisand, Yngvar, Gradowska, Patrycja, Löwenberg, Bob, Huls, Gerwin, Postmus, Douwe, Pignatti, Francesco, Cornelissen, Jan J., van der Maas, Niek G., Versluis, Jurjen, Nasserinejad, Kazem, van Rosmalen, Joost, Pabst, Thomas, Maertens, Johan, Breems, Dimitri, Manz, Markus, Cloos, Jacqueline, Ossenkoppele, Gert J., Floisand, Yngvar, Gradowska, Patrycja, Löwenberg, Bob, Huls, Gerwin, Postmus, Douwe, Pignatti, Francesco, and Cornelissen, Jan J.

Abstract

Randomized controlled trials (RCTs) are the gold standard to establish the benefit-risk ratio of novel drugs. However, the evaluation of mature results often takes many years. We hypothesized that the addition of Bayesian inference methods at interim analysis time points might accelerate and enforce the knowledge that such trials may generate. In order to test that hypothesis, we retrospectively applied a Bayesian approach to the HOVON 132 trial, in which 800 newly diagnosed AML patients aged 18 to 65 years were randomly assigned to a “7 + 3” induction with or without lenalidomide. Five years after the first patient was recruited, the trial was negative for its primary endpoint with no difference in event-free survival (EFS) between experimental and control groups (hazard ratio [HR] 0.99, p = 0.96) in the final conventional analysis. We retrospectively simulated interim analyses after the inclusion of 150, 300, 450, and 600 patients using a Bayesian methodology to detect early lack of efficacy signals. The HR for EFS comparing the lenalidomide arm with the control treatment arm was 1.21 (95% CI 0.81–1.69), 1.05 (95% CI 0.86–1.30), 1.00 (95% CI 0.84–1.19), and 1.02 (95% CI 0.87–1.19) at interim analysis 1, 2, 3 and 4, respectively. Complete remission rates were lower in the lenalidomide arm, and early deaths more frequent. A Bayesian approach identified that the probability of a clinically relevant benefit for EFS (HR < 0.76, as assumed in the statistical analysis plan) was very low at the first interim analysis (1.2%, 0.6%, 0.4%, and 0.1%, respectively). Similar observations were made for low probabilities of any benefit regarding CR. Therefore, Bayesian analysis significantly adds to conventional methods applied for interim analysis and may thereby accelerate the performance and completion of phase III trials.

Published
2024

10. Prospective validation of the prognostic relevance of CD34+CD38– AML stem cell frequency in the HOVON-SAKK132 trial

Author

Ngai, Lok Lam, Hanekamp, Diana, Janssen, Fleur, Carbaat-Ham, Jannemieke, Hofland, Maaike A M, Fayed, Mona M H E, Kelder, Angèle, Oudshoorn-van Marsbergen, Laura, Scholten, Willemijn J, Snel, Alexander N, Bachas, Costa, Tettero, Jesse M, Breems, Dimitri A, Fischer, Thomas, Gjertsen, Bjorn T, Griskevicius, Laimonas, Juliusson, Gunnar, van de Loosdrecht, Arjan A, Maertens, Johan A, Manz, Markus G, Pabst, Thomas, Passweg, Jakob R, Porkka, Kimmo, Valk, Peter J M, Gradowska, Patrycja, Löwenberg, Bob, de Leeuw, David C, Janssen, Jeroen J W M, Ossenkoppele, Gert J, Cloos, Jacqueline, Hematology laboratory, VU University medical center, Hematology, AII - Cancer immunology, AII - Inflammatory diseases, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, and CCA - Cancer Treatment and quality of life

Subjects
All institutes and research themes of the Radboud University Medical Center, Immunology, Cell Biology, Hematology, 610 Medicine & health, Biochemistry, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9]
Abstract

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Published
2023

12. S249: SELECTIVE JAK2/IRAK1/ACVR1 INHIBITOR PACRITINIB BEFORE REDUCED-INTENSITY CONDITIONING ALLOGENEIC STEM CELL TRANSPLANTATION IN MYELOFIBROSIS: FINAL ANALYSIS OF THE PHASE II HOVON-134 TRIAL

Author

Van Dijck, Ruben, primary, VAN DER Holt, Ron, additional, Meijer, Ellen, additional, Devos, Timothy, additional, Hazenberg, Mette, additional, Van Der Poel, Marjolein, additional, Breems, Dimitri, additional, Deleu, Lien, additional, Schaap, Nicolaas, additional, and Te Boekhorst, Peter André Willem, additional

Published
2023
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13. P565: REAL-WORLD DATA AS SUPPLEMENTARY CONTROLS FOR THE PROSPECTIVE RANDOMIZED HOVON-103 TRIAL IN INTENSIVELY TREATED ELDERLY ACUTE MYELOID LEUKEMIA PATIENTS

Author

Hermans, Sjoerd, primary, van Norden, Yvette, additional, van Werkhoven, Erik, additional, Dinmohamed, Avinash, additional, Huijgens, Peter, additional, Ossenkoppele, Gert, additional, Huls, Gerwin, additional, Löwenberg, Bob, additional, Pabst, Thomas, additional, Breems, Dimitri, additional, Postmus, Douwe, additional, Pignatti, Francesco, additional, Versluis, Jurjen, additional, and Cornelissen, Jan, additional

Published
2023
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14. P432: VALIDATION OF LIMIT OF QUANTIFICATION APPROACH BASED FLOW CYTOMETRY FOR MEASURABLE RESIDUAL DISEASE ASSESSMENT IN ACUTE MYELOID LEUKEMIA IN THE HOVON-SAKK-132 TRIAL

Author

Tettero, Jesse, primary, Palmieri, Raffaele, additional, Lam Ngai, Lok, additional, Bachas, Costa, additional, Arena, Valentina, additional, Breems, Dimitri, additional, Fischer, Thomas, additional, Tore Gjertsen, Bjorn, additional, Griškevičius, Laimonas, additional, Juliusson, Gunnar, additional, Maertens, Johan, additional, Manz, Markus, additional, Maurillo, Luca, additional, Pabst, Thomas, additional, Passweg, Jakob, additional, Piciocchi, Alfonso, additional, Porkka, Kimmo, additional, Löwenberg, Bob, additional, Venditti, Adriano, additional, Ossenkoppele, Gert, additional, Buccisano, Francesco, additional, and Cloos, Jacqueline, additional

Published
2023
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15. P475: EMERGING LEUKEMIA ASSOCIATED IMMUNOPHENOTYPES (LAIPS) IN BONE MARROW OF ACUTE MYELOID LEUKEMIA PATIENTS AFTER INTENSIVE CHEMOTHERAPY.

Author

Lam Ngai, Lok, primary, Hanekamp, Diana, additional, Kelder, Angèle, additional, Scholten, Willemijn J., additional, Carbaat - Ham, Jannemieke, additional, Snel, Alexander N., additional, Bachas, Costa, additional, Tettero, Jesse, additional, van der Velden, Vincent, additional, Slomp, Jennichjen, additional, Hobo, Willemijn, additional, Breems, Dimitri, additional, Fischer, Thomas, additional, Tore Gjertsen, Bjorn, additional, Griškevičius, Laimonas, additional, Juliusson, Gunnar, additional, Maertens, Johan, additional, Manz, Markus, additional, Pabst, Thomas, additional, Passweg, Jakob, additional, Porkka, Kimmo, additional, Valk, Peter, additional, Gradowska, Patrycja, additional, Löwenberg, Bob, additional, de Leeuw, David, additional, van de Loosdrecht, Arjan, additional, Ossenkoppele, Gert, additional, and Cloos, Jacqueline, additional

Published
2023
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16. P1608: REAL-WORLD INSIGHTS ON THE MANAGEMENT OF IMMUNE-MEDIATED THROMBOTIC THROMBOCYTOPENIC PURPURA (ITTP) WITH CAPLACIZUMAB IN BELGIUM

Author

Dierickx, Daan, primary, Connerotte, Thierry, additional, Dallemagne, Julie, additional, Becker, Ann De, additional, Moors, Ine, additional, Snauwaert, Sylvia, additional, Sonet, Anne, additional, Theunissen, Koen, additional, Breems, Dimitri, additional, Prijck, Bernard De, additional, Jaspers, Aurélie, additional, Lambert, Catherine, additional, Heyrman, Bert, additional, Hautekiet, Joris, additional, Lyna, Sofie, additional, Maertens, Chantal, additional, and Delrieu, Vanessa, additional

Published
2023
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18. CD34+CD38− leukemic stem cell frequency to predict outcome in acute myeloid leukemia

Author

Zeijlemaker, Wendelien, Grob, Tim, Meijer, Rosa, Hanekamp, Diana, Kelder, Angèle, Carbaat-Ham, Jannemieke C., Oussoren-Brockhoff, Yvonne J. M., Snel, Alexander N., Veldhuizen, Dennis, Scholten, Willemijn J., Maertens, Johan, Breems, Dimitri A., Pabst, Thomas, Manz, Markus G., van der Velden, Vincent H. J., Slomp, Jennichjen, Preijers, Frank, Cloos, Jacqueline, van de Loosdrecht, Arjan A., Löwenberg, Bob, Valk, Peter J. M., Jongen-Lavrencic, Mojca, Ossenkoppele, Gert J., and Schuurhuis, Gerrit J.

Published
2019
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19. Disease Perception Is Correlated with Health-Related Quality of Life in Patients Suffering from Myelodysplastic Syndromes: Results of the Belgian Be-QUALMS Study

Author

Heyrman, Bert, primary, Meers, Stef, additional, De Becker, Ann, additional, Wouters, Kristien, additional, Van Hoof, Achiel, additional, Van De Velde, Ann, additional, Graux, Carlos, additional, Mazure, Dominiek, additional, Selleslag, Dominik, additional, Maes, Helena, additional, Lemmens, Jan, additional, Beckers, Marielle, additional, Breems, Dimitri, additional, Sid, Sélim, additional, Berneman, Zwi, additional, and Anguille, Sébastien, additional

Published
2023
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20. Therapeutic value of clofarabine in younger and middle-aged (18-65 years) adults with newly diagnosed AML

Author

Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, van Norden, Yvette, Biemond, Bart J., Schouten, Harry C., Spertini, Olivier, Vellenga, Edo, Graux, Carlos, Havelange, Violaine, de Greef, Georgine E., de Weerdt, Okke, Legdeur, Marie-Cecile J.C., Kuball, Juergen, Kooy, Marinus van Marwijk, Gjertsen, Bjorn T., Jongen-Lavrencic, Mojca, van de Loosdrecht, Arjan A., van Lammeren-Venema, Daniëlle, Hodossy, Beata, Breems, Dimitri A., Chalandon, Yves, Passweg, Jakob, Valk, Peter J.M., Manz, Markus G., and Ossenkoppele, Gert J.

Published
2017
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21. Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Author

Hilberink, Jacobien R, van Zeventer, Isabelle A, Chitu, Dana A, Pabst, Thomas, Klein, Saskia K, Stussi, Georg, Griskevicius, Laimonas, Valk, Peter J M, Cloos, Jacqueline, van de Loosdrecht, Arjan A, Breems, Dimitri, van Lammeren-Venema, Danielle, Boersma, Rinske, Jongen-Lavrencic, Mojca, Fehr, Martin, Hoogendoorn, Mels, Manz, Markus G, Söhne, Maaike, van Marwijk Kooy, Rien, Deeren, Dries, van der Poel, Marjolein W M, Legdeur, Marie Cecile, Tick, Lidwine, Chalandon, Yves, Ammatuna, Emanuele, Blum, Sabine, Löwenberg, Bob, Ossenkoppele, Gert J, and Huls, Gerwin

Subjects
610 Medicine & health
Abstract

Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival.

Published
2023

22. Measurable residual disease-guided therapy in intermediate-risk acute myeloid leukemia patients is a valuable strategy in reducing allogeneic transplantation without negatively affecting survival

Author

Tettero, Jesse M., primary, Ngai, Lok Lam, additional, Bachas, Costa, additional, Breems, Dimitri A., additional, Fischer, Thomas, additional, Gjertsen, Bjorn T., additional, Gradowska, Patrycja, additional, Griskevicius, Laimonas, additional, Janssen, Jeroen J.W.M., additional, Juliusson, Gunnar, additional, Maertens, Johan, additional, Manz, Markus G., additional, Pabst, Thomas, additional, Passweg, Jakob, additional, Porkka, Kimmo, additional, Valk, Peter J.M., additional, Löwenberg, Bob, additional, Ossenkoppele, Gert J., additional, and Cloos, Jacqueline, additional

Published
2023
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23. Measurable residual disease-guided therapy in intermediate-risk acute myeloid leukemia patients is a valuable strategy in reducing allogeneic transplantation without negatively affecting survival

Author

Tettero, Jesse M., Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A., Fischer, Thomas, Gjertsen, Bjorn T., Gradowska, Patrycja, Griskevicius, Laimonas, Janssen, Jeroen J.W.M., Juliusson, Gunnar, Maertens, Johan, Manz, Markus G., Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Valk, Peter J.M., Löwenberg, Bob, Ossenkoppele, Gert J., Cloos, Jacqueline, Tettero, Jesse M., Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A., Fischer, Thomas, Gjertsen, Bjorn T., Gradowska, Patrycja, Griskevicius, Laimonas, Janssen, Jeroen J.W.M., Juliusson, Gunnar, Maertens, Johan, Manz, Markus G., Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Valk, Peter J.M., Löwenberg, Bob, Ossenkoppele, Gert J., and Cloos, Jacqueline

Published
2023

24. Prospective validation of the prognostic relevance of CD34$^{+}$CD38$^{-}$ AML stem cell frequency in the HOVON-SAKK132 trial

Author

Ngai, Lok Lam; https://orcid.org/0000-0003-0969-3766, Hanekamp, Diana; https://orcid.org/0000-0002-5902-1127, Janssen, Fleur, Carbaat-Ham, Jannemieke, Hofland, Maaike A M A, Fayed, Mona M H E, Kelder, Angèle, Oudshoorn-van Marsbergen, Laura, Scholten, Willemijn J, Snel, Alexander N, Bachas, Costa; https://orcid.org/0000-0001-5983-6193, Tettero, Jesse M; https://orcid.org/0000-0002-0811-0824, Breems, Dimitri A, Fischer, Thomas, Gjertsen, Bjørn T; https://orcid.org/0000-0001-9358-9704, Griškevičius, Laimonas; https://orcid.org/0000-0002-3731-1537, Juliusson, Gunnar; https://orcid.org/0000-0002-7911-7265, van de Loosdrecht, Arjan A; https://orcid.org/0000-0001-8311-983X, Maertens, Johan A; https://orcid.org/0000-0003-4257-5980, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Pabst, Thomas; https://orcid.org/0000-0002-6055-5257, Passweg, Jakob R; https://orcid.org/0000-0001-7092-3351, Porkka, Kimmo; https://orcid.org/0000-0003-4112-5902, Valk, Peter J M; https://orcid.org/0000-0002-8857-9461, Gradowska, Patrycja; https://orcid.org/0000-0002-4620-9163, Löwenberg, Bob; https://orcid.org/0000-0001-8982-5217, de Leeuw, David C; https://orcid.org/0000-0003-4591-8467, Janssen, Jeroen J W M, Ossenkoppele, Gert J, Cloos, Jacqueline; https://orcid.org/0000-0001-9150-8026, Ngai, Lok Lam; https://orcid.org/0000-0003-0969-3766, Hanekamp, Diana; https://orcid.org/0000-0002-5902-1127, Janssen, Fleur, Carbaat-Ham, Jannemieke, Hofland, Maaike A M A, Fayed, Mona M H E, Kelder, Angèle, Oudshoorn-van Marsbergen, Laura, Scholten, Willemijn J, Snel, Alexander N, Bachas, Costa; https://orcid.org/0000-0001-5983-6193, Tettero, Jesse M; https://orcid.org/0000-0002-0811-0824, Breems, Dimitri A, Fischer, Thomas, Gjertsen, Bjørn T; https://orcid.org/0000-0001-9358-9704, Griškevičius, Laimonas; https://orcid.org/0000-0002-3731-1537, Juliusson, Gunnar; https://orcid.org/0000-0002-7911-7265, van de Loosdrecht, Arjan A; https://orcid.org/0000-0001-8311-983X, Maertens, Johan A; https://orcid.org/0000-0003-4257-5980, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Pabst, Thomas; https://orcid.org/0000-0002-6055-5257, Passweg, Jakob R; https://orcid.org/0000-0001-7092-3351, Porkka, Kimmo; https://orcid.org/0000-0003-4112-5902, Valk, Peter J M; https://orcid.org/0000-0002-8857-9461, Gradowska, Patrycja; https://orcid.org/0000-0002-4620-9163, Löwenberg, Bob; https://orcid.org/0000-0001-8982-5217, de Leeuw, David C; https://orcid.org/0000-0003-4591-8467, Janssen, Jeroen J W M, Ossenkoppele, Gert J, and Cloos, Jacqueline; https://orcid.org/0000-0001-9150-8026

Published
2023

25. Age and sex associate with outcome in older AML and high risk MDS patients treated with 10-day decitabine

Author

Hilberink, Jacobien R; https://orcid.org/0000-0003-3726-8935, van Zeventer, Isabelle A, Chitu, Dana A, Pabst, Thomas; https://orcid.org/0000-0002-6055-5257, Klein, Saskia K; https://orcid.org/0000-0001-8847-2704, Stussi, Georg; https://orcid.org/0000-0002-1667-0637, Griskevicius, Laimonas, Valk, Peter J M; https://orcid.org/0000-0002-8857-9461, Cloos, Jacqueline, van de Loosdrecht, Arjan A, Breems, Dimitri, van Lammeren-Venema, Danielle, Boersma, Rinske, Jongen-Lavrencic, Mojca, Fehr, Martin, Hoogendoorn, Mels, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Söhne, Maaike, van Marwijk Kooy, Rien, Deeren, Dries, van der Poel, Marjolein W M, Legdeur, Marie Cecile, Tick, Lidwine; https://orcid.org/0000-0002-0771-5231, Chalandon, Yves; https://orcid.org/0000-0001-9341-8104, Ammatuna, Emanuele, Blum, Sabine; https://orcid.org/0000-0003-2275-3081, Löwenberg, Bob; https://orcid.org/0000-0001-8982-5217, Ossenkoppele, Gert J, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), Swiss Group for Clinical Cancer Research (SAKK), et al, Hilberink, Jacobien R; https://orcid.org/0000-0003-3726-8935, van Zeventer, Isabelle A, Chitu, Dana A, Pabst, Thomas; https://orcid.org/0000-0002-6055-5257, Klein, Saskia K; https://orcid.org/0000-0001-8847-2704, Stussi, Georg; https://orcid.org/0000-0002-1667-0637, Griskevicius, Laimonas, Valk, Peter J M; https://orcid.org/0000-0002-8857-9461, Cloos, Jacqueline, van de Loosdrecht, Arjan A, Breems, Dimitri, van Lammeren-Venema, Danielle, Boersma, Rinske, Jongen-Lavrencic, Mojca, Fehr, Martin, Hoogendoorn, Mels, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Söhne, Maaike, van Marwijk Kooy, Rien, Deeren, Dries, van der Poel, Marjolein W M, Legdeur, Marie Cecile, Tick, Lidwine; https://orcid.org/0000-0002-0771-5231, Chalandon, Yves; https://orcid.org/0000-0001-9341-8104, Ammatuna, Emanuele, Blum, Sabine; https://orcid.org/0000-0003-2275-3081, Löwenberg, Bob; https://orcid.org/0000-0001-8982-5217, Ossenkoppele, Gert J, Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), Swiss Group for Clinical Cancer Research (SAKK), and et al

Abstract

Treatment choice according to the individual conditions remains challenging, particularly in older patients with acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS). The impact of performance status, comorbidities, and physical functioning on survival is not well defined for patients treated with hypomethylating agents. Here we describe the impact of performance status (14% ECOG performance status 2), comorbidity (40% HCT-comorbidity index ≥ 2), and physical functioning (41% short physical performance battery < 9 and 17% ADL index < 6) on overall survival (OS) in 115 older patients (age ≥ 66 years) treated on a clinical trial with a 10-day decitabine schedule. None of the patient-related variables showed a significant association with OS. Multivariable analysis revealed that age > 76 years was significantly associated with reduced OS (HR 1.58; p = 0.043) and female sex was associated with superior OS (HR 0.62; p = 0.06). We further compared the genetic profiles of these subgroups. This revealed comparable mutational profiles in patients younger and older than 76 years, but, interestingly, revealed significantly more prevalent mutated ASXL1, STAG2, and U2AF1 in male compared to female patients. In this cohort of older patients treated with decitabine age and sex, but not comorbidities, physical functioning or cytogenetic risk were associated with overall survival.

Published
2023

26. Measurable residual disease-guided therapy in intermediate-risk acute myeloid leukemia patients is a valuable strategy in reducing allogeneic transplantation without negatively affecting survival

Author

Tettero, Jesse M, Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A, Fischer, Thomas, Gjertsen, Bjorn T, Gradowska, Patrycja, Griskevicius, Laimonas, Janssen, Jeroen J W M, Juliusson, Gunnar, Maertens, Johan, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Valk, Peter J M; https://orcid.org/0000-0002-8857-9461, Löwenberg, Bob; https://orcid.org/0000-0001-8982-5217, Ossenkoppele, Gert J, Cloos, Jacqueline, Tettero, Jesse M, Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A, Fischer, Thomas, Gjertsen, Bjorn T, Gradowska, Patrycja, Griskevicius, Laimonas, Janssen, Jeroen J W M, Juliusson, Gunnar, Maertens, Johan, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Valk, Peter J M; https://orcid.org/0000-0002-8857-9461, Löwenberg, Bob; https://orcid.org/0000-0001-8982-5217, Ossenkoppele, Gert J, and Cloos, Jacqueline

Published
2023

28. Prospective Validation of CD34+CD38- Leukemic Stem Cell Frequency in the HOVON-SAKK 132 Trial: Perspectives for Future Improvements

Author

Ngai, Lok Lam, primary, Hanekamp, Diana, additional, Janssen, Fleur, additional, Carbaat-Ham, Jannemieke, additional, Hofland, Maaike A.M., additional, Fayed, Mona M.H.E, additional, Kelder, Angèle, additional, Oudshoorn-van Marsbergen, Laura, additional, Scholten, Willemijn J., additional, Snel, Alexander N., additional, Bachas, Costa, additional, Tettero, Jesse M., additional, Breems, Dimitri A., additional, Fischer, Thomas, additional, Gjertsen, Bjørn Tore, additional, Griškevičius, Laimonas, additional, Juliusson, Gunnar, additional, Maertens, Johan A., additional, Manz, Markus G, additional, Pabst, Thomas, additional, Passweg, Jakob R., additional, Porkka, Kimmo, additional, Gradowska, Patrycja, additional, Lowenberg, Bob, additional, de Leeuw, David C., additional, Janssen, Jeroen J.W.M., additional, Ossenkoppele, Gert J., additional, and Cloos, Jacqueline, additional

Published
2022
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29. Bayesian Inference for Optimization of Interim Analysis in Clinical Trials By Incorporation of Historical Data: Reanalysis of the HOVON AML 132 Clinical Trial

Author

Van Der Maas, Niek, primary, Nasserinejad, Kazem, additional, Pabst, Thomas, additional, Maertens, Johan A., additional, Breems, Dimitri A., additional, Manz, Markus G, additional, Cloos, Jacqueline, additional, Ossenkoppele, Gert J., additional, Floisand, Yngvar, additional, Gradowska, Patrycja, additional, Lowenberg, Bob, additional, Huls, Gerwin A., additional, Postmus, Douwe, additional, Pignatti, Francesco, additional, Cornelissen, Jan J., additional, and Versluis, Jurjen, additional

Published
2022
Full Text
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30. Measurable Residual Disease Guided Therapy in Intermediate-Risk AML Patients Compared to an Unguided Cohort Using Propensity Score Matching

Author

Tettero, Jesse M., primary, Ngai, Lok Lam, additional, Bachas, Costa, additional, Breems, Dimitri A., additional, Fischer, Thomas, additional, Gjertsen, Bjørn Tore, additional, Gradowska, Patrycja, additional, Griskevicius, Laimonas, additional, Janssen, Jeroen J.W.M., additional, Juliusson, Gunnar, additional, Maertens, Johan A., additional, Manz, Markus G, additional, Pabst, Thomas, additional, Passweg, Jakob, additional, Porkka, Kimmo, additional, Valk, Peter JM, additional, Lowenberg, Bob, additional, Ossenkoppele, Gert J., additional, and Cloos, Jacqueline, additional

Published
2022
Full Text
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31. Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis

Author

Tettero, Jesse M., primary, Al-Badri, Waleed K. W., additional, Ngai, Lok Lam, additional, Bachas, Costa, additional, Breems, Dimitri A., additional, van Elssen, Catharina H. M. J., additional, Fischer, Thomas, additional, Gjertsen, Bjorn T., additional, van Gorkom, Gwendolyn N. Y., additional, Gradowska, Patrycja, additional, Greuter, Marjolein J. E., additional, Griskevicius, Laimonas, additional, Juliusson, Gunnar, additional, Maertens, Johan, additional, Manz, Markus G., additional, Pabst, Thomas, additional, Passweg, Jakob, additional, Porkka, Kimmo, additional, Löwenberg, Bob, additional, Ossenkoppele, Gert J., additional, Janssen, Jeroen J. W. M., additional, and Cloos, Jacqueline, additional

Published
2022
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32. Adequate iron chelation therapy for at least six months improves survival in transfusion-dependent patients with lower risk myelodysplastic syndromes

Author

Delforge, Michel, Selleslag, Dominik, Beguin, Yves, Triffet, Agnès, Mineur, Philippe, Theunissen, Koen, Graux, Carlos, Trullemans, Fabienne, Boulet, Dominique, Van Eygen, Koen, Noens, Lucien, Van Steenweghen, Steven, Lemmens, Jan, Pierre, Pascal, D’hondt, Randal, Ferrant, Augustin, Deeren, Dries, Van De Velde, Ann, Wynendaele, Wim, André, Marc, De Bock, Robrecht, Efira, André, Breems, Dimitri, Deweweire, Anne, Geldhof, Kurt, Pluymers, Wim, Harrington, Amanda, MacDonald, Karen, Abraham, Ivo, and Ravoet, Christophe

Published
2014
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33. Clofarabine added to intensive treatment in adult patients with newly diagnosed ALL: the HOVON-100 trial.

Author

UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - (SLuc) Service d'hématologie, Rijneveld, Anita W, van der Holt, Bronno, de Weerdt, Okke, Biemond, Bart J, van de Loosdrecht, Arjen A, van der Wagen, Lotte E, Bellido, Mar, van Gelder, Michel, van der Velden, Walter J F M, Selleslag, Dominik, van Lammeren-Venema, Daniëlle, Halkes, Constantijn J M, Fijnheer, Rob, Havelange, Violaine, van Sluis, Geerte L, Legdeur, Marie-Cecile, Deeren, Dries, Gadisseur, Alain, Sinnige, Harm A M, Breems, Dimitri A, Jaspers, Aurélie, Legrand, Ollivier, Terpstra, Wim E, Boersma, Rinske S, Mazure, Dominiek, Triffet, Agnes, Tick, Lidwine W, Beel, Karolien, Maertens, Johan A, Beverloo, H Berna, Bakkus, Marleen, Homburg, Christa H E, de Haas, Valerie, van der Velden, Vincent H J, Cornelissen, Jan J, Dutch-Belgian HOVON Cooperative group, UCL - SSS/DDUV/MEXP - Médecine expérimentale, UCL - (SLuc) Service d'hématologie, Rijneveld, Anita W, van der Holt, Bronno, de Weerdt, Okke, Biemond, Bart J, van de Loosdrecht, Arjen A, van der Wagen, Lotte E, Bellido, Mar, van Gelder, Michel, van der Velden, Walter J F M, Selleslag, Dominik, van Lammeren-Venema, Daniëlle, Halkes, Constantijn J M, Fijnheer, Rob, Havelange, Violaine, van Sluis, Geerte L, Legdeur, Marie-Cecile, Deeren, Dries, Gadisseur, Alain, Sinnige, Harm A M, Breems, Dimitri A, Jaspers, Aurélie, Legrand, Ollivier, Terpstra, Wim E, Boersma, Rinske S, Mazure, Dominiek, Triffet, Agnes, Tick, Lidwine W, Beel, Karolien, Maertens, Johan A, Beverloo, H Berna, Bakkus, Marleen, Homburg, Christa H E, de Haas, Valerie, van der Velden, Vincent H J, Cornelissen, Jan J, and Dutch-Belgian HOVON Cooperative group

Abstract

Clofarabine (CLO) is a nucleoside analog with efficacy in relapsed/refractory acute lymphoblastic leukemia (ALL). This randomized phase 3 study aimed to evaluate whether CLO added to induction and whether consolidation would improve outcome in adults with newly diagnosed ALL. Treatment of younger (18-40 years) patients consisted of a pediatric-inspired protocol, and for older patients (41-70 years), a semi-intensive protocol was used. Three hundred and forty patients were randomized. After a median follow-up of 70 months, 5-year event-free survival (EFS) was 50% and 53% for arm A and B (CLO arm). For patients ≤40 years, EFS was 58% vs 65% in arm A vs B, whereas in patients >40 years, EFS was 43% in both arms. Complete remission (CR) rate was 89% in both arms and similar in younger and older patients. Minimal residual disease (MRD) was assessed in 200 patients (60%). Fifty-four of 76 evaluable patients (71%) were MRD- after consolidation 1 in arm A vs 75/81 (93%) in arm B (P = .001). Seventy (42%) patients proceeded to allogeneic hematopoietic stem cell transplantation in both arms. Five-year overall survival (OS) was similar in both arms: 60% vs 61%. Among patients achieving CR, relapse rates were 28% and 24%, and nonrelapse mortality was 16% vs 17% after CR. CLO-treated patients experienced more serious adverse events, more infections, and more often went off protocol. This was most pronounced in older patients. We conclude that, despite a higher rate of MRD negativity, addition of CLO does not improve outcome in adults with ALL, which might be due to increased toxicity. This trial was registered at www.trialregister.nl as #NTR2004.

Published
2022

34. Clofarabine added to intensive treatment in adult patients with newly diagnosed ALL:the HOVON-100 trial

Author

Rijneveld, Anita W., van der Holt, Bronno, de Weerdt, Okke, Biemond, Bart J., van de Loosdrecht, Arjen A., van der Wagen, Lotte E., Bellido, Mar, van Gelder, Michel, van der Velden, Walter J.F.M., Selleslag, Dominik, van Lammeren-Venema, Danie€lle, Halkes, Constantijn J.M., Fijnheer, Rob, Havelange, Violaine, van Sluis, Geerte L., Legdeur, Marie Cecile, Deeren, Dries, Gadisseur, Alain, Sinnige, Harm A.M., Breems, Dimitri A., Jaspers, Aurelie, Legrand, Ollivier, Terpstra, Wim E., Boersma, Rinske S., Mazure, Dominiek, Triffet, Agnes, Tick, Lidwine W., Beel, Karolien, Maertens, Johan A., Beverloo, H. Berna, Bakkus, Marleen, Homburg, Christa H.E., de Haas, Valerie, van der Velden, Vincent H.J., Cornelissen, Jan J., Rijneveld, Anita W., van der Holt, Bronno, de Weerdt, Okke, Biemond, Bart J., van de Loosdrecht, Arjen A., van der Wagen, Lotte E., Bellido, Mar, van Gelder, Michel, van der Velden, Walter J.F.M., Selleslag, Dominik, van Lammeren-Venema, Danie€lle, Halkes, Constantijn J.M., Fijnheer, Rob, Havelange, Violaine, van Sluis, Geerte L., Legdeur, Marie Cecile, Deeren, Dries, Gadisseur, Alain, Sinnige, Harm A.M., Breems, Dimitri A., Jaspers, Aurelie, Legrand, Ollivier, Terpstra, Wim E., Boersma, Rinske S., Mazure, Dominiek, Triffet, Agnes, Tick, Lidwine W., Beel, Karolien, Maertens, Johan A., Beverloo, H. Berna, Bakkus, Marleen, Homburg, Christa H.E., de Haas, Valerie, van der Velden, Vincent H.J., and Cornelissen, Jan J.

Abstract

Clofarabine (CLO) is a nucleoside analog with efficacy in relapsed/refractory acute lymphoblastic leukemia (ALL). This randomized phase 3 study aimed to evaluate whether CLO added to induction and whether consolidation would improve outcome in adults with newly diagnosed ALL. Treatment of younger (18-40 years) patients consisted of a pediatric-inspired protocol, and for older patients (41-70 years), a semi-intensive protocol was used. Three hundred and forty patients were randomized. After a median follow-up of 70 months, 5-year event-free survival (EFS) was 50% and 53% for arm A and B (CLO arm). For patients #40 years, EFS was 58% vs 65% in arm A vs B, whereas in patients .40 years, EFS was 43% in both arms. Complete remission (CR) rate was 89% in both arms and similar in younger and older patients. Minimal residual disease (MRD) was assessed in 200 patients (60%). Fifty-four of 76 evaluable patients (71%) were MRD2 after consolidation 1 in arm A vs 75/81 (93%) in arm B (P 5 .001). Seventy (42%) patients proceeded to allogeneic hematopoietic stem cell transplantation in both arms. Five-year overall survival (OS) was similar in both arms: 60% vs 61%. Among patients achieving CR, relapse rates were 28% and 24%, and nonrelapse mortality was 16% vs 17% after CR. CLO-treated patients experienced more serious adverse events, more infections, and more often went off protocol. This was most pronounced in older patients. We conclude that, despite a higher rate of MRD negativity, addition of CLO does not improve outcome in adults with ALL, which might be due to increased toxicity.

Published
2022

35. The added value of multi-state modelling in a randomized controlled trial:The HOVON 102 study re-analyzed

Author

Bakunina, Katerina, Putter, Hein, Versluis, Jurjen, Koster, Eva A.S., van der Holt, Bronno, Manz, Markus G., Breems, Dimitri A., Gjertsen, Bjorn T., Cloos, Jacqueline, Valk, Peter J.M., Passweg, Jakob, Pabst, Thomas, Ossenkoppele, Gert J., Löwenberg, Bob, Cornelissen, Jan J., de Wreede, Liesbeth C., Bakunina, Katerina, Putter, Hein, Versluis, Jurjen, Koster, Eva A.S., van der Holt, Bronno, Manz, Markus G., Breems, Dimitri A., Gjertsen, Bjorn T., Cloos, Jacqueline, Valk, Peter J.M., Passweg, Jakob, Pabst, Thomas, Ossenkoppele, Gert J., Löwenberg, Bob, Cornelissen, Jan J., and de Wreede, Liesbeth C.

Abstract

Clofarabine is an active antileukemic drug for subgroups of patients with acute myeloid leukemia (AML). Multi-state models can provide additional insights to supplement the original intention-to-treat analysis of randomized controlled trials (RCT). We re-analyzed the HOVON102/SAKK30/09 phase III RCT for newly diagnosed AML patients, which randomized between standard induction chemotherapy with or without clofarabine. Using multi-state models, we evaluated the effects of induction chemotherapy outcomes (complete remission [CR], measurable residual disease [MRD]), and post-remission therapy with allogeneic stem cell transplantation [alloSCT] on relapse and death. Through the latter a consistent reduction in the hazard of relapse in the clofarabine arm compared to the standard arm was found, which occurred irrespective of MRD status or post-remission treatment with alloSCT, demonstrating a strong and persistent antileukemic effect of clofarabine. During the time period between achieving CR and possible post-remission treatment with alloSCT, non-relapse mortality was higher in patients receiving clofarabine. An overall net benefit of treatment with clofarabine was identified using the composite endpoint current leukemia-free survival (CLFS). In conclusion, these results enforce and extend the earlier reported beneficial effect of clofarabine in AML and show that multi-state models further detail the effect of treatment on competing and series of events.

Published
2022

36. Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia:An outcome- and cost-analysis

Author

Tettero, Jesse M., Al-Badri, Waleed K.W., Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A., van Elssen, Catharina H.M.J., Fischer, Thomas, Gjertsen, Bjorn T., van Gorkom, Gwendolyn N.Y., Gradowska, Patrycja, Greuter, Marjolein J.E., Griskevicius, Laimonas, Juliusson, Gunnar, Maertens, Johan, Manz, Markus G., Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Löwenberg, Bob, Ossenkoppele, Gert J., Janssen, Jeroen J.W.M., Cloos, Jacqueline, Tettero, Jesse M., Al-Badri, Waleed K.W., Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A., van Elssen, Catharina H.M.J., Fischer, Thomas, Gjertsen, Bjorn T., van Gorkom, Gwendolyn N.Y., Gradowska, Patrycja, Greuter, Marjolein J.E., Griskevicius, Laimonas, Juliusson, Gunnar, Maertens, Johan, Manz, Markus G., Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Löwenberg, Bob, Ossenkoppele, Gert J., Janssen, Jeroen J.W.M., and Cloos, Jacqueline

Abstract

Measurable residual disease (MRD) measured using multiparameter flow-cytometry (MFC) has proven to be an important prognostic biomarker in acute myeloid leukemia (AML). In addition, MRD is increasingly used to guide consolidation treatment towards a non-allogenic stem cell transplantation treatment for MRD-negative patients in the ELN-2017 intermediate risk group. Currently, measurement of MFC-MRD in bone marrow is used for clinical decision making after 2 cycles of induction chemotherapy. However, measurement after 1 cycle has also been shown to have prognostic value, so the optimal time point remains a question of debate. We assessed the independent prognostic value of MRD results at either time point and concordance between these for 273 AML patients treated within and according to the HOVON-SAKK 92, 102, 103 and 132 trials. Cumulative incidence of relapse, event free survival and overall survival were significantly better for MRD-negative (<0.1%) patients compared to MRD-positive patients after cycle 1 and cycle 2 (p ≤ 0.002, for all comparisons). A total of 196 patients (71.8%) were MRD-negative after cycle 1, of which the vast majority remained negative after cycle 2 (180 patients; 91.8%). In contrast, of the 77 MRD-positive patients after cycle 1, only 41 patients (53.2%) remained positive. A cost reduction of –€571,751 per 100 patients could be achieved by initiating the donor search based on the MRD-result after cycle 1. This equals to a 50.7% cost reduction compared to the current care strategy in which the donor search is initiated for all patients. These results show that MRD after cycle 1 has prognostic value and is highly concordant with MRD status after cycle 2. When MRD-MFC is used to guide consolidation treatment (allo vs non-allo) in intermediate risk patients, allogeneic donor search may be postponed or omitted after cycle 1. Since the majority of MRD-negative patients remain negative after cycle 2, this could safely reduce the number of all

Published
2022

37. Concordance in measurable residual disease result after first and second induction cycle in acute myeloid leukemia: An outcome- and cost-analysis

Author

Tettero, Jesse M, Al-Badri, Waleed K W, Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A, van Elssen, Catharina H M J, Fischer, Thomas, Gjertsen, Bjorn T, van Gorkom, Gwendolyn N Y, Gradowska, Patrycja, Greuter, Marjolein J E, Griskevicius, Laimonas, Juliusson, Gunnar, Maertens, Johan, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Löwenberg, Bob, Ossenkoppele, Gert J, Janssen, Jeroen J W M, Cloos, Jacqueline, Tettero, Jesse M, Al-Badri, Waleed K W, Ngai, Lok Lam, Bachas, Costa, Breems, Dimitri A, van Elssen, Catharina H M J, Fischer, Thomas, Gjertsen, Bjorn T, van Gorkom, Gwendolyn N Y, Gradowska, Patrycja, Greuter, Marjolein J E, Griskevicius, Laimonas, Juliusson, Gunnar, Maertens, Johan, Manz, Markus G; https://orcid.org/0000-0002-4676-7931, Pabst, Thomas, Passweg, Jakob, Porkka, Kimmo, Löwenberg, Bob, Ossenkoppele, Gert J, Janssen, Jeroen J W M, and Cloos, Jacqueline

Abstract

Measurable residual disease (MRD) measured using multiparameter flow-cytometry (MFC) has proven to be an important prognostic biomarker in acute myeloid leukemia (AML). In addition, MRD is increasingly used to guide consolidation treatment towards a non-allogenic stem cell transplantation treatment for MRD-negative patients in the ELN-2017 intermediate risk group. Currently, measurement of MFC-MRD in bone marrow is used for clinical decision making after 2 cycles of induction chemotherapy. However, measurement after 1 cycle has also been shown to have prognostic value, so the optimal time point remains a question of debate. We assessed the independent prognostic value of MRD results at either time point and concordance between these for 273 AML patients treated within and according to the HOVON-SAKK 92, 102, 103 and 132 trials. Cumulative incidence of relapse, event free survival and overall survival were significantly better for MRD-negative (<0.1%) patients compared to MRD-positive patients after cycle 1 and cycle 2 (p ≤ 0.002, for all comparisons). A total of 196 patients (71.8%) were MRD-negative after cycle 1, of which the vast majority remained negative after cycle 2 (180 patients; 91.8%). In contrast, of the 77 MRD-positive patients after cycle 1, only 41 patients (53.2%) remained positive. A cost reduction of -€571,751 per 100 patients could be achieved by initiating the donor search based on the MRD-result after cycle 1. This equals to a 50.7% cost reduction compared to the current care strategy in which the donor search is initiated for all patients. These results show that MRD after cycle 1 has prognostic value and is highly concordant with MRD status after cycle 2. When MRD-MFC is used to guide consolidation treatment (allo vs non-allo) in intermediate risk patients, allogeneic donor search may be postponed or omitted after cycle 1. Since the majority of MRD-negative patients remain negative after cycle 2, this could safely reduce the number of allogenei

Published
2022

38. The added value of multi-state modelling in a randomized controlled trial: The HOVON 102 study re-analyzed

Author

Bakunina, Katerina; https://orcid.org/0000-0003-3737-7971, Putter, Hein, Versluis, Jurjen, Koster, Eva A S; https://orcid.org/0000-0002-8446-5133, van der Holt, Bronno, Manz, Markus G, Breems, Dimitri A, Gjertsen, Bjorn T, Cloos, Jacqueline, Valk, Peter J M, Passweg, Jakob, Pabst, Thomas, Ossenkoppele, Gert J, Löwenberg, Bob, Cornelissen, Jan J, de Wreede, Liesbeth C, Bakunina, Katerina; https://orcid.org/0000-0003-3737-7971, Putter, Hein, Versluis, Jurjen, Koster, Eva A S; https://orcid.org/0000-0002-8446-5133, van der Holt, Bronno, Manz, Markus G, Breems, Dimitri A, Gjertsen, Bjorn T, Cloos, Jacqueline, Valk, Peter J M, Passweg, Jakob, Pabst, Thomas, Ossenkoppele, Gert J, Löwenberg, Bob, Cornelissen, Jan J, and de Wreede, Liesbeth C

Abstract

Clofarabine is an active antileukemic drug for subgroups of patients with acute myeloid leukemia (AML). Multi-state models can provide additional insights to supplement the original intention-to-treat analysis of randomized controlled trials (RCT). We re-analyzed the HOVON102/SAKK30/09 phase III RCT for newly diagnosed AML patients, which randomized between standard induction chemotherapy with or without clofarabine. Using multi-state models, we evaluated the effects of induction chemotherapy outcomes (complete remission [CR], measurable residual disease [MRD]), and post-remission therapy with allogeneic stem cell transplantation [alloSCT] on relapse and death. Through the latter a consistent reduction in the hazard of relapse in the clofarabine arm compared to the standard arm was found, which occurred irrespective of MRD status or post-remission treatment with alloSCT, demonstrating a strong and persistent antileukemic effect of clofarabine. During the time period between achieving CR and possible post-remission treatment with alloSCT, non-relapse mortality was higher in patients receiving clofarabine. An overall net benefit of treatment with clofarabine was identified using the composite endpoint current leukemia-free survival (CLFS). In conclusion, these results enforce and extend the earlier reported beneficial effect of clofarabine in AML and show that multi-state models further detail the effect of treatment on competing and series of events.

Published
2022

39. Addition of bevacizumab to chemotherapy in acute myeloid leukemia at older age: a randomized phase 2 trial of the Dutch-Belgian Cooperative Trial Group for Hemato-Oncology (HOVON) and the Swiss Group for Clinical Cancer Research (SAKK)

Author

Ossenkoppele, Gert J., Stussi, Georg, Maertens, Johan, van Montfort, Kees, Biemond, Bart J., Breems, Dimitri, Ferrant, August, Graux, Carlos, de Greef, Georgine E., Halkes, C. J.M., Hoogendoorn, Mels, Hollestein, Rene M., Jongen-Lavrencic, Mojca, Levin, Mark D., van de Loosdrecht, Arjan A., van Marwijk Kooij, Marinus, van Norden, Yvette, Pabst, Thomas, Schouten, Harry C., Vellenga, Edo, Verhoef, Gregor E.G., de Weerdt, Okke, Wijermans, Pierre, Passweg, Jakob R., and Löwenberg, Bob

Published
2012
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40. Viral Evolution and Immunology of SARS-CoV-2 in a Persistent Infection after Treatment with Rituximab

Author

Van der Moeren, Nathalie, primary, Selhorst, Philippe, additional, Ha, My, additional, Heireman, Laura, additional, Van Gaal, Pieter-Jan, additional, Breems, Dimitri, additional, Meysman, Pieter, additional, Laukens, Kris, additional, Verstrepen, Walter, additional, Van Gasse, Natasja, additional, Ogunjimi, Benson, additional, Arien, Kevin K., additional, and Naesens, Reinout, additional

Published
2022
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41. The added value of multi‐state modelling in a randomized controlled trial: The HOVON 102 study re‐analyzed

Author

Bakunina, Katerina, primary, Putter, Hein, additional, Versluis, Jurjen, additional, Koster, Eva A. S., additional, van der Holt, Bronno, additional, Manz, Markus G., additional, Breems, Dimitri A., additional, Gjertsen, Bjorn T., additional, Cloos, Jacqueline, additional, Valk, Peter J. M., additional, Passweg, Jakob, additional, Pabst, Thomas, additional, Ossenkoppele, Gert J., additional, Löwenberg, Bob, additional, Cornelissen, Jan J., additional, and de Wreede, Liesbeth C., additional

Published
2021
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42. Gemtuzumab ozogamicin as postremission treatment in AML at 60 years of age or more: results of a multicenter phase 3 study

Author

Löwenberg, Bob, Beck, Joachim, Graux, Carlos, van Putten, Wim, Schouten, Harry C., Verdonck, Leo F., Ferrant, Augustin, Sonneveld, Pieter, Jongen-Lavrencic, Mojca, von Lilienfeld-Toal, Marie, Biemond, Bart J., Vellenga, Edo, Breems, Dimitri, de Muijnck, Hilde, Schaafsma, Ron, Verhoef, Gregor, Döhner, Hartmut, Gratwohl, Alois, Pabst, Thomas, Ossenkoppele, Gert J., Maertens, Johan, for the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON), German Austrian AML Study Group (AMLSG), and Swiss Group for Clinical Cancer Research Collaborative Group (SAKK)

Published
2010
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43. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, Ossenkoppele, Gert J, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - SSS/IREC/SLUC - Pôle St.-Luc, UCL - (MGD) Service d'hématologie, UCL - (SLuc) Service d'hématologie, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, and Ossenkoppele, Gert J

Abstract

Lenalidomide, an antineoplastic and immunomodulatory drug, has therapeutic activity in acute myeloid leukemia (AML), but definitive studies about its therapeutic utility have been lacking. In a phase 3 study, we compared 2 induction regimens in newly diagnosed patients age 18 to 65 years with AML: idarubicine-cytarabine (cycle 1) and daunorubicin and intermediate-dose cytarabine (cycle 2) without or with lenalidomide (15 mg orally on days 1-21). One final consolidation cycle of chemotherapy or autologous stem cell transplantation (auto-SCT) or allogeneic SCT (allo-SCT) was provided according to a prognostic risk and minimal residual disease (MRD)-adapted approach. Event-free survival (EFS; primary end point) and other clinical end points were assessed. A second random assignment in patients in complete response or in complete response with incomplete hematologic recovery after cycle 3 or auto-SCT involved 6 cycles of maintenance with lenalidomide (10 mg on days 1-21) or observation. In all, 392 patients were randomly assigned to the control group, and 388 patients were randomly assigned to lenalidomide induction. At a median follow-up of 41 months, the study revealed no differences in outcome between the treatments (EFS, 44% ± 2% standard error and overall survival, 54% ± 2% at 4 years for both arms) although in an exploratory post hoc analysis, a lenalidomide benefit was suggested in SRSF2-mutant AML. In relation to the previous Dutch-Belgian Hemato-Oncology Cooperative Group and Swiss Group for Clinical Cancer Research (HOVON-SAKK) studies that used a similar 3-cycle regimen but did not pursue an MRD-guided approach, these survival estimates compare markedly more favorably. MRD status after cycle 2 lost prognostic value in intermediate-risk AML in the risk-adjusted treatment context. Maintenance with lenalidomide showed no apparent effect on relapse probability in 88 patients randomly assigned for this part of the study.

Published
2021

44. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS

Author

UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre du cancer, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Janssen, Jeroen, Löwenberg, Bob, Manz, Markus, Bargetzi, Mario, Biemond, Bart, Borne, Peter von dem, Breems, Dimitri, Brouwer, Rolf, Chalandon, Yves, Deeren, Dries, Efthymiou, Anna, Gjertsen, Bjørn-Tore, Graux, Carlos, Gregor, Michael, Heim, Dominik, Hess, Urs, Hoogendoorn, Mels, Jaspers, Aurelie, Jie, Asiong, Jongen-Lavrencic, Mojca, Klein, Saskia, Klift, Marjolein van der, Kuball, Jürgen, Lammeren-Venema, Danielle van, Legdeur, Marie-Cecile, Loosdrecht, Arjan van de, Maertens, Johan, Kooy, Marinus van Marwijk, Moors, Ine, Nijziel, Marten, Obbergh, Florence van, Oosterveld, Margriet, Pabst, Thomas, Poel, Marjolein van der, Sinnige, Harm, Spertini, Olivier, Terpstra, Wim, Tick, Lidwine, Velden, Walter van der, Vekemans, Marie-Christiane, Vellenga, Edo, Weerdt, Okke de, Westerweel, Peter, Stüssi, Georg, Norden, Yvette van, Ossenkoppele, Gert, UCL - (SLuc) Service d'hématologie, UCL - (SLuc) Centre du cancer, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Janssen, Jeroen, Löwenberg, Bob, Manz, Markus, Bargetzi, Mario, Biemond, Bart, Borne, Peter von dem, Breems, Dimitri, Brouwer, Rolf, Chalandon, Yves, Deeren, Dries, Efthymiou, Anna, Gjertsen, Bjørn-Tore, Graux, Carlos, Gregor, Michael, Heim, Dominik, Hess, Urs, Hoogendoorn, Mels, Jaspers, Aurelie, Jie, Asiong, Jongen-Lavrencic, Mojca, Klein, Saskia, Klift, Marjolein van der, Kuball, Jürgen, Lammeren-Venema, Danielle van, Legdeur, Marie-Cecile, Loosdrecht, Arjan van de, Maertens, Johan, Kooy, Marinus van Marwijk, Moors, Ine, Nijziel, Marten, Obbergh, Florence van, Oosterveld, Margriet, Pabst, Thomas, Poel, Marjolein van der, Sinnige, Harm, Spertini, Olivier, Terpstra, Wim, Tick, Lidwine, Velden, Walter van der, Vekemans, Marie-Christiane, Vellenga, Edo, Weerdt, Okke de, Westerweel, Peter, Stüssi, Georg, Norden, Yvette van, and Ossenkoppele, Gert

Abstract

Treatment results of AML in elderly patients are unsatisfactory. We hypothesized that addition of tosedostat, an aminopeptidase inhibitor, to intensive chemotherapy may improve outcome in this population. After establishing a safe dose in a run-in phase of the study in 22 patients, 231 eligible patients with AML above 65 years of age (median 70, range 66-81) were randomly assigned in this open label randomized Phase II study to receive standard chemotherapy (3+7) with or without tosedostat at the selected daily dose of 120 mg (n = 116), days 1-21. In the second cycle, patients received cytarabine 1000 mg/m2 twice daily on days 1-6 with or without tosedostat. CR/CRi rates in the 2 arms were not significantly different (69% (95% C.I. 60-77%) vs 64% (55-73%), respectively). At 24 months, event-free survival (EFS) was 20% for the standard arm versus 12% for the tosedostat arm (Cox-p = 0.01) and overall survival (OS) 33% vs 18% respectively (p = 0.006). Infectious complications accounted for an increased early death rate in the tosedostat arm. Atrial fibrillation was more common in the tosedostat arm as well. The results of the present study show that the addition of tosedostat to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients.

Published
2021

45. Addition of lenalidomide to intensive treatment in younger and middle-aged adults with newly diagnosed AML: the HOVON-SAKK-132 trial

Author

CTI Kuball, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, Ossenkoppele, Gert J, CTI Kuball, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Löwenberg, Bob, Pabst, Thomas, Maertens, Johan, Gradowska, Patrycja, Biemond, Bart J, Spertini, Olivier, Vellenga, Edo, Griskevicius, Laimonas, Tick, Lidwine W, Jongen-Lavrencic, Mojca, van Marwijk Kooy, Marinus, Vekemans, Marie-Christiane, van der Velden, Walter J F M, Beverloo, Berna, Michaux, Lucienne, Graux, Carlos, Deeren, Dries, de Weerdt, Okke, van Esser, Joost W J, Bargetzi, Mario, Klein, Saskia K, Gadisseur, Alain, Westerweel, Peter E, Veelken, Hendrik, Gregor, Michael, Silzle, Tobias, van Lammeren-Venema, Daniëlle, Moors, Ine, Breems, Dimitri A, Hoogendoorn, Mels, Legdeur, Marie-Cecile J C, Fischer, Thomas, Kuball, Juergen, Cornelissen, Jan, Porkka, Kimmo, Juliusson, Gunnar, Meyer, Peter, Höglund, Martin, Gjertsen, Bjorn T, Janssen, Jeroen J W M, Huls, Gerwin, Passweg, Jakob, Cloos, Jacqueline, Valk, Peter J M, van Elssen, Catharina H M J, Manz, Markus G, Floisand, Yngvar, and Ossenkoppele, Gert J

Published
2021

46. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS

Author

CTI Kuball, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Janssen, Jeroen, Löwenberg, Bob, Manz, Markus, Bargetzi, Mario, Biemond, Bart, Borne, Peter von dem, Breems, Dimitri, Brouwer, Rolf, Chalandon, Yves, Deeren, Dries, Efthymiou, Anna, Gjertsen, Bjørn-Tore, Graux, Carlos, Gregor, Michael, Heim, Dominik, Hess, Urs, Hoogendoorn, Mels, Jaspers, Aurelie, Jie, Asiong, Jongen-Lavrencic, Mojca, Klein, Saskia, Klift, Marjolein van der, Kuball, Jürgen, Lammeren-Venema, Danielle van, Legdeur, Marie-Cecile, Loosdrecht, Arjan van de, Maertens, Johan, Kooy, Marinus van Marwijk, Moors, Ine, Nijziel, Marten, Obbergh, Florence van, Oosterveld, Margriet, Pabst, Thomas, Poel, Marjolein van der, Sinnige, Harm, Spertini, Olivier, Terpstra, Wim, Tick, Lidwine, Velden, Walter van der, Vekemans, Marie-Christiane, Vellenga, Edo, Weerdt, Okke de, Westerweel, Peter, Stüssi, Georg, Norden, Yvette van, Ossenkoppele, Gert, CTI Kuball, MS Hematologie, Infection & Immunity, Regenerative Medicine and Stem Cells, Cancer, Janssen, Jeroen, Löwenberg, Bob, Manz, Markus, Bargetzi, Mario, Biemond, Bart, Borne, Peter von dem, Breems, Dimitri, Brouwer, Rolf, Chalandon, Yves, Deeren, Dries, Efthymiou, Anna, Gjertsen, Bjørn-Tore, Graux, Carlos, Gregor, Michael, Heim, Dominik, Hess, Urs, Hoogendoorn, Mels, Jaspers, Aurelie, Jie, Asiong, Jongen-Lavrencic, Mojca, Klein, Saskia, Klift, Marjolein van der, Kuball, Jürgen, Lammeren-Venema, Danielle van, Legdeur, Marie-Cecile, Loosdrecht, Arjan van de, Maertens, Johan, Kooy, Marinus van Marwijk, Moors, Ine, Nijziel, Marten, Obbergh, Florence van, Oosterveld, Margriet, Pabst, Thomas, Poel, Marjolein van der, Sinnige, Harm, Spertini, Olivier, Terpstra, Wim, Tick, Lidwine, Velden, Walter van der, Vekemans, Marie-Christiane, Vellenga, Edo, Weerdt, Okke de, Westerweel, Peter, Stüssi, Georg, Norden, Yvette van, and Ossenkoppele, Gert

Published
2021

47. A phase 2, randomized, double-blind, multicenter study comparing siltuximab plus best supportive care (BSC) with placebo plus BSC in anemic patients with International Prognostic Scoring System low- or intermediate-1–risk myelodysplastic syndrome

Author

Garcia-Manero, Guillermo, Gartenberg, Gary, Steensma, David P., Schipperus, Martin R., Breems, Dimitri A., de Paz, Raquel, Valcárcel, David, Kranenburg, Britte, Reddy, Manjula, and Komrokji, Rami S.

Published
2014
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48. Inferior Outcome of Addition of the Aminopeptidase Inhibitor Tosedostat to Standard Intensive Treatment for Elderly Patients with AML and High Risk MDS

Author

Janssen, Jeroen, primary, Löwenberg, Bob, additional, Manz, Markus, additional, Bargetzi, Mario, additional, Biemond, Bart, additional, Borne, Peter von dem, additional, Breems, Dimitri, additional, Brouwer, Rolf, additional, Chalandon, Yves, additional, Deeren, Dries, additional, Efthymiou, Anna, additional, Gjertsen, Bjørn-Tore, additional, Graux, Carlos, additional, Gregor, Michael, additional, Heim, Dominik, additional, Hess, Urs, additional, Hoogendoorn, Mels, additional, Jaspers, Aurelie, additional, Jie, Asiong, additional, Jongen-Lavrencic, Mojca, additional, Klein, Saskia, additional, Klift, Marjolein van der, additional, Kuball, Jürgen, additional, Lammeren-Venema, Danielle van, additional, Legdeur, Marie-Cecile, additional, Loosdrecht, Arjan van de, additional, Maertens, Johan, additional, Kooy, Marinus van Marwijk, additional, Moors, Ine, additional, Nijziel, Marten, additional, Obbergh, Florence van, additional, Oosterveld, Margriet, additional, Pabst, Thomas, additional, Poel, Marjolein van der, additional, Sinnige, Harm, additional, Spertini, Olivier, additional, Terpstra, Wim, additional, Tick, Lidwine, additional, Velden, Walter van der, additional, Vekemans, Marie-Christiane, additional, Vellenga, Edo, additional, Weerdt, Okke de, additional, Westerweel, Peter, additional, Stüssi, Georg, additional, Norden, Yvette van, additional, and Ossenkoppele, Gert, additional

Published
2021
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49. Ibrutinib added to 10-day decitabine for older patients with AML and higher risk MDS

Author

Huls, Gerwin, Chitu, Dana A, Pabst, Thomas, Klein, Saskia K, Stussi, Georg, Griskevicius, Laimonas, Valk, Peter J M, Cloos, Jacqueline, van de Loosdrecht, Arjan A, Breems, Dimitri, van Lammeren-Venema, Danielle, van Zeventer, Isabelle, Boersma, Rinske, Jongen-Lavrencic, Mojca, Fehr, Martin, Hoogendoorn, Mels, Manz, Markus G, Söhne, Maaike, van Marwijk Kooy, Rien, Deeren, Dries, van der Poel, Marjolein W M, Legdeur, Marie Cecile, Tick, Lidwine, Chalandon, Yves, Ammatuna, Emanuele, Blum, Sabine, Löwenberg, Bob, Ossenkoppele, Gert J, Huls, Gerwin, Chitu, Dana A, Pabst, Thomas, Klein, Saskia K, Stussi, Georg, Griskevicius, Laimonas, Valk, Peter J M, Cloos, Jacqueline, van de Loosdrecht, Arjan A, Breems, Dimitri, van Lammeren-Venema, Danielle, van Zeventer, Isabelle, Boersma, Rinske, Jongen-Lavrencic, Mojca, Fehr, Martin, Hoogendoorn, Mels, Manz, Markus G, Söhne, Maaike, van Marwijk Kooy, Rien, Deeren, Dries, van der Poel, Marjolein W M, Legdeur, Marie Cecile, Tick, Lidwine, Chalandon, Yves, Ammatuna, Emanuele, Blum, Sabine, Löwenberg, Bob, and Ossenkoppele, Gert J

Abstract

The treatment of older, unfit patients with acute myeloid leukemia (AML) is challenging. Based on preclinical data of Bruton tyrosine kinase expression/phosphorylation and ibrutinib cytotoxicity in AML blasts, we conducted a randomized phase 2 multicenter study to assess the tolerability and efficacy of the addition of ibrutinib to 10-day decitabine in unfit (ie, Hematopoietic Cell Transplantation Comorbidity Index ≥3) AML patients and higher risk myelodysplasia patients (HOVON135/SAKK30/15 trial). In total, 144 eligible patients were randomly (1:1) assigned to either 10-day decitabine combined with ibrutinib (560 mg; sequentially given, starting the day after the last dose of decitabine) (n = 72) or to 10-day decitabine (n = 72). The addition of ibrutinib was well tolerated, and the number of adverse events was comparable for both arms. In the decitabine plus ibrutinib arm, 41% reached complete remission/complete remission with incomplete hematologic recovery (CR/CRi), the median overall survival (OS) was 11 months, and 2-year OS was 27%; these findings compared with 50% CR/CRi, median OS of 11.5 months, and 2-year OS of 21% for the decitabine group (not significant). Extensive molecular profiling at diagnosis revealed that patients with STAG2, IDH2, and ASXL1 mutations had significantly lower CR/CRi rates, whereas patients with mutations in TP53 had significantly higher CR/CRi rates. Furthermore, multicolor flow cytometry revealed that after 3 cycles of treatment, 28 (49%) of 57 patients with available bone marrow samples had no measurable residual disease. In this limited number of cases, measurable residual disease revealed no apparent impact on event-free survival and OS. In conclusion, the addition of ibrutinib does not improve the therapeutic efficacy of decitabine. This trial was registered at the Netherlands Trial Register (NL5751 [NTR6017]) and has EudraCT number 2015-002855-85.

Published
2020

50. Daratumumab in transfusion‐dependent patients with low or intermediate‐ 1 risk myelodysplastic syndromes

Author

Garcia‐Manero, Guillermo, primary, Diez‐Campelo, Maria, additional, Vellenga, Edo, additional, Jacoby, Meagan A., additional, Merchan, Brayan, additional, Breems, Dimitri, additional, Cortelezzi, Agostino, additional, Doronin, Vadim, additional, Gomez, Valle, additional, Beckers, Marielle, additional, Della Porta, Matteo Giovanni, additional, Varsos, Helen, additional, Xiu, Liang, additional, DeAngelis, Nikki, additional, Nnane, Ivo, additional, Rose, Esther, additional, and Eygen, Koen, additional

Published
2021
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