95 results on '"Mellqvist, U. H."'
Search Results
2. Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group
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Laubach, J, Garderet, L, Mahindra, A, Gahrton, G, Caers, J, Sezer, O, Voorhees, P, Leleu, X, Johnsen, H E, Streetly, M, Jurczyszyn, A, Ludwig, H, Mellqvist, U-H, Chng, W-J, Pilarski, L, Einsele, H, Hou, J, Turesson, I, Zamagni, E, Chim, C S, Mazumder, A, Westin, J, Lu, J, Reiman, T, Kristinsson, S, Joshua, D, Roussel, M, O'Gorman, P, Terpos, E, McCarthy, P, Dimopoulos, M, Moreau, P, Orlowski, R Z, Miguel, J S, Anderson, K C, Palumbo, A, Kumar, S, Rajkumar, V, Durie, B, and Richardson, P G
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- 2016
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3. P905: IXAZOMIB-THALIDOMIDE-DEXAMETHASONE INDUCTION FOLLOWED BY IXAZOMIB OR PLACEBO MAINTENANCE IN NON-TRANSPLANT ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS; LONG-TERM RESULTS OF HOVON-126/NMSG 21.13
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Groen, K., primary, Seefat, M. R., additional, van der Holt, B., additional, Schjesvold, F. H., additional, Stege, C. A., additional, Levin, M.-D., additional, Hansson, M., additional, Leys, R. B., additional, Regelink, J., additional, Waage, A., additional, Szatkowski, D., additional, Axelsson, P., additional, Do, T. H., additional, Svirskaite, A., additional, van der Spek, E., additional, Haukas, E., additional, Knut-Bojanowska, D., additional, Ypma, P. F., additional, Blimark, C., additional, Mellqvist, U.-H., additional, van de Donk, N. W., additional, Sonneveld, P., additional, Klostergaard, A., additional, Vangsted, A. J., additional, Abdilgaard, N., additional, and Zweegman, S., additional
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- 2022
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4. New drugs and novel mechanisms of action in multiple myeloma in 2013: a report from the International Myeloma Working Group (IMWG)
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Ocio, E M, Richardson, P G, Rajkumar, S V, Palumbo, A, Mateos, M V, Orlowski, R, Kumar, S, Usmani, S, Roodman, D, Niesvizky, R, Einsele, H, Anderson, K C, Dimopoulos, M A, Avet-Loiseau, H, Mellqvist, U-H, Turesson, I, Merlini, G, Schots, R, McCarthy, P, Bergsagel, L, Chim, C S, Lahuerta, J J, Shah, J, Reiman, A, Mikhael, J, Zweegman, S, Lonial, S, Comenzo, R, Chng, W J, Moreau, P, Sonneveld, P, Ludwig, H, Durie, B G M, and Miguel, J F S
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- 2014
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5. Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial
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Gimsing, P, Hjertner, Ø, Abildgaard, N, Andersen, N F, Dahl, T G, Gregersen, H, Klausen, T W, Mellqvist, U-H, Linder, O, Lindås, R, Clausen, Tøffner N, and Lenhoff, S
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- 2015
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6. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group
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Fernández de Larrea, C, Kyle, R A, Durie, B G M, Ludwig, H, Usmani, S, Vesole, D H, Hajek, R, San Miguel, J F, Sezer, O, Sonneveld, P, Kumar, S K, Mahindra, A, Comenzo, R, Palumbo, A, Mazumber, A, Anderson, K C, Richardson, P G, Badros, A Z, Caers, J, Cavo, M, LeLeu, X, Dimopoulos, M A, Chim, C S, Schots, R, Noeul, A, Fantl, D, Mellqvist, U-H, Landgren, O, Chanan-Khan, A, Moreau, P, Fonseca, R, Merlini, G, Lahuerta, J J, Bladé, J, Orlowski, R Z, and Shah, J J
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- 2013
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7. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group
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Moreau, P. Kumar, S.K. San Miguel, J. Davies, F. Zamagni, E. Bahlis, N. Ludwig, H. Mikhael, J. Terpos, E. Schjesvold, F. Martin, T. Yong, K. Durie, B.G.M. Facon, T. Jurczyszyn, A. Sidana, S. Raje, N. van de Donk, N. Lonial, S. Cavo, M. Kristinsson, S.Y. Lentzsch, S. Hajek, R. Anderson, K.C. João, C. Einsele, H. Sonneveld, P. Engelhardt, M. Fonseca, R. Vangsted, A. Weisel, K. Baz, R. Hungria, V. Berdeja, J.G. Leal da Costa, F. Maiolino, A. Waage, A. Vesole, D.H. Ocio, E.M. Quach, H. Driessen, C. Bladé, J. Leleu, X. Riva, E. Bergsagel, P.L. Hou, J. Chng, W.J. Mellqvist, U.-H. Dytfeld, D. Harousseau, J.-L. Goldschmidt, H. Laubach, J. Munshi, N.C. Gay, F. Beksac, M. Costa, L.J. Kaiser, M. Hari, P. Boccadoro, M. Usmani, S.Z. Zweegman, S. Holstein, S. Sezer, O. Harrison, S. Nahi, H. Cook, G. Mateos, M.-V. Rajkumar, S.V. Dimopoulos, M.A. Richardson, P.G.
- Abstract
This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes. © 2021 Elsevier Ltd
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- 2021
8. Optimizing the use of lenalidomide in relapsed or refractory multiple myeloma: consensus statement
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Dimopoulos, M A, Palumbo, A, Attal, M, Beksaç, M, Davies, F E, Delforge, M, Einsele, H, Hajek, R, Harousseau, J-L, da Costa, F Leal, Ludwig, H, Mellqvist, U-H, Morgan, G J, San-Miguel, J F, Zweegman, S, and Sonneveld, P
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- 2011
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9. Autologous haematopoietic stem-cell transplantation versus bortezomib–melphalan–prednisone, with or without bortezomib–lenalidomide–dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study
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Cavo, M. Gay, F. Beksac, M. Pantani, L. Petrucci, M.T. Dimopoulos, M.A. Dozza, L. van der Holt, B. Zweegman, S. Oliva, S. van der Velden, V.H.J. Zamagni, E. Palumbo, G.A. Patriarca, F. Montefusco, V. Galli, M. Maisnar, V. Gamberi, B. Hansson, M. Belotti, A. Pour, L. Ypma, P. Grasso, M. Croockewit, A. Ballanti, S. Offidani, M. Vincelli, I.D. Zambello, R. Liberati, A.M. Andersen, N.F. Broijl, A. Troia, R. Pascarella, A. Benevolo, G. Levin, M.-D. Bos, G. Ludwig, H. Aquino, S. Morelli, A.M. Wu, K.L. Boersma, R. Hajek, R. Durian, M. von dem Borne, P.A. Caravita di Toritto, T. Zander, T. Specchia, G. Waage, A. Gimsing, P. Mellqvist, U.-H. van Marwijk Kooy, M. Minnema, M. Mandigers, C. Cafro, A.M. Palmas, A. Carvalho, S. Spencer, A. Boccadoro, M. Sonneveld, P.
- Abstract
Background: The emergence of highly active novel agents has led some to question the role of autologous haematopoietic stem-cell transplantation (HSCT) and subsequent consolidation therapy in newly diagnosed multiple myeloma. We therefore compared autologous HSCT with bortezomib–melphalan–prednisone (VMP) as intensification therapy, and bortezomib–lenalidomide–dexamethasone (VRD) consolidation therapy with no consolidation. Methods: In this randomised, open-label, phase 3 study we recruited previously untreated patients with multiple myeloma at 172 academic and community practice centres of the European Myeloma Network. Eligible patients were aged 18–65 years, had symptomatic multiple myeloma stage 1–3 according to the International Staging System (ISS), measurable disease (serum M protein >10 g/L or urine M protein >200 mg in 24 h or abnormal free light chain [FLC] ratio with involved FLC >100 mg/L, or proven plasmacytoma by biopsy), and WHO performance status grade 0–2 (grade 3 was allowed if secondary to myeloma). Patients were first randomly assigned (1:1) to receive either four 42-day cycles of bortezomib (1·3 mg/m2 administered intravenously or subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32) combined with melphalan (9 mg/m2 administered orally on days 1–4) and prednisone (60 mg/m2 administered orally on days 1–4) or autologous HSCT after high-dose melphalan (200 mg/m2), stratified by site and ISS disease stage. In centres with a double HSCT policy, the first randomisation (1:1:1) was to VMP or single or double HSCT. Afterwards, a second randomisation assigned patients to receive two 28-day cycles of consolidation therapy with bortezomib (1·3 mg/m2 either intravenously or subcutaneously on days 1, 4, 8, and 11), lenalidomide (25 mg orally on days 1–21), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12) or no consolidation; both groups received lenalidomide maintenance therapy (10 mg orally on days 1–21 of a 28-day cycle). The primary outcomes were progression-free survival from the first and second randomisations, analysed in the intention-to-treat population, which included all patients who underwent each randomisation. All patients who received at least one dose of study drugs were included in the safety analyses. This study is registered with the EU Clinical Trials Register (EudraCT 2009-017903-28) and ClinicalTrials.gov (NCT01208766), and has completed recruitment. Findings: Between Feb 25, 2011, and April 3, 2014, 1503 patients were enrolled. 1197 patients were eligible for the first randomisation, of whom 702 were assigned to autologous HSCT and 495 to VMP; 877 patients who were eligible for the first randomisation underwent the second randomisation to VRD consolidation (n=449) or no consolidation (n=428). The data cutoff date for the current analysis was Nov 26, 2018. At a median follow-up of 60·3 months (IQR 52·2–67·6), median progression-free survival was significantly improved with autologous HSCT compared with VMP (56·7 months [95% CI 49·3–64·5] vs 41·9 months [37·5–46·9]; hazard ratio [HR] 0·73, 0·62–0·85; p=0·0001). For the second randomisation, the number of events of progression or death at data cutoff was lower than that preplanned for the final analysis; therefore, the results from the second protocol-specified interim analysis, when 66% of events were reached, are reported (data cutoff Jan 18, 2018). At a median follow-up of 42·1 months (IQR 32·3–49·2), consolidation therapy with VRD significantly improved median progression-free survival compared with no consolidation (58·9 months [54·0–not estimable] vs 45·5 months [39·5–58·4]; HR 0·77, 0·63–0·95; p=0·014). The most common grade ≥3 adverse events in the autologous HSCT group compared to the VMP group included neutropenia (513 [79%] of 652 patients vs 137 [29%] of 472 patients), thrombocytopenia (541 [83%] vs 74 [16%]), gastrointestinal disorders (80 [12%] vs 25 [5%]), and infections (192 [30%] vs 18 [4%]). 239 (34%) of 702 patients in the autologous HSCT group and 135 (27%) of 495 in the VMP group had at least one serious adverse event. Infection was the most common serious adverse event in each of the treatment groups (206 [56%] of 368 and 70 [37%] of 189). 38 (12%) of 311 deaths from first randomisation were likely to be treatment related: 26 (68%) in the autologous HSCT group and 12 (32%) in the VMP group, most frequently due to infections (eight [21%]), cardiac events (six [16%]), and second primary malignancies (20 [53%]). Interpretation: This study supports the use of autologous HSCT as intensification therapy and the use of consolidation therapy in patients with newly diagnosed multiple myeloma, even in the era of novel agents. The role of high-dose chemotherapy needs to be reassessed in future studies, in particular in patients with undetectable minimal residual disease after four-drug induction regimens including a monoclonal antiboby combined with an immunomodulatory agent and a proteasome inhibitor plus dexamethasone. Funding: Janssen and Celgene. © 2020 Elsevier Ltd
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- 2020
10. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group
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de Larrea, Fernandez C, Kyle, R A, Durie, B GM, Ludwig, H, Usmani, S, Vesole, D H, Hajek, R, San Miguel, J F, Sezer, O, Sonneveld, P, Kumar, S K, Mahindra, A, Comenzo, R, Palumbo, A, Mazumber, A, Anderson, K C, Richardson, P G, Badros, A Z, Caers, J, Cavo, M, LeLeu, X, Dimopoulos, M A, Chim, C S, Schots, R, Noeul, A, Fantl, D, Mellqvist, U-H, Landgren, O, Chanan-Khan, A, Moreau, P, Fonseca, R, Merlini, G, Lahuerta, J J, Blade, J, Orlowski, R Z, and Shah, J J
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- 2013
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11. Alleviating oxidative stress in cancer immunotherapy: a role for histamine?
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Hellstrand, K, Brune, M, Dahlgren, C, Hansson, M, Hermodsson, S, Lindnér, P, Mellqvist, U-H, and Naredi, P
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- 2000
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12. Melphalan 100 mg/m2 with stem cell support as first-relapse treatment is safe and effective for myeloma patients with long remission after autologous stem cell transplantation: P893
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Blimark, C., Veskovski, L., Brune, M., Westin, J., Holmberg, E., Hjorth, M., Rodjer, S., Andersson, P. O., and Mellqvist, U. H.
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- 2011
13. Impaired Stem Cell Mobilization by Fludarabine in MM: Results from a Randomized Phase II Trial: A554
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Johnsen, H E, Lennhoff, S, Tangen, Gluud, C, Knudsen, L M, Mylin, A K, Gimsing, P, Gregersen, H, Abildgaard, N, Nielsen, J L, Andersen, N F, Plesner, T, Vangsted, A J, Mourits-Andersen, T, and Mellqvist, U H
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- 2009
14. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial
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Richardson, P.G. Oriol, A. Beksac, M. Liberati, A.M. Galli, M. Schjesvold, F. Lindsay, J. Weisel, K. White, D. Facon, T. San Miguel, J. Sunami, K. O'Gorman, P. Sonneveld, P. Robak, P. Semochkin, S. Schey, S. Yu, X. Doerr, T. Bensmaine, A. Biyukov, T. Peluso, T. Zaki, M. Anderson, K. Dimopoulos, M. Abildgaard, N. Adler, H. Altuntas, F. Akay, O.M. Amin, B. Anagnostopoulos, A. Anderson, L. Anttila, P. Araujo, C. Arce-Lara, C. Aydin, Y. Basu, S. Battini, R. Beeker, T. Benboubker, L. Ben-Yehuda, D. Bladé, J. Blau, I.W. Boccia, R. Burke, L. Byeff, P. Cascavilla, N. Cavo, M. Chantry, A. Charles, Y. Chaudhry, A. Corso, A. Coyne, M. De Arriba, F. Delimpasi, S. Desjardins, P. Dhakal, B. Di Bartolomeo, P. Di Raimondo, F. Dürig, J. Engelhardt, M. Escoffre-Barbe, M. Esteves, G. Flogegard, M. Gabrail, N. Gamberi, B. Garrison, M. Gay, J. Gisslinger, H. Goldschmidt, H. Goncalves, C. Gressot, L. Grosicki, S. Hanna, W. Hayden, P. Henriques Bernardo, M.M. Hermann, R. Holden, V. Honkalehto, K. Huben, M. Huffman, J. Hunter, H. Hus, M. Jagasia, M. Jagganath, S. Janakiram, M. Jaiyesimi, I. Jenner, M. João, C. Johnson, P. Jurcyszyn, A. Kalayoğlu Beşişik, S. Kambhampati, S. Kanate, A. Karadoğan, I. Khojasteh, A. Kirkel, D. Komarnicki, M. Krauth, M.-T. Kuriakose, P. Larocca, A. Lauri, B. Leleu, X. Lucio, P. Luppi, M. Mangiacavalli, S. Mariette, C. Matsue, K. Mellqvist, U.-H. Mendeleeva, L. Meshad, M. Miller, C. Mohrbacher, A. Moreau, P. Morelli, A.M. Müldür, E. Naassan, A. Nahi, H. Nair, R. O'Dwyer, M. Öngören Aydin, S. Openshaw, T. O'Rourke, T. Osswald, M. Overton, L. Pati, A. Pavic, M. Pegourie, B. Pehlivan, M. Pierola, A.A. Plesner, T. Pluta, A. Rabin, N. Ramasamy, K. Rambaldi, A. Rodriguez, P. Röllig, C. Rosenblatt, J. Rosenbluth, J. Salomo, M. Samoylova, O. Sastre Moral, J. Sati, H. Selleri, C. Shafeek, S. Shinagawa, A. Sleckman, B. Smith, C. Sonmez, M. Stone, C. Streetly, M. Suzuki, K. Taetle, R. Tafuri, A. Takezako, N. Teke, H.Ü. Vapaatalo, M. Vassilopoulos, G. Verma, A. Vidito, S. Viterbo, L. Vural, F. Wang, X.S. Yağci, M. Yee, A. OPTIMISMM trial investigators
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hemic and lymphatic diseases - Abstract
Background: As lenalidomide becomes increasingly established for upfront treatment of multiple myeloma, patients refractory to this drug represent a population with an unmet need. The combination of pomalidomide, bortezomib, and dexamethasone has shown promising results in phase 1/2 trials of patients with relapsed or refractory multiple myeloma. We aimed to assess the efficacy and safety of this triplet regimen in patients with relapsed or refractory multiple myeloma who previously received lenalidomide. Methods: We did a randomised, open-label, phase 3 trial at 133 hospitals and research centres in 21 countries. We enrolled patients (aged ≥18 years)with a diagnosis of multiple myeloma and measurable disease, an Eastern Cooperative Oncology Group performance status of 0–2, who received one to three previous regimens, including a lenalidomide-containing regimen for at least two consecutive cycles. We randomly assigned patients (1:1)to bortezomib and dexamethasone with or without pomalidomide using a permutated blocked design in blocks of four, stratified according to age, number of previous regimens, and concentration of β2 microglobulin at screening. Bortezomib (1·3 mg/m2)was administered intravenously until protocol amendment 1 then either intravenously or subcutaneously on days 1, 4, 8, and 11 for the first eight cycles and subsequently on days 1 and 8. Dexamethasone (20 mg [10 mg if age >75 years])was administered orally on the same days as bortezomib and the day after. Patients allocated pomalidomide received 4 mg orally on days 1–14. Treatment cycles were every 21 days. The primary endpoint was progression-free survival in the intention-to-treat population, as assessed by an independent review committee. Safety was assessed in all patients who received at least one dose of study medication. This trial is registered at ClinicalTrials.gov, number NCT01734928; patients are no longer being enrolled. Findings: Between Jan 7, 2013, and May 15, 2017, 559 patients were enrolled. 281 patients were assigned pomalidomide, bortezomib, and dexamethasone and 278 were allocated bortezomib and dexamethasone. Median follow-up was 15·9 months (IQR 9·9–21·7). Pomalidomide, bortezomib, and dexamethasone significantly improved progression-free survival compared with bortezomib and dexamethasone (median 11·20 months [95% CI 9·66–13·73]vs 7·10 months [5·88–8·48]; hazard ratio 0·61, 95% CI 0·49–0·77; p
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- 2019
15. Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma (vol 9, 3707, 2018)
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Went, M, Sud, A, Foersti, A, Halvarsson, B-M, Weinhold, N, Kimber, S, van Duin, M, Thorleifsson, G, Holroyd, A, Johnson, DC, Li, N, Orlando, G, Law, PJ, Ali, M, Chen, B, Mitchell, JS, Gudbjartsson, DF, Kuiper, R, Stephens, OW, Bertsch, U, Broderick, P, Campo, C, Bandapalli, OR, Einsele, H, Gregory, WA, Gullberg, U, Hillengass, J, Hoffmann, P, Jackson, GH, Joeckel, K-H, Johnsson, E, Kristinsson, SY, Mellqvist, U-H, Nahi, H, Easton, D, Pharoah, P, Dunning, A, Peto, J, Canzian, F, Swerdlow, A, Eeles, RA, Kote-Jarai, Z, Muir, K, Pashayan, N, Henderson, BE, Haiman, CA, Benlloch, S, Schumacher, FR, Al Olama, AA, Berndt, SI, Conti, DV, Wiklund, F, Chanock, S, Stevens, VL, Tangen, CM, Batra, J, Clements, J, Gronberg, H, Schleutker, J, Albanes, D, Weinstein, S, Wolk, A, West, C, Mucci, L, Cancel-Tassin, G, Koutros, S, Sorensen, KD, Grindedal, EM, Neal, DE, Hamdy, FC, Donovan, JL, Travis, RC, Hamilton, RJ, Ingles, SA, Rosenstein, B, Lu, Y-J, Giles, GG, Kibel, AS, Vega, A, Kogevinas, M, Penney, KL, Park, JY, Stanford, JL, Cybulski, C, Nordestgaard, BG, Brenner, H, Maier, C, Kim, J, John, EM, Teixeira, MR, Neuhausen, SL, De Ruyck, K, Razack, A, Newcomb, LF, Lessel, D, Kaneva, R, Usmani, N, Claessens, F, Townsend, PA, Gago-Dominguez, M, Roobol, MJ, Menegaux, F, Khaw, K-T, Cannon-Albright, L, Pandha, H, Thibodeau, SN, Nickel, J, Noethen, MM, Rafnar, T, Ross, FM, Filho, MIDS, Thomsen, H, Turesson, I, Vangsted, A, Andersen, NF, Waage, A, Walker, BA, Wihlborg, A-K, Broyl, A, Davies, FE, Thorsteinsdottir, U, Langer, C, Hansson, M, Goldschmidt, H, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, GJ, Hemminki, K, Nilsson, B, Houlston, RS, Went, M, Sud, A, Foersti, A, Halvarsson, B-M, Weinhold, N, Kimber, S, van Duin, M, Thorleifsson, G, Holroyd, A, Johnson, DC, Li, N, Orlando, G, Law, PJ, Ali, M, Chen, B, Mitchell, JS, Gudbjartsson, DF, Kuiper, R, Stephens, OW, Bertsch, U, Broderick, P, Campo, C, Bandapalli, OR, Einsele, H, Gregory, WA, Gullberg, U, Hillengass, J, Hoffmann, P, Jackson, GH, Joeckel, K-H, Johnsson, E, Kristinsson, SY, Mellqvist, U-H, Nahi, H, Easton, D, Pharoah, P, Dunning, A, Peto, J, Canzian, F, Swerdlow, A, Eeles, RA, Kote-Jarai, Z, Muir, K, Pashayan, N, Henderson, BE, Haiman, CA, Benlloch, S, Schumacher, FR, Al Olama, AA, Berndt, SI, Conti, DV, Wiklund, F, Chanock, S, Stevens, VL, Tangen, CM, Batra, J, Clements, J, Gronberg, H, Schleutker, J, Albanes, D, Weinstein, S, Wolk, A, West, C, Mucci, L, Cancel-Tassin, G, Koutros, S, Sorensen, KD, Grindedal, EM, Neal, DE, Hamdy, FC, Donovan, JL, Travis, RC, Hamilton, RJ, Ingles, SA, Rosenstein, B, Lu, Y-J, Giles, GG, Kibel, AS, Vega, A, Kogevinas, M, Penney, KL, Park, JY, Stanford, JL, Cybulski, C, Nordestgaard, BG, Brenner, H, Maier, C, Kim, J, John, EM, Teixeira, MR, Neuhausen, SL, De Ruyck, K, Razack, A, Newcomb, LF, Lessel, D, Kaneva, R, Usmani, N, Claessens, F, Townsend, PA, Gago-Dominguez, M, Roobol, MJ, Menegaux, F, Khaw, K-T, Cannon-Albright, L, Pandha, H, Thibodeau, SN, Nickel, J, Noethen, MM, Rafnar, T, Ross, FM, Filho, MIDS, Thomsen, H, Turesson, I, Vangsted, A, Andersen, NF, Waage, A, Walker, BA, Wihlborg, A-K, Broyl, A, Davies, FE, Thorsteinsdottir, U, Langer, C, Hansson, M, Goldschmidt, H, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, GJ, Hemminki, K, Nilsson, B, and Houlston, RS
- Abstract
The original version of this Article contained an error in the spelling of a member of the PRACTICAL Consortium, Manuela Gago-Dominguez, which was incorrectly given as Manuela Gago Dominguez. This has now been corrected in both the PDF and HTML versions of the Article. Furthermore, in the original HTML version of this Article, the order of authors within the author list was incorrect. The PRACTICAL consortium was incorrectly listed after Richard S. Houlston and should have been listed after Nora Pashayan. This error has been corrected in the HTML version of the Article; the PDF version was correct at the time of publication.
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- 2019
16. First Report on OS and Improved PFS In a Completed Phase 2 Study (O-12-M1) of Melflufen in Advanced RRMM
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Bringhen, S., Paba-Prada, C., Voorhees, P., Plesner, T., Sonneveld, P., Mellqvist, U. H., Zonder, J., Reeves, B., Palumbo, A., Byrne, C., Harmenberg, J., Nordstrom, E., Zubair, H., Lindberg, J., and Richardson, P. G.
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- 2018
17. Prevention and management of adverse events of novel agents in multiple myeloma: A consensus of the European Myeloma Network
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Ludwig, H. Delforge, M. Facon, T. Einsele, H. Gay, F. Moreau, P. Avet-Loiseau, H. Boccadoro, M. Hajek, R. Mohty, M. Cavo, M. Dimopoulos, M. A. San-Miguel, J. F. Terpos, E. Zweegman, S. Garderet, L. Mateos, M.-V. Cook, G. Leleu, X. Goldschmidt, H. Jackson, G. Kaiser, M. Weisel, K. van de Donk, N. W. C. J. Waage, A. Beksac, M. Mellqvist, U. H. Engelhardt, M. Caers, J. Driessen, C. Sonneveld, P.
- Abstract
During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drugs classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events.Leukemia accepted article preview online, 18 December 2017. doi:10.1038/leu.2017.353.
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- 2018
18. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study
- Author
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Mohty, M. Terpos, E. Mateos, M.-V. Cavo, M. Lejniece, S. Beksac, M. Bekadja, M.A. Legiec, W. Dimopoulos, M. Stankovic, S. Durán, M.S. De Stefano, V. Corso, A. Kochkareva, Y. Laane, E. Berthou, C. Salwender, H. Masliak, Z. Pečeliūnas, V. Willenbacher, W. Silva, J. Louw, V. Nemet, D. Borbényi, Z. Abadi, U. Pedersen, R.S. Černelč, P. Potamianou, A. Couturier, C. Feys, C. Thoret-Bauchet, F. Boccadoro, M. Bekadja, M. Hamladji, R.-M. Ali, H.A. Hamdi, S. Touhami, H. Mansour, N.S. Linkesch, W. Abildgaard, N. Hein, M. Eveillard, J.R. Yamani, A.E. Moreau, P. Sanhes, L. Lepeu, G. Laribi, K. Jourdan, E. Fitoussi, O. Allangba, O. Fleury, J. Escoffre, M. Benramdane, R. Cartron, G. Dine, G. Legouffe, E. Harich, H.-D. Illmer, T. Dörfel, S. Hannig, C.V. Koenigsmann, M. Prange-Krex, G. Tamm, I. Zeller, W. Maasberg, M. Schlag, R. Klausmann, M. Uhlig, J. Alkemper, B. Schütz, S. Tessen, H.-W. Mohr, B. Schmidt, P. Heinrich, B. Hebart, H. Seipelt, G. Zoeller, T. Heits, F. Müller-Naendrup, C. Hansen, R. Repp, R. Von Weikersthal, L.F. Schmits, R. Heßling, J. Krammer-Steiner, B. Janzen, V. Schauer, M. Grüner, M.W. Kisro, J. Denzlinger, C. Freier, W. Junghanss, C. Görner, M. Laichinger, K. Ostermann, H. Dürk, H. Hess, G. Reich, G. Matsouka, P. Pouli, A. Anagnostopoulos, A. Masszi, T. Ivanyi, J. Szomor, A. Nagler, A. Magen, H. Avivi, I. Quitt, M. Palumbo, A. Za, T. Vallisa, D. Foa, R. Bosi, A. Vacca, A. Lanza, F. Palazzo, G. Avvisati, G. Ferrara, F. Consoli, U. Cantonetti, M. Angelucci, E. Califano, C. Di Raimondo, F. Guarini, A. Musso, M. Pizzuti, M. Giuliani, N. Ardizzoia, A. Di Renzo, N. Gaidano, G. Gozzetti, A. Pitini, V. Farina, G. Centurioni, R. De Fabritiis, P. Iuliano, F. La Nasa, G. La Verde, G. Pane, F. Recine, U. La Targia, M. Mineo, G. Cangialosi, C. Fagnani, D. Federici, A. Romano, A. Specchia, G. Storti, S. Bongarzoni, V. Bacigalupo, A. Gobbi, M. Latte, G. Mannina, D. Capalbo, S. Jurgutis, M. Woszczyk, D. Hołojda, J. Gornik, S. Pluta, A. Morawiec-Szymonik, E. Kyrcz-Krzemien, S. Homenda, W. Grosicki, S. Sulek, K. Lange, A. Kloczko, J. Starzak-Gwozdz, J. Hellmann, A. Komarnicki, M. Kuliczkowski, K. Viveiros, C. Gonçalves, C. Esefyeva, N. Kaplanov, K. Volodicheva, E. Laricheva, E. Dergacheva, V. Chukavina, M. Volchenko, N. Nazarova, I. Anchukova, L. Ovanesova, E. Salogub, G. Magomedova, L. Kuznetsova, I. Osyunikhina, S. Serdyuk, O. Karyagina, E. Ivanova, V. Černelč, S.P. Coetzee, C. Gunther, K. Moodley, D. Duran, S. Gutiérrez, A.E. De Oteyza, J.P. Capote, F.J. Casanova, M. Sanchez, J.M. Rios-Herranz, E. Ibañez-Garcia, J. Herranz, M.J. Hernandez, B. Sanchez, S.S. Escalante, F. Carnicero, F. Lleonart, J.B. Gironella, M. Martínez, R. De La Guia, A.L. Palomera, L. Iglesias, R. Ramos, F.S. De La Serna, J. Sanchez, P.G. Vidal, J.B. Morfa, M.D. Beksac, T.-M. Vural, F. Aydin, Y. Unal, A. Goker, H. Bilgir, O. Guvenc, B. Turgut, M. Ozet, G.G. Ali, R. Kyselyova, M. Glushko, N. Vybyrana, R. Skrypnyk, I. Tretyak, N. Kharchevska, T. Dyagil, I. Popovs'ka, T. Shimanskiy, V. Lysa, T. Oliynyk, H. Vilchevskaya, K. Kryachok, I. Popovych, Y. Romanyuk, N. Yushchenko, N. Kaplan, P. Rekhtman, G. Pylypenko, H. Kozlov, V. Drach, J. Harousseau, J.-L. Einsele, H. Goldschmidt, H. Facon, T. Michalet, M. Savchenko, V.G. De la Rubia, J. Cook, G. Mellqvist, U.-H. Ludwig, H. EMMOS Investigators
- Abstract
Multiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits. © 2018 The Authors
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- 2018
19. PF628 O-12-M1: AN EVALUATION OF TIME TO NEXT TREATMENT IN MELFLUFEN AND DEXAMETHASONE-TREATED PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA
- Author
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Bringhen, S., primary, Richardson, P.G., additional, Voorhees, P., additional, Plesner, T., additional, Mellqvist, U.-H., additional, Zonder, J.A., additional, Reeves, B., additional, Zavisic, S., additional, Harmenberg, J., additional, Obermüller, J., additional, and Sonneveld, P., additional
- Published
- 2019
- Full Text
- View/download PDF
20. Plasma thrombopoietin levels in thrombocytopenic states: implication for a regulatory role of bone marrow megakaryocytes
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Hou, M., Andersson, P. O., Stockelberg, D., Mellqvist, U. H., Ridell, B., and Wadenvik, H.
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- 1998
21. Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.
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Went, M, Sud, A, Försti, A, Halvarsson, B-M, Weinhold, N, Kimber, S, van Duin, M, Thorleifsson, G, Holroyd, A, Johnson, DC, Li, N, Orlando, G, Law, PJ, Ali, M, Chen, B, Mitchell, JS, Gudbjartsson, DF, Kuiper, R, Stephens, OW, Bertsch, U, Broderick, P, Campo, C, Bandapalli, OR, Einsele, H, Gregory, WA, Gullberg, U, Hillengass, J, Hoffmann, P, Jackson, GH, Jöckel, K-H, Johnsson, E, Kristinsson, SY, Mellqvist, U-H, Nahi, H, Easton, D, Pharoah, P, Dunning, A, Peto, J, Canzian, F, Swerdlow, A, Eeles, RA, Kote-Jarai, Z, Muir, K, Pashayan, N, Nickel, J, Nöthen, MM, Rafnar, T, Ross, FM, da Silva Filho, MI, Thomsen, H, Turesson, I, Vangsted, A, Andersen, NF, Waage, A, Walker, BA, Wihlborg, A-K, Broyl, A, Davies, FE, Thorsteinsdottir, U, Langer, C, Hansson, M, Goldschmidt, H, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, GJ, Hemminki, K, Nilsson, B, Houlston, RS, PRACTICAL consortium, Went, M, Sud, A, Försti, A, Halvarsson, B-M, Weinhold, N, Kimber, S, van Duin, M, Thorleifsson, G, Holroyd, A, Johnson, DC, Li, N, Orlando, G, Law, PJ, Ali, M, Chen, B, Mitchell, JS, Gudbjartsson, DF, Kuiper, R, Stephens, OW, Bertsch, U, Broderick, P, Campo, C, Bandapalli, OR, Einsele, H, Gregory, WA, Gullberg, U, Hillengass, J, Hoffmann, P, Jackson, GH, Jöckel, K-H, Johnsson, E, Kristinsson, SY, Mellqvist, U-H, Nahi, H, Easton, D, Pharoah, P, Dunning, A, Peto, J, Canzian, F, Swerdlow, A, Eeles, RA, Kote-Jarai, Z, Muir, K, Pashayan, N, Nickel, J, Nöthen, MM, Rafnar, T, Ross, FM, da Silva Filho, MI, Thomsen, H, Turesson, I, Vangsted, A, Andersen, NF, Waage, A, Walker, BA, Wihlborg, A-K, Broyl, A, Davies, FE, Thorsteinsdottir, U, Langer, C, Hansson, M, Goldschmidt, H, Kaiser, M, Sonneveld, P, Stefansson, K, Morgan, GJ, Hemminki, K, Nilsson, B, Houlston, RS, and PRACTICAL consortium
- Abstract
Genome-wide association studies (GWAS) have transformed our understanding of susceptibility to multiple myeloma (MM), but much of the heritability remains unexplained. We report a new GWAS, a meta-analysis with previous GWAS and a replication series, totalling 9974 MM cases and 247,556 controls of European ancestry. Collectively, these data provide evidence for six new MM risk loci, bringing the total number to 23. Integration of information from gene expression, epigenetic profiling and in situ Hi-C data for the 23 risk loci implicate disruption of developmental transcriptional regulators as a basis of MM susceptibility, compatible with altered B-cell differentiation as a key mechanism. Dysregulation of autophagy/apoptosis and cell cycle signalling feature as recurrently perturbed pathways. Our findings provide further insight into the biological basis of MM.
- Published
- 2018
22. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study
- Author
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Mohty, M., Terpos, E., Mateos, M. -V., Cavo, M., Lejniece, S., Beksac, M., Bekadja, M. A., Legiec, W., Dimopoulos, M., Stankovic, S., Duran, M. S., De Stefano, Valerio, Corso, A., Kochkareva, Y., Laane, E., Berthou, C., Salwender, H., Masliak, Z., Peceliunas, V., Willenbacher, W., Silva, J., Louw, V., Nemet, D., Borbenyi, Z., Abadi, U., Pedersen, R. S., Cernelc, P., Potamianou, A., Couturier, C., Feys, C., Thoret-Bauchet, F., Boccadoro, M., Bekadja, M., Hamladji, R. -M., Ali, H. A., Hamdi, S., Touhami, H., Mansour, N. S., Linkesch, W., Abildgaard, N., Hein, M., Eveillard, J. R., Yamani, A. E., Moreau, P., Sanhes, L., Lepeu, G., Laribi, K., Jourdan, E., Fitoussi, O., Allangba, O., Fleury, J., Escoffre, M., Benramdane, R., Cartron, G., Dine, G., Legouffe, E., Harich, H. -D., Illmer, T., Dorfel, S., Hannig, C. V., Koenigsmann, M., Prange-Krex, G., Tamm, I., Zeller, W., Maasberg, M., Schlag, R., Klausmann, M., Uhlig, J., Alkemper, B., Schutz, S., Tessen, H. -W., Mohr, B., Schmidt, P., Heinrich, B., Hebart, H., Seipelt, G., Zoeller, T., Heits, F., Muller-Naendrup, C., Hansen, R., Repp, R., Von Weikersthal, L. F., Schmits, R., Hessling, J., Krammer-Steiner, B., Janzen, V., Schauer, M., Gruner, M. W., Kisro, J., Denzlinger, C., Freier, W., Junghanss, C., Gorner, M., Laichinger, K., Ostermann, H., Durk, H., Hess, G., Reich, G., Matsouka, P., Pouli, A., Anagnostopoulos, A., Masszi, T., Ivanyi, J., Szomor, A., Nagler, A., Magen, H., Avivi, I., Quitt, M., Palumbo, A., Za, Tommaso, Vallisa, D., Foa, R., Bosi, A., Vacca, A., Lanza, F., Palazzo, G., Avvisati, G., Ferrara, F., Consoli, U., Cantonetti, M., Angelucci, E., Califano, C., Di Raimondo, F., Guarini, A., Musso, M., Pizzuti, M., Giuliani, N., Ardizzoia, A., Di Renzo, N., Gaidano, G., Gozzetti, A., Pitini, V., Farina, G., Centurioni, R., De Fabritiis, P., Iuliano, F., La Nasa, G., La Verde, G., Pane, F., Recine, U., La Targia, M., Mineo, G., Cangialosi, C., Fagnani, D., Federici, A., Romano, A., Specchia, G., Storti, Sergio, Bongarzoni, V., Bacigalupo, Andrea, Gobbi, M., Latte, G., Mannina, D., Capalbo, S., Jurgutis, M., Woszczyk, D., Holojda, J., Gornik, S., Pluta, A., Morawiec-Szymonik, E., Kyrcz-Krzemien, S., Homenda, W., Grosicki, S., Sulek, K., Lange, A., Kloczko, J., Starzak-Gwozdz, J., Hellmann, A., Komarnicki, M., Kuliczkowski, K., Viveiros, C., Goncalves, C., Esefyeva, N., Kaplanov, K., Volodicheva, E., Laricheva, E., Dergacheva, V., Chukavina, M., Volchenko, N., Nazarova, I., Anchukova, L., Ovanesova, E., Salogub, G., Magomedova, L., Kuznetsova, I., Osyunikhina, S., Serdyuk, O., Karyagina, E., Ivanova, V., Cernelc, S. P., Coetzee, C., Gunther, K., Moodley, D., Duran, S., Gutierrez, A. E., De Oteyza, J. P., Capote, F. J., Casanova, M., Sanchez, J. M., Rios-Herranz, E., Ibanez-Garcia, J., Herranz, M. J., Hernandez, B., Sanchez, S. S., Escalante, F., Carnicero, F., Lleonart, J. B., Gironella, M., Martinez, R., De La Guia, A. L., Palomera, L., Iglesias, R., Ramos, F. S., De La Serna, J., Sanchez, P. G., Vidal, J. B., Morfa, M. D., Beksac, T. -M., Vural, F., Aydin, Y., Unal, A., Goker, H., Bilgir, O., Guvenc, B., Turgut, M., Ozet, G. G., Ali, R., Kyselyova, M., Glushko, N., Vybyrana, R., Skrypnyk, I., Tretyak, N., Kharchevska, T., Dyagil, I., Popovs'Ka, T., Shimanskiy, V., Lysa, T., Oliynyk, H., Vilchevskaya, K., Kryachok, I., Popovych, Y., Romanyuk, N., Yushchenko, N., Kaplan, P., Rekhtman, G., Pylypenko, H., Kozlov, V., Drach, J., Harousseau, J. -L., Einsele, H., Goldschmidt, H., Facon, T., Michalet, M., Savchenko, V. G., De la Rubia, J., Cook, G., Mellqvist, U. -H., Ludwig, H., De Stefano V. (ORCID:0000-0002-5178-5827), Za T., Storti S. (ORCID:0000-0002-4374-3985), Bacigalupo A. (ORCID:0000-0002-9119-567X), Mohty, M., Terpos, E., Mateos, M. -V., Cavo, M., Lejniece, S., Beksac, M., Bekadja, M. A., Legiec, W., Dimopoulos, M., Stankovic, S., Duran, M. S., De Stefano, Valerio, Corso, A., Kochkareva, Y., Laane, E., Berthou, C., Salwender, H., Masliak, Z., Peceliunas, V., Willenbacher, W., Silva, J., Louw, V., Nemet, D., Borbenyi, Z., Abadi, U., Pedersen, R. S., Cernelc, P., Potamianou, A., Couturier, C., Feys, C., Thoret-Bauchet, F., Boccadoro, M., Bekadja, M., Hamladji, R. -M., Ali, H. A., Hamdi, S., Touhami, H., Mansour, N. S., Linkesch, W., Abildgaard, N., Hein, M., Eveillard, J. R., Yamani, A. E., Moreau, P., Sanhes, L., Lepeu, G., Laribi, K., Jourdan, E., Fitoussi, O., Allangba, O., Fleury, J., Escoffre, M., Benramdane, R., Cartron, G., Dine, G., Legouffe, E., Harich, H. -D., Illmer, T., Dorfel, S., Hannig, C. V., Koenigsmann, M., Prange-Krex, G., Tamm, I., Zeller, W., Maasberg, M., Schlag, R., Klausmann, M., Uhlig, J., Alkemper, B., Schutz, S., Tessen, H. -W., Mohr, B., Schmidt, P., Heinrich, B., Hebart, H., Seipelt, G., Zoeller, T., Heits, F., Muller-Naendrup, C., Hansen, R., Repp, R., Von Weikersthal, L. F., Schmits, R., Hessling, J., Krammer-Steiner, B., Janzen, V., Schauer, M., Gruner, M. W., Kisro, J., Denzlinger, C., Freier, W., Junghanss, C., Gorner, M., Laichinger, K., Ostermann, H., Durk, H., Hess, G., Reich, G., Matsouka, P., Pouli, A., Anagnostopoulos, A., Masszi, T., Ivanyi, J., Szomor, A., Nagler, A., Magen, H., Avivi, I., Quitt, M., Palumbo, A., Za, Tommaso, Vallisa, D., Foa, R., Bosi, A., Vacca, A., Lanza, F., Palazzo, G., Avvisati, G., Ferrara, F., Consoli, U., Cantonetti, M., Angelucci, E., Califano, C., Di Raimondo, F., Guarini, A., Musso, M., Pizzuti, M., Giuliani, N., Ardizzoia, A., Di Renzo, N., Gaidano, G., Gozzetti, A., Pitini, V., Farina, G., Centurioni, R., De Fabritiis, P., Iuliano, F., La Nasa, G., La Verde, G., Pane, F., Recine, U., La Targia, M., Mineo, G., Cangialosi, C., Fagnani, D., Federici, A., Romano, A., Specchia, G., Storti, Sergio, Bongarzoni, V., Bacigalupo, Andrea, Gobbi, M., Latte, G., Mannina, D., Capalbo, S., Jurgutis, M., Woszczyk, D., Holojda, J., Gornik, S., Pluta, A., Morawiec-Szymonik, E., Kyrcz-Krzemien, S., Homenda, W., Grosicki, S., Sulek, K., Lange, A., Kloczko, J., Starzak-Gwozdz, J., Hellmann, A., Komarnicki, M., Kuliczkowski, K., Viveiros, C., Goncalves, C., Esefyeva, N., Kaplanov, K., Volodicheva, E., Laricheva, E., Dergacheva, V., Chukavina, M., Volchenko, N., Nazarova, I., Anchukova, L., Ovanesova, E., Salogub, G., Magomedova, L., Kuznetsova, I., Osyunikhina, S., Serdyuk, O., Karyagina, E., Ivanova, V., Cernelc, S. P., Coetzee, C., Gunther, K., Moodley, D., Duran, S., Gutierrez, A. E., De Oteyza, J. P., Capote, F. J., Casanova, M., Sanchez, J. M., Rios-Herranz, E., Ibanez-Garcia, J., Herranz, M. J., Hernandez, B., Sanchez, S. S., Escalante, F., Carnicero, F., Lleonart, J. B., Gironella, M., Martinez, R., De La Guia, A. L., Palomera, L., Iglesias, R., Ramos, F. S., De La Serna, J., Sanchez, P. G., Vidal, J. B., Morfa, M. D., Beksac, T. -M., Vural, F., Aydin, Y., Unal, A., Goker, H., Bilgir, O., Guvenc, B., Turgut, M., Ozet, G. G., Ali, R., Kyselyova, M., Glushko, N., Vybyrana, R., Skrypnyk, I., Tretyak, N., Kharchevska, T., Dyagil, I., Popovs'Ka, T., Shimanskiy, V., Lysa, T., Oliynyk, H., Vilchevskaya, K., Kryachok, I., Popovych, Y., Romanyuk, N., Yushchenko, N., Kaplan, P., Rekhtman, G., Pylypenko, H., Kozlov, V., Drach, J., Harousseau, J. -L., Einsele, H., Goldschmidt, H., Facon, T., Michalet, M., Savchenko, V. G., De la Rubia, J., Cook, G., Mellqvist, U. -H., Ludwig, H., De Stefano V. (ORCID:0000-0002-5178-5827), Za T., Storti S. (ORCID:0000-0002-4374-3985), and Bacigalupo A. (ORCID:0000-0002-9119-567X)
- Abstract
Multiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and
- Published
- 2018
23. Frailty Predicts Survival and Toxicity in Newly Diagnosed Multiple Myeloma Patients Ineligible for Autologous Stem Cell Transplantation; Report of the HOVON-87/Nmsg-18 Study Group
- Author
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Stege, C A M, Van Der Holt, B, Mellqvist, U H, Levin, M D, Salomo, M, Abildgaard, N, Bos, G, Visser-Wisselaar, H, Hansson, M, Van Der Velden, A, Deenik, W, Gruber, A, Coenen, J L L M, Plesner, T, Klein, S, Tanis, B, Szatkowski, D L, Brouwer, R, Westerman, M, Leijs, M B, Sinnige, H, Haukaas, E, Van Der Hem, K, Durian, M, Mattijssen, V, Gimsing, P, Van De Donk, N W C J, Stevens-Kroef, M, Sonneveld, P, Waage, A, Zweegman, S, Internal medicine, Ethics, Law & Medical humanities, APH - Societal Participation & Health, Medical oncology, Hematology, IOO, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, CCA - Treatment and quality of life, Anatomy and neurosciences, and General practice
- Abstract
Introduction We previously reported the results of the phase III randomized HOVON-87/NMSG-18 study for Newly Diagnosed Multiple Myeloma patients not eligible for stem cell transplantation (nte-NDMM). The efficacy of melphalan, prednisolone and either thalidomide followed by thalidomide maintenance (MPT-T) versus lenalidomide followed by lenalidomide maintenance (MPR-R) was found to be comparable, being consistent across subgroups defined by age, cytogenetic risk and ISS [1]. As frailty is known to affect clinical outcome, we investigated the impact of frailty on outcome. Methods Frailty was assessed by a modification of the IMWG frailty score based on age, the Charlson Comorbidity Index (retrospectively retrieved from the list of comorbidities that were present at entry) and the WHO performance as a proxy for (instrumental) Activities of Daily Living ((i)ADL). To assess the effect of frailty on progression free survival (PFS) and OS, the logrank test was used, while the chi-squared test was used to evaluate the association of frailty with discontinuation rate and toxicity. Results All 637 eligible patients from the HOVON-87/NMSG-18 trial were included in the analysis. Median age was 73 years; 66% of patients were 80 years. A CCI of 0, 1, 2 and >=3 was found in 61, 20, 7 and 4% of patients respectively (8% unknown). The most common comorbidities were diabetes mellitus without end organ complications (12%) and myocardial infarction (6%). A WHO performance of 0, 1 and >= 2 was observed in 35, 47 and 16% respectively (3% unknown). Univariate analyses showed that older age (>80 years: HR 1.59 [95% CI 1.12-2.25]), a higher CCI (CCI >=2: HR 1.41 [95% CI 1.01-1.95]); and a poor WHO performance (WHO >=2: HR 2.05 [1.49-2.82]) were associated with an inferior OS. HR's were 1.07 [95% CI 0.82-1.40] and 1.27 [95% CI 0.98- 1.65] for age 76-80 years and WHO performance respectively. For age and the CCI the IMWG frailty score classification was used. For the WHO, scores were assigned based on the HR: WHO 0; 0 points, WHO 1; 1 point and WHO >=2; 2 points. Fit patients were defined as a proxy frailty score of 0, unfit as a score of 1 and frail as a score of >=2, comparable to the IMWG frailty score. Using this modified IMWG frailty score, 135 patients were fit (21%), 199 were unfit (31%) and 259 were frail (41%) (7% unknown). The median OS was found to be significantly different in fit versus unfit versus frail patients; 58, 55 and 46 months respectively (p=0.004). In contrast no significant difference in median PFS was found; 26, 20 and 21 months respectively (p=0.30). The inferior OS for the frail might be partly explained by higher discontinuation rate of induction therapy; 50%, versus 43% in unfit, and 34% in fit patients (p=0.011), being mainly due to excessive toxicity (25, 23 and 16% respectively). The cumulative incidence of treatment discontinuation on protocol (induction plus maintenance), corrected for death and progressive disease which were considered as competing risks, is depicted in figure 1B. Discontinuation rate at 2 years for fit, unfit, and frail patients were 48%, 48%, and 59% respectively (p=0.06). There were significantly more grade >=3 adverse events on protocol in frail and unfit patients (both 86%) as compared to fit patients (77%, p=0.039). Especially more grade >=3 infections were found in frail (28% versus 18% in unfit and 13% in fit). In contrast, frailty was not associated with hematological toxicity. Conclusion We here present a modified frailty score, using the WHO performance instead of the (i)ADL, combined with age and the CCI, that enables the identification of frail MM patients with an inferior OS, a higher discontinuation rate and a higher rate of grade >= 3 toxicity. This non-laborious modified frailty score can be easily implemented in clinical trials and allows to compare the outcome of frail patients in nte-NDMM trials, which will hopefully result in frailty-adapted therapy in clinical daily practice. (Figure Presented).
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- 2017
24. Health-related quality of life in non-transplant eligible newly diagnosed multiple myeloma patients treated with melphalan/prednisolone plus either thalidomide or lenalidomide; results of the HOVON87/NMSG18 study
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Nielsen, Lk, Stege, C, Witte, B, Holt, B, Mellqvist, U-H, Salomo, M, Levin, M-D, Hansson, M, Plesner, T, Szatkowski, D, Haukas, E, Gimsing, P, Sonneveld, P, Abildgaard, N, Waage, A, Zweegman, S, Internal medicine, Epidemiology and Data Science, APH - Methodology, Anatomy and neurosciences, General practice, Hematology, CCA - Cancer biology and immunology, CCA - Imaging and biomarkers, and CCA - Cancer Treatment and quality of life
- Subjects
humanities - Abstract
Aims: The aim is to evaluate the health-related quality of life (HRQoL) results of HOVON87/NMSG18 study (Zweegman et al., Blood 2016;127(9):1109-1116). Non-transplant eligible, newly diagnosed multiple myeloma patients were randomized between melphalan/prednisolone plus either thalidomide or lenalidomide for nine induction cycles, followed by thalidomide or lenalidomide maintenance (MPT-T or MRP-R). The study showed comparable efficacy of treatment. Methods: The validated instruments, EORTC QLQ-C30 and EORTC QLQ-MY20, were used for HRQoL measurement and were optional in the study. The patients answered the questionnaires at baseline, after 3 and 9 induction cycles and after 6 and 12 months of maintenance. Changes in HRQoL score over time during treatment and between groups were evaluated according to previously published levels of minimal important difference. Results: 613 of the total of 637 randomized patients chose to participate in the HRQoL reporting, and the baseline questionnaire was available from 553 patients (90.2%). Patient drop-out during follow-up was due to progressive disease, toxicity, death and other, and reduced the number of patients completing the therapy to 42 (15%) patients in the MPT-T and 93 (33%) in the MPR-R group. Both groups reported clinically meaningful improvement in global quality of life (QoL), physical functioning, pain, disease symptoms and insomnia. In the evaluation of difference between groups, the patients receiving MPR-R reported increasing diarrhea, better controlled pain at induction phase and increased global QoL and physical functioning during maintenance phase compared to MPT-T. The patients receiving MPT-T reported increasing constipation, better controlled pain during maintenance phase, better controlled fatigue during induction treatment and decreased insomnia compared to MPR-R. Conclusions: HRQoL during treatment is important to myeloma patients, especially when treatment efficacy of the treatment regimens is comparable. MPR-R and MPT-T both demonstrated improvements in global QoL, physical functioning and pain. Fatigue and insomnia were better controlled in the MPT-T group, which can be attributed to the thalidomide side effect of sleepiness. For interpretation of the HRQoL results patient drop-out rate must be taken in account, and we will recommend a HRQoL study design with high focus on data completeness and registration of reasons for missing data. (Figure Presented).
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- 2017
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25. International myeloma working group recommendations for the diagnosis and management of myeloma-related renal impairment
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Dimopoulos, M.A. Sonneveld, P. Leung, N. Merlini, G. Ludwig, H. Kastritis, E. Goldschmidt, H. Joshua, D. Orlowski, R.Z. Powles, R. Vesole, D.H. Garderet, L. Einsele, H. Palumbo, A. Cavo, M. Richardson, P.G. Moreau, P. Miguel, J.S. Vincent Rajkumar, S. Durie, B.G.M. Terpos, E. Abildgaard, N. Abonour, R. Alsina, M. Anderson, K.C. Attal, M. Avet-Loiseau, H. Badros, A. Bahlis, N.J. Barlogie, B. Bataille, R. Beksaç, M. Belch, A. Ben-Yehuda, D. Bensinger, B. Leif Bergsagel, P. Bhutani, M. Bird, J. Bladé, J. Broijl, A. Boccadoro, M. Caers, J. Chanan-Khan, A. Chari, A. Chen, W.M. Chesi, M. Anthony Child, J. Chim, C.S. Chng, W.-J. Comenzo, R. Cook, G. Crowley, J. Crusoe, E. Dalton, W. Lee Moffitt, H. Davies, F. de la Rubia, J. de Souza, C. Delforge, M. Dhodapkar, M. Dispenzieri, A. Drach, J. Drake, M. Du, J. Dytfeld, D. Facon, T. Fantl, D. Fermand, J.-P. Fernández de Larrea, C. Fonseca, R. Gahrton, G. Garćia-Sanz, R. Gasparetto, C. Gertz, M. Ghobrial, I. Gibson, J. Gimsing, P. Giralt, S. Gu, J. Hajek, R. Hardan, I. Hari, P. Hata, H. Hattori, Y. Heffner, T. Hillengass, J. Ho, J. Hoering, A. Hoffman, J.E. Hou, J. Huang, J. Hungria, V. Ida, S. Jagannath, S. Jakubowiak, A.J. Johnsen, H.E. Jurczyszyn, A. Kaiser, M. Kaufman, J. Kawano, M. Korde, N. Kovacs, E. Krishnan, A. Kristinsson, S. Kröger, N. Kumar, S. Kyle, R.A. Kyriacou, C. Lacy, M. Lahuerta, J.J. Landgren, O. Larocca, A. Laubach, J. da Costa, F.L. Lee, J.-H. Leiba, M. Leleu, X. Lentzsch, S. Lokhorst, H. Lonial, S. Lu, J. Mahindra, A. Maiolino, A. Manasanch, E.E. Mark, T. Mateos, M.-V. Mazumder, A. McCarthy, P. Mehta, J. Mellqvist, U.-H. Mikhael, J. Morgan, G. Munshi, N. Nahi, H. Nawarawong, W. Niesvizky, R. Nouel, A. Novis, Y. Ocio, E. O'Dwyer, M. O'Gorman, P. Orfao, A. Otero, P.R. Paiva, B. Pavlovsky, S. Pilarski, L. Pratt, G. Qui, L. Raje, N. Reece, D. Reiman, A. Remaggi, G. Richter, J. Serra, E.R. Morales, A.R. Romeril, K.R. Roodman, D. Rosiñol, L. Rossi, A. Roussel, M. Russell, S. Schjesvold, F. Schots, R. Sevcikova, S. Sezer, O. Shah, J.J. Shimizu, K. Shustik, C. Siegel, D. Singhal, S. Spencer, A. Stadtmauer, E. Stewart, K. Tan, D. Terragna, C. Tosi, P. Tricot, G. Turesson, I. Usmani, S. Van Camp, B. Van de Donk, N. Van Ness, B. Van Riet, I. Broek, I.V. Vanderkerken, K. Vescio, R. Vij, R. Voorhees, P. Waage, A. Wang, M. Weber, D. Weiss, B.M. Westin, J. Wheatley, K. Zamagni, E. Zonder, J. Zweegman, S.
- Abstract
Purpose: The aim of the International Myeloma Working Group was to develop practical recommendations for the diagnosis and management of multiple myeloma–related renal impairment (RI). Methods: Recommendations were based on published data through December 2015, and were developed using the system developed by the Grading of Recommendation, Assessment, Development, and Evaluation Working Group. Recommendations: All patients with myeloma at diagnosis and at disease assessment should have serum creatinine, estimated glomerular filtration rate, and electrolytes measurements as well as free light chain, if available, and urine electrophoresis of a sample from a 24-hour urine collection (grade A). The Chronic Kidney Disease Epidemiology Collaboration, preferably, or the Modification of Diet in Renal Disease formula should be used for the evaluation of estimated glomerular filtration rate in patients with stabilized serum creatinine (grade A). International Myeloma Working Group criteria for renal reversibility should be used (grade B). For the management of RI in patients with multiple myeloma, high fluid intake is indicated along with antimyeloma therapy (grade B). The use of high-cutoff hemodialysis membranes in combination with antimyeloma therapy can be considered (grade B). Bortezomib-based regimens remain the cornerstone of the management of myeloma-related RI (grade A). High-dose dexamethasone should be administered at least for the first month of therapy (grade B). Thalidomide is effective in patients with myeloma with RI, and no dose modifications are needed (grade B). Lenalidomide is effective and safe, mainly in patients with mild to moderate RI (grade B); for patients with severe RI or on dialysis, lena-lidomide should be given with close monitoring for hematologic toxicity (grade B) with dose reduction as needed. High-dose therapy with autologous stem cell transplantation (with melphalan 100 mg/m2 to 140 mg/m2) is feasible in patients with RI (grade C). Carfilzomib can be safely administered to patients with creatinine clearance > 15 mL/min, whereas ixazomib in combination with lenalidomide and dex-amethasone can be safely administered to patients with creatinine clearance > 30 mL/min (grade A). © 2016 by American Society of Clinical Oncology.
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- 2016
26. Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network
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Ludwig, H, primary, Delforge, M, additional, Facon, T, additional, Einsele, H, additional, Gay, F, additional, Moreau, P, additional, Avet-Loiseau, H, additional, Boccadoro, M, additional, Hajek, R, additional, Mohty, M, additional, Cavo, M, additional, Dimopoulos, M A, additional, San-Miguel, J F, additional, Terpos, E, additional, Zweegman, S, additional, Garderet, L, additional, Mateos, M-V, additional, Cook, G, additional, Leleu, X, additional, Goldschmidt, H, additional, Jackson, G, additional, Kaiser, M, additional, Weisel, K, additional, van de Donk, N W C J, additional, Waage, A, additional, Beksac, M, additional, Mellqvist, U H, additional, Engelhardt, M, additional, Caers, J, additional, Driessen, C, additional, and Sonneveld, P, additional
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- 2017
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27. Global myeloma research clusters, output, and citations: A bibliometric mapping and clustering analysis
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Andersen, J.P. Bøgsted, M. Dybkær, K. Mellqvist, U.-H. Morgan, G.J. Goldschmidt, H. Dimopoulos, M.A. Einsele, H. San Miguel, J. Palumbo, A. Sonneveld, P. Johnsen, H.E.
- Abstract
Background: International collaborative research is a mechanism for improving the development of dis-ease- specific therapies and for improving health at the population level. However, limited data are available to assess the trends in research output related to orphan diseases. Methods and Findings: We used bibliometric mapping and clustering methods to illustrate the level of fragmentation in myeloma research and the development of collaborative efforts. Publication data from Thomson Reuters Web of Science were retrieved for 2005-2009 and followed until 2013. We created a database of multiple myeloma publications, and we analysed impact and coauthorship density to identify scientific collaborations, developments, and international key players over time. The global annual publication volume for studies on multiple myeloma increased from 1,144 in 2005 to 1,628 in 2009, which represents a 43% increase. This increase is high compared to the 24% and 14% increases observed for lymphoma and leukaemia. The major proportion (>90% of publications) was from the US and EU over the study period. The output and impact in terms of citations, identified several successful groups with a large number of intra-cluster collaborations in the US and EU. The US-based myeloma clusters clearly stand out as the most productive and highly cited, and the European Myeloma Network members exhibited a doubling of collaborative publications from 2005 to 2009, still increasing up to 2013. Conclusion and Perspective: Multiple myeloma research output has increased substantially in the past decade. The fragmented European myeloma research activities based on national or regional groups are progressing, but they require a broad range of targeted research investments to improve multiple myeloma health care. © 2015 Andersen et al.
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- 2015
28. Encouraging Preliminary Data in Ongoing Open-Label Phase 1/2 Study of Safety and Efficacy of Melflufen and *Dexamethasone for Patients with Relapsed and Relapsed-Refractory Multiple Myeloma
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Magarotto, V., Sonneveld, P., Voorhees, P., Paba-Prada, C., Plesner, T., Mellqvist, U. H., Byrne, C., Harmenberg, J., Nordstrom, E., Palumbo, A., and Richardson, P.
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- 2015
29. Outcome of AL amyloidosis after high-dose melphalan and autologous stem cell transplantation in Sweden, long-term results from all patients treated in 1994-2009.
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Rosengren, Sara, Mellqvist, U-H, Nahi, H, Forsberg, K, Lenhoff, S, Strömberg, O, Ahlberg, L, Linder, O, Carlson, Kristina, Rosengren, Sara, Mellqvist, U-H, Nahi, H, Forsberg, K, Lenhoff, S, Strömberg, O, Ahlberg, L, Linder, O, and Carlson, Kristina
- Abstract
High-dose melphalan and autologous stem cell transplantation (HDM/ASCT) is widely used in immunoglobulin light chain (AL) amyloidosis, but the benefit is debated mainly because of the high treatment-related mortality (24% in a randomised study comparing HDM/ASCT with oral melphalan/dexamethasone). We report here on the long-term outcome of all patients treated with HDM/ASCT for AL amyloidosis in Sweden between 1994 and 2009. Seventy-two patients were treated at eight Swedish centres. Median follow-up was 67.5 months. At least partial response (organ or haematological) was seen in 64% of the patients. Median overall survival was 98 months or 8.2 years, with 5-year survival 63.9% and 10-year survival 43.4%. In patients with cardiac involvement or multiple organ involvement, survival was significantly shorter, median overall survival 49 and 56 months, respectively. All mortality within 100 days from ASCT was 12.5% for all patients and 17.2% in the patients with cardiac involvement. For patients treated in the earlier time period (1994-2001), 100-day mortality was 23.8% compared with 7.8% in the later period (2002-2009). In conclusion, long survival times can be achieved in patients with AL amyloidosis treated with HDM/ASCT, also in smaller centres. Early mortality is high, but with a decreasing trend over time.
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- 2016
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30. New drugs and novel mechanisms of action in multiple myeloma in 2013: A report from the International Myeloma Working Group (IMWG)
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Ocio, E.M. Richardson, P.G. Rajkumar, S.V. Palumbo, A. Mateos, M.V. Orlowski, R. Kumar, S. Usmani, S. Roodman, D. Niesvizky, R. Einsele, H. Anderson, K.C. Dimopoulos, M.A. Avet-Loiseau, H. Mellqvist, U.-H. Turesson, I. Merlini, G. Schots, R. Mccarthy, P. Bergsagel, L. Chim, C.S. Lahuerta, J.J. Shah, J. Reiman, A. Mikhael, J. Zweegman, S. Lonial, S. Comenzo, R. Chng, W.J. Moreau, P. Sonneveld, P. Ludwig, H. Durie, B.G.M. Miguel, J.F.S.
- Abstract
Treatment in medical oncology is gradually shifting from the use of nonspecific chemotherapeutic agents toward an era of novel targeted therapy in which drugs and their combinations target specific aspects of the biology of tumor cells. Multiple myeloma (MM) has become one of the best examples in this regard, reflected in the identification of new pathogenic mechanisms, together with the development of novel drugs that are being explored from the preclinical setting to the early phases of clinical development. We review the biological rationale for the use of the most important new agents for treating MM and summarize their clinical activity in an increasingly busy field. First, we discuss data from already approved and active agents (including second- and third-generation proteasome inhibitors (PIs), immunomodulatory agents and alkylators). Next, we focus on agents with novel mechanisms of action, such as monoclonal antibodies (MoAbs), cell cycle-specific drugs, deacetylase inhibitors, agents acting on the unfolded protein response, signaling transduction pathway inhibitors and kinase inhibitors. Among this plethora of new agents or mechanisms, some are specially promising: anti-CD38 MoAb, such as daratumumab, are the first antibodies with clinical activity as single agents in MM. Moreover, the kinesin spindle protein inhibitor Arry-520 is effective in monotherapy as well as in combination with dexamethasone in heavily pretreated patients. Immunotherapy against MM is also being explored, and probably the most attractive example of this approach is the combination of the anti-CS1 MoAb elotuzumab with lenalidomide and dexamethasone, which has produced exciting results in the relapsed/refractory setting. © 2014 Macmillan Publishers Limited.
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- 2014
31. An ongoing open-label phase 1/2a study of the safety and efficacy of melphalan-flufenamide (melflufen) and dexamethasone combination for patients with relapsed and relapsed-refractory multiple myeloma
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Mellqvist, U-H, Paba-Prada, C, Palumbo, A, Plesner, Torben, Sonneveld, P, Voorhees, P, Byrne, C, Harmenberg, J, Nordström, E, and Richardson, P.
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- 2014
32. Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT.:A phase-2 trial
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Gimsing, P, Hjertner, Ø, Abildgaard, N, Andersen, N F, Gedde-Dahl, Tobias, Gregersen, H, Klausen, T W, Mellqvist, U-H, Linder, O, Lindås, R, Tøffner Clausen, N, Lenhoff, S, Gimsing, P, Hjertner, Ø, Abildgaard, N, Andersen, N F, Gedde-Dahl, Tobias, Gregersen, H, Klausen, T W, Mellqvist, U-H, Linder, O, Lindås, R, Tøffner Clausen, N, and Lenhoff, S
- Abstract
Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared with the initial ASCT. Bortezomib-HDM conditioning combo was feasible, and toxicity was as expected for patients treated with bortezomib and ASCT. In conclusion, in bortezomib-naïve patients treated at first relapse with salvage ASCT including bortezomib, PSF and TNT did not differ significantly from initial ASCT and median OS was almost 5.5 years with acceptable toxicity. A recent prospective randomized study confirms salvage ASCT to be an effective treatment.
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- 2015
33. Plasma cell leukemia: Consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group
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Fernández De Larrea, C. Kyle, R.A. Durie, B.G.M. Ludwig, H. Usmani, S. Vesole, D.H. Hajek, R. San Miguel, J.F. Sezer, O. Sonneveld, P. Kumar, S.K. Mahindra, A. Comenzo, R. Palumbo, A. Mazumber, A. Anderson, K.C. Richardson, P.G. Badros, A.Z. Caers, J. Cavo, M. Leleu, X. Dimopoulos, M.A. Chim, C.S. Schots, R. Noeul, A. Fantl, D. Mellqvist, U.-H. Landgren, O. Chanan-Khan, A. Moreau, P. Fonseca, R. Merlini, G. Lahuerta, J.J. Bladé, J. Orlowski, R.Z. Shah, J.J.
- Abstract
Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathological entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥20%) and absolute number (≥2 × 10 9/l) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be re-examined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem cell transplantation if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL. © 2013 Macmillan Publishers Limited All rights reserved.
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- 2013
34. Management of relapsed multiple myeloma: recommendations of the International Myeloma Working Group
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Laubach, J, primary, Garderet, L, additional, Mahindra, A, additional, Gahrton, G, additional, Caers, J, additional, Sezer, O, additional, Voorhees, P, additional, Leleu, X, additional, Johnsen, H E, additional, Streetly, M, additional, Jurczyszyn, A, additional, Ludwig, H, additional, Mellqvist, U-H, additional, Chng, W-J, additional, Pilarski, L, additional, Einsele, H, additional, Hou, J, additional, Turesson, I, additional, Zamagni, E, additional, Chim, C S, additional, Mazumder, A, additional, Westin, J, additional, Lu, J, additional, Reiman, T, additional, Kristinsson, S, additional, Joshua, D, additional, Roussel, M, additional, O'Gorman, P, additional, Terpos, E, additional, McCarthy, P, additional, Dimopoulos, M, additional, Moreau, P, additional, Orlowski, R Z, additional, Miguel, J S, additional, Anderson, K C, additional, Palumbo, A, additional, Kumar, S, additional, Rajkumar, V, additional, Durie, B, additional, and Richardson, P G, additional
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- 2015
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35. THE REVII TRIAL : LENALIDOMIDE AND DEXAMETHASONE AS SECOND LINE TREATMENT IN MYELOMA FOLLOWED BY EXTENDED LENALIDOMID VS LEN/DEX
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Lund, J., Gruber, A., Lauri, B., Blimark, C., Swedin, A., Hansson, M., Forsberg, Karin, Ahlberg, L., Carlsson, C., Waage, A., Gimsing, P., Vangsted, A. J., Frolund, U., Hardling, M., Mellqvist, U. H., Nahi, H., Lund, J., Gruber, A., Lauri, B., Blimark, C., Swedin, A., Hansson, M., Forsberg, Karin, Ahlberg, L., Carlsson, C., Waage, A., Gimsing, P., Vangsted, A. J., Frolund, U., Hardling, M., Mellqvist, U. H., and Nahi, H.
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- 2014
36. Intensive therapy for multiple myeloma in patients younger than 60 years.Long-term results focusing on the effect of the degree of response on survivaland relapse pattern after transplantation
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Lenhoff, S, Hjort, M, Toresson, I, Westin, J, Gimsing, P, Wisloff, F, Ahlberg, L, Carlson, K, Christiansen, I, Dahl, I M, Forsberg, K, Brinch, L, Hammerstrom, J, Johnsen, Hans Erik, knudsen, L M, Linder, O, Mellqvist, U H, Nesthus, I, and Nielsen, Johan Lanng
- Abstract
Udgivelsesdato: september
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- 2006
37. Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients
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Blimark, C., primary, Holmberg, E., additional, Mellqvist, U.-H., additional, Landgren, O., additional, Bjorkholm, M., additional, Hultcrantz, M., additional, Kjellander, C., additional, Turesson, I., additional, and Kristinsson, S. Y., additional
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- 2014
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38. Impact of age on survival after intensive therapy for multiple myeloma : A population-based study by the Nordic Myeloma Study Group
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Lenhoff, S., Hjorth, M., Westin, J., Brinch, L., Backstrom, B., Carlson, K., Christiansen, I., Dahl, I.M., Gimsing, P., Hammerstrom, J., Johnsen, H.E., Juliusson, Gunnar, Linder, O., Mellqvist, U.-H., Nesthus, I., Nielsen, J.L., Tangen, J.M., Turesson, I., Lenhoff, S., Hjorth, M., Westin, J., Brinch, L., Backstrom, B., Carlson, K., Christiansen, I., Dahl, I.M., Gimsing, P., Hammerstrom, J., Johnsen, H.E., Juliusson, Gunnar, Linder, O., Mellqvist, U.-H., Nesthus, I., Nielsen, J.L., Tangen, J.M., and Turesson, I.
- Abstract
The value of intensive therapy, including autologous stem cell transplantation, in newly diagnosed myeloma patients >60 years is not clear. We evaluated the impact of age (<60 years vs. 60-64 years) on survival in a prospective, population-based setting and compared survival with conventionally treated historic controls. The prospective population comprised 452 patients registered between 1998 and 2000. Of these, 414 received intensive therapy. The historic population, derived from our most recent population-based study on conventional therapy, comprised 281 patients. Of these, 243 fulfilled our eligibility criteria for intensive therapy. For patients undergoing intensive therapy it was found that two factors, beta-2-microglobulin and age <60 years vs. 60-64 years, had independent prognostic impact on survival. However, compared with the historic controls a survival advantage was found both for patients <60 (median 66 months vs. 43 months, P < 0.001) and 60-64 years (median 50 months vs. 27 months, P = 0.001). We conclude that in a population-based setting higher age adversely influences outcome after intensive therapy. Our results indicate that intensive therapy prolongs survival also at age 60-64 years but with less superiority than in younger patients. © 2006 Blackwell Publishing Ltd.
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- 2006
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39. Monoclonal gammopathy of undetermined significance and risk of infections: a population-based study
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Kristinsson, S. Y., primary, Tang, M., additional, Pfeiffer, R. M., additional, Bjorkholm, M., additional, Goldin, L. R., additional, Blimark, C., additional, Mellqvist, U.-H., additional, Wahlin, A., additional, Turesson, I., additional, and Landgren, O., additional
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- 2011
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40. Patterns of survival and causes of death following a diagnosis of monoclonal gammopathy of undetermined significance: a population-based study
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Kristinsson, S. Y., primary, Bjorkholm, M., additional, Andersson, T. M-L, additional, Eloranta, S., additional, Dickman, P. W., additional, Goldin, L. R., additional, Blimark, C., additional, Mellqvist, U.-H., additional, Wahlin, A., additional, Turesson, I., additional, and Landgren, O., additional
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- 2009
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41. NK cell-mediated killing of AML blasts: role of histamine, monocytes and reactive oxygen metabolites
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Brune, M., primary, Hansson, M., additional, Mellqvist, U.-H., additional, Hermodsson, S., additional, and Hellstrand, K., additional
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- 2009
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42. A father and his son with systemic AL amyloidosis
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Enqvist, S., primary, Mellqvist, U.-H., additional, Molne, J., additional, Sletten, K., additional, Murphy, C., additional, Solomon, A., additional, Stevens, F. J, additional, and Westermark, P., additional
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- 2009
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43. Clinical experience with recombinant factor VIIa in patients with thrombocytopenia
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Kristensen, J, Killander, A, Hippe, E, Helleberg, C, Ellegaard, J, Holm, M, Kutti, J, Mellqvist, U-H, Johansson, J E, Glazer, S, Hedner, U, Kristensen, J, Killander, A, Hippe, E, Helleberg, C, Ellegaard, J, Holm, M, Kutti, J, Mellqvist, U-H, Johansson, J E, Glazer, S, and Hedner, U
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- 1996
44. Histamine dihydrochloride (Maxamine™), interleukin-2 (IL-2) and interferon-α (IFN-α) in multiple myeloma
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Mellqvist, U.-H., primary, Wallhult, E., additional, Hellstrand, K., additional, Nilsson, B., additional, and Brune, M., additional
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- 1999
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45. Histamine in cancer immunotherapy
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Hellstrand, K., primary, Hermodsson, S., additional, Brune, M., additional, Naredi, P., additional, Carneskog, J., additional, and Mellqvist, U.-H., additional
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- 1997
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46. Histamine Protects T Cells and Natural Killer Cells Against Oxidative Stress
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Hansson, M., Hermodsson, S., Brune, M., Mellqvist, U. H., Naredi, P., Betten, A., Gehlsen, K.R., and Hellstrand, K.
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- 1999
47. NK cell-mediated killing of AML blasts: role of histamine, monocytes and reactive oxygen metabolites.
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Brune, M., Hansson, M., Mellqvist, U.-H., Hermodsson, S., and Hellstrand, K.
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- 1996
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48. Autologous haematopoietic stem-cell transplantation versus bortezomib-melphalan-prednisone, with or without bortezomib-lenalidomide-dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95)
- Author
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Michele Cavo, Francesca Gay, Meral Beksac, Lucia Pantani, Maria Teresa Petrucci, Meletios A Dimopoulos, Luca Dozza, Bronno van der Holt, Sonja Zweegman, Stefania Oliva, Vincent H J van der Velden, Elena Zamagni, Giuseppe A Palumbo, Francesca Patriarca, Vittorio Montefusco, Monica Galli, Vladimir Maisnar, Barbara Gamberi, Markus Hansson, Angelo Belotti, Ludek Pour, Paula Ypma, Mariella Grasso, Alexsandra Croockewit, Stelvio Ballanti, Massimo Offidani, Iolanda D Vincelli, Renato Zambello, Anna Marina Liberati, Niels Frost Andersen, Annemiek Broijl, Rossella Troia, Anna Pascarella, Giulia Benevolo, Mark-David Levin, Gerard Bos, Heinz Ludwig, Sara Aquino, Anna Maria Morelli, Ka Lung Wu, Rinske Boersma, Roman Hajek, Marc Durian, Peter A von dem Borne, Tommaso Caravita di Toritto, Thilo Zander, Christoph Driessen, Giorgina Specchia, Anders Waage, Peter Gimsing, Ulf-Henrik Mellqvist, Marinus van Marwijk Kooy, Monique Minnema, Caroline Mandigers, Anna Maria Cafro, Angelo Palmas, Susanna Carvalho, Andrew Spencer, Mario Boccadoro, Pieter Sonneveld, Hematology, CCA - Cancer Treatment and quality of life, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Interne Geneeskunde, MUMC+: MA Hematologie (9), Immunology, Cavo M., Gay F., Beksac M., Pantani L., Petrucci M.T., Dimopoulos M.A., Dozza L., van der Holt B., Zweegman S., Oliva S., van der Velden V.H.J., Zamagni E., Palumbo G.A., Patriarca F., Montefusco V., Galli M., Maisnar V., Gamberi B., Hansson M., Belotti A., Pour L., Ypma P., Grasso M., Croockewit A., Ballanti S., Offidani M., Vincelli I.D., Zambello R., Liberati A.M., Andersen N.F., Broijl A., Troia R., Pascarella A., Benevolo G., Levin M.-D., Bos G., Ludwig H., Aquino S., Morelli A.M., Wu K.L., Boersma R., Hajek R., Durian M., von dem Borne P.A., Caravita di Toritto T., Zander T., Specchia G., Waage A., Gimsing P., Mellqvist U.-H., van Marwijk Kooy M., Minnema M., Mandigers C., Cafro A.M., Palmas A., Carvalho S., Spencer A., Boccadoro M., and Sonneveld P.
- Subjects
Male ,Melphalan ,Gastrointestinal Diseases ,multiple myeloma, ASCT, consolidation therapy, EMN02/HO95 ,Dexamethasone ,Bortezomib ,0302 clinical medicine ,Maintenance therapy ,Antineoplastic Combined Chemotherapy Protocols ,Medicine ,Lenalidomide ,Multiple myeloma ,education.field_of_study ,Hematopoietic Stem Cell Transplantation ,Hematology ,Middle Aged ,daratumumab ,Myeloma Proteins ,SINGLE ,030220 oncology & carcinogenesis ,Administration, Intravenous ,Female ,Multiple Myeloma ,medicine.drug ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,medicine.medical_specialty ,Neutropenia ,Injections, Subcutaneous ,Population ,Infections ,Transplantation, Autologous ,Disease-Free Survival ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,Internal medicine ,Humans ,education ,Neoplasm Staging ,Performance status ,business.industry ,DELETION ,medicine.disease ,Thrombocytopenia ,Consolidation Chemotherapy ,Transplantation ,Prednisone ,business ,Plasmacytoma ,DARATUMUMAB ,030215 immunology - Abstract
Background The emergence of highly active novel agents has led some to question the role of autologous haematopoietic stem-cell transplantation (HSCT) and subsequent consolidation therapy in newly diagnosed multiple myeloma. We therefore compared autologous HSCT with bortezomib-melphalan-prednisone (VMP) as intensification therapy, and bortezomib-lenalidomide-dexamethasone (VRD) consolidation therapy with no consolidation.Methods In this randomised, open-label, phase 3 study we recruited previously untreated patients with multiple myeloma at 172 academic and community practice centres of the European Myeloma Network. Eligible patients were aged 18-65 years, had symptomatic multiple myeloma stage 1-3 according to the International Staging System (I S S), measurable disease (serum M protein >10 g/L or urine M protein >200 mg in 24 h or abnormal free light chain [FLC] ratio with involved FLC >100 mg/L, or proven plasmacytoma by biopsy), and WHO performance status grade 0-2 (grade 3 was allowed if secondary to myeloma). Patients were first randomly assigned (1:1) to receive either four 42-day cycles of bortezomib (1.3 mg/m 2 administered intravenously or subcutaneously on days 1, 4, 8, 11, 22, 25, 29, and 32) combined with melphalan (9 mg/m(2) administered orally on days 1-4) and prednisone (60 mg/m(2) administered orally on days 1-4) or autologous HSCT after high-dose melphalan (200 mg/m(2)), stratified by site and ISS disease stage. In centres with a double HS CT policy, the first randomisation (1:1:1) was to VMP or single or double HSCT. Afterwards, a second randomisation assigned patients to receive two 28-day cycles of consolidation therapy with bortezomib (1.3 mg/m(2)either intravenously or subcutaneously on days 1, 4, 8, and 11), lenalidomide (25 mg orally on days 1-21), and dexamethasone (20 mg orally on days 1, 2, 4, 5, 8, 9, 11, and 12) or no consolidation; both groups received lenalidomide maintenance therapy (10 mg orally on days 1-21 of a 28-day cycle). The primary outcomes were progression-free survival from the first and second randomisations, analysed in the intention-to-treat population, which included all patients who underwent each randomisation. All patients who received at least one dose of study drugs were included in the safety analyses. This study is registered with the EU Clinical Trials Register (EudraCT 2009-017903-28) and ClinicalTrials.gov (NCT01208766), and has completed recruitment.Findings Between Feb 25, 2011, and April 3, 2014, 1503 patients were enrolled. 1197 patients were eligible for the first randomisation, of whom 702 were assigned to autologous HSCT and 495 to VMP; 877 patients who were eligible for the first randomisation underwent the second randomisation to VRD consolidation (n=449) or no consolidation (n=428). The data cutoff date for the current analysis was Nov 26, 2018. At a median follow-up of 60.3 months (IQR 52. 2-67. 6), median progression-free survival was significantly improved with autologous HSCT compared with VMP (56.7 months [95% CI 49.3-64.5] vs 41.9 months [37.5-46.9]; hazard ratio [HR] 0.73, 0.62-0.85; p=0.0001). For the second randomisation, the number of events of progression or death at data cutoff was lower than that preplanned for the final analysis; therefore, the results from the second protocol-specified interim analysis, when 66% of events were reached, are reported (data cutoff Jan 18, 2018). At a median follow-up of 42.1 months (IQR 32.3-49.2), consolidation therapy with VRD significantly improved median progression-free survival compared with no consolidation (58.9 months [54.0-not estimable] vs 45.5 months [39.5-58.4]; HR 0.77, 0.63-0.95; p=0.014). The most common grade >= 3 adverse events in the autologous HSCT group compared to the VMP group included neutropenia (513 [79%] of 652 patients vs 137 [29%] of 472 patients), thrombocytopenia (541 [83%] vs 74 [16%]), gastrointestinal disorders (80 [12%] vs 25 [5%]), and infections (192 [30%] vs 18 [4%]). 239 (34%) of 702 patients in the autologous HSCT group and 135 (27%) of 495 in the VMP group had at least one serious adverse event. Infection was the most common serious adverse event in each of the treatment groups (206 [56%] of 368 and 70 [37%] of 189). 38 (12%) of 311 deaths from first randomisation were likely to be treatment related: 26 (68%) in the autologous HSCT group and 12 (32%) in the VMP group, most frequently due to infections (eight [21%]), cardiac events (six [16%]), and second primary malignancies (20 [53%]).Interpretation This study supports the use of autologous HSCT as intensification therapy and the use of consolidation therapy in patients with newly diagnosed multiple myeloma, even in the era of novel agents. The role of high-dose chemotherapy needs to be reassessed in future studies, in particular in patients with undetectable minimal residual disease after four-drug induction regimens including a monoclonal antiboby combined with an immunomodulatory agent and a proteasome inhibitor plus dexamethasone. Copyright (C) 2020 Elsevier Ltd. All rights reserved.
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- 2020
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49. Treatment of relapsed and refractory multiple myeloma: recommendations from the International Myeloma Working Group
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Mario Boccadoro, Peter Leif Bergsagel, Noopur Raje, Xavier Leleu, Cristina João, Joseph R. Mikhael, Monika Engelhardt, Brian G.M. Durie, Sarah A. Holstein, Heinz Ludwig, Parameswaran Hari, Gordon Cook, Anders Waage, Maria-Victoria Mateos, Ulf-Henrik Mellqvist, Hareth Nahi, Faith E. Davies, Jian Hou, Angelo Maiolino, Saad Z. Usmani, Nizar J. Bahlis, Wee Joo Chng, Sigurdur Y. Kristinsson, Fernando Leal da Costa, Hartmut Goldschmidt, Evangelos Terpos, Pieter Sonneveld, Dominik Dytfeld, Artur Jurczyszyn, Michele Cavo, Fredrik Schjesvold, Meletios A. Dimopoulos, Jacob P. Laubach, Jesus San Miguel, Kwee Yong, Elena Zamagni, Orhan Sezer, Martin Kaiser, Surbhi Sidana, Vania Hungria, Meral Beksac, Enrique M. Ocio, Nikhil C. Munshi, Kenneth C. Anderson, Katja Weisel, Thierry Facon, Annette Juul Vangsted, Christoph Driessen, Hermann Einsele, Luciano J. Costa, Shaji Kumar, Paul G. Richardson, Philippe Moreau, Jesus G. Berdeja, Roman Hájek, Thomas G. Martin, Sagar Lonial, David H. Vesole, Rafael Fonseca, Suzanne Lentzsch, Eloisa Riva, Simon J. Harrison, Hang Quach, Rachid Baz, S. Vincent Rajkumar, Niels W.C.J. van de Donk, Joan Bladé, Jean-Luc Harousseau, Sonja Zweegman, Moreau P., Kumar S.K., San Miguel J., Davies F., Zamagni E., Bahlis N., Ludwig H., Mikhael J., Terpos E., Schjesvold F., Martin T., Yong K., Durie B.G.M., Facon T., Jurczyszyn A., Sidana S., Raje N., van de Donk N., Lonial S., Cavo M., Kristinsson S.Y., Lentzsch S., Hajek R., Anderson K.C., Joao C., Einsele H., Sonneveld P., Engelhardt M., Fonseca R., Vangsted A., Weisel K., Baz R., Hungria V., Berdeja J.G., Leal da Costa F., Maiolino A., Waage A., Vesole D.H., Ocio E.M., Quach H., Driessen C., Blade J., Leleu X., Riva E., Bergsagel P.L., Hou J., Chng W.J., Mellqvist U.-H., Dytfeld D., Harousseau J.-L., Goldschmidt H., Laubach J., Munshi N.C., Gay F., Beksac M., Costa L.J., Kaiser M., Hari P., Boccadoro M., Usmani S.Z., Zweegman S., Holstein S., Sezer O., Harrison S., Nahi H., Cook G., Mateos M.-V., Rajkumar S.V., Dimopoulos M.A., Richardson P.G., and Hematology
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medicine.medical_specialty ,Line of therapy ,Drug Resistance ,Salvage therapy ,Antineoplastic Agents ,030204 cardiovascular system & hematology ,Antineoplastic Agent ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Humans ,Intensive care medicine ,Multiple myeloma ,Salvage Therapy ,Hematology ,business.industry ,Cancer ,Refractory Multiple Myeloma ,medicine.disease ,Drug access ,Clinical research ,Neoplasm Recurrence ,Oncology ,Local ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Neoplasm ,Multiple Myeloma ,Neoplasm Recurrence, Local ,business ,Human - Abstract
This Policy Review presents the International Myeloma Working Group's clinical practice recommendations for the treatment of relapsed and refractory multiple myeloma. Based on the results of phase 2 and phase 3 trials, these recommendations are proposed for the treatment of patients with relapsed and refractory disease who have received one previous line of therapy, and for patients with relapsed and refractory multiple myeloma who have received two or more previous lines of therapy. These recommendations integrate the issue of drug access in both low-income and middle-income countries and in high-income countries to help guide real-world practice and thus improve patient outcomes.
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- 2021
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50. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study
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Mohamad Mohty, Evangelos Terpos, Maria-Victoria Mateos, Michele Cavo, Sandra Lejniece, Meral Beksac, Mohamed Amine Bekadja, Wojciech Legiec, Meletios Dimopoulos, Svetlana Stankovic, Maria Soledad Durán, Valerio De Stefano, Alessandro Corso, Yulia Kochkareva, Edward Laane, Christian Berthou, Hans Salwender, Zvenyslava Masliak, Valdas Pečeliūnas, Wolfgang Willenbacher, João Silva, Vernon Louw, Damir Nemet, Zita Borbényi, Uri Abadi, Robert Schou Pedersen, Peter Černelč, Anna Potamianou, Catherine Couturier, Caroline Feys, Florence Thoret-Bauchet, Mario Boccadoro, Mohamed Bekadja, Rose-Marie Hamladji, Hocine Ait Ali, Selma Hamdi, Hadj Touhami, Nourredine Sidi Mansour, Werner Linkesch, Robert Shou Pedersen, Niels Abildgaard, Marju Hein, Jean Richard Eveillard, Abderrazak el Yamani, Philippe Moreau, Laurence Sanhes, Gérard Lepeu, Kamel Laribi, Eric Jourdan, Olivier Fitoussi, Olivier Allangba, Joël Fleury, Martine Escoffre, Riad Benramdane, Guillaume Cartron, Gérard Dine, Eric Legouffe, Hanns-Detlev Harich, Thomas Illmer, Steffen Dörfel, Carla Verena Hannig, Michael Koenigsmann, Gabriele Prange-Krex, Ingo Tamm, Wolfgang Zeller, Michael Maasberg, Rudolf Schlag, Martine Klausmann, Jens Uhlig, Burkhard Alkemper, Stefan Schütz, Hans-Werner Tessen, Benno Mohr, Peter Schmidt, Bernhard Heinrich, Holger Hebart, Gernot Seipelt, Thomas Zoeller, Frank Heits, Clemens Müller-Naendrup, Richard Hansen, Roland Repp, Ludwig Fischer Von Weikersthal, Rudolf Schmits, Jörg Heßling, B. Krammer-Steiner, Viktor Janzen, Michael Schauer, Marcus W. Grüner, Jens Kisro, Claudio Denzlinger, Werner Freier, Christian Junghanss, Martin Görner, Katharina Laichinger, Helmut Ostermann, Heinz Dürk, Georg Hess, Gernot Reich, Panagiota Matsouka, Anastasia Pouli, Achilles Anagnostopoulos, Tamas Masszi, Janos Ivanyi, Arpad Szomor, Arnon Nagler, Hila Magen, Irit Avivi, Miriam Quitt, Antonio Palumbo, Tommaso Za, Daniele Vallisa, Roberto Foa, Alberto Bosi, Angelo Vacca, Francesco Lanza, Giulia Palazzo, Giuseppe Avvisati, Felicetto Ferrara, Ugo Consoli, Maria Cantonetti, Emanuele Angelucci, Catello Califano, Francesco Di Raimondo, Attilio Guarini, Maurizio Musso, Michele Pizzuti, Nicola Giuliani, Antonio Ardizzoia, Nicola Di Renzo, Gianluca Gaidano, Alessandro Gozzetti, Vincenzo Pitini, Gabriella Farina, Riccardo Centurioni, Paolo De Fabritiis, Francesco Iuliano, Giorgio La Nasa, Giacinto La Verde, Fabrizio Pane, Umberto Recine, Maria La Targia, Giuseppe Mineo, Clotilde Cangialosi, Daniele Fagnani, Augusto Federici, Atelda Romano, Giorgina Specchia, Sergio Storti, Velia Bongarzoni, Andrea Bacigalupo, Marco Gobbi, Giancarlo Latte, Donato Mannina, Silvana Capalbo, Mindaugas Jurgutis, Dariusz Woszczyk, Jadwiga Hołojda, Slawomir Gornik, Andrzej Pluta, Elzbieta Morawiec-Szymonik, Slawomira Kyrcz-Krzemien, Wojciech Homenda, Sebastian Grosicki, Kazimierz Sulek, Andrzej Lange, Janusz Kloczko, Jolanta Starzak-Gwozdz, Andrzej Hellmann, Mieczyslaw Komarnicki, Kazimierz Kuliczkowski, Carolina Viveiros, Cristina Gonçalves, Natalia Esefyeva, Julia Kochkareva, Kamil Kaplanov, Elena Volodicheva, Elena Laricheva, Valentina Dergacheva, Marina Chukavina, Natalia Volchenko, Irina Nazarova, Ludmila Anchukova, Elena Ovanesova, Taras Gritsenko, Galina Salogub, Ludmila Magomedova, Irina Kuznetsova, Svetlana Osyunikhina, Olga Serdyuk, Elena Karyagina, Valentina Ivanova, Slovenia Peter Černelč, Corlia Coetzee, Karen Gunther, Dhayanithi Moodley, Soledad Duran, Asunción Echeveste Gutiérrez, Jaime Perez De Oteyza, Francisco Javier Capote, Maria Casanova, Jesus Martin Sanchez, Eduardo Rios-Herranz, Jeronima Ibañez-Garcia, Maria Jose Herranz, Belen Hernandez, Sara Sanchez Sanchez, Fernando Escalante, Fernando Carnicero, Joan Bargay Lleonart, Mercedes Gironella, Rafael Martínez, Ana Lopez De La Guia, Luis Palomera, Rebeca Iglesias, Fernando Solano Ramos, Javier De La Serna, Pedro Garcia Sanchez, Juan Besalduch Vidal, Miguel Diaz Morfa, Turkey – Meral Beksac, Filiz Vural, Yildiz Aydin, Ali Unal, Hakan Goker, Oktay Bilgir, Birol Guvenc, Mehmet Turgut, Gulsum Gulistan Ozet, Ridvan Ali, Maryna Kyselyova, Nataliia Glushko, Renata Vybyrana, Igor Skrypnyk, Natalya Tretyak, Tetiana Kharchevska, Iryna Dyagil, Tetiana Popovs'ka, Vadim Shimanskiy, Tamila Lysa, Hanna Oliynyk, Kateryna Vilchevskaya, Iryna Kryachok, Yuriy Popovych, Natalia Romanyuk, Natalia Yushchenko, Polina Kaplan, Grygoriy Rekhtman, Halyna Pylypenko, Viktor Kozlov, Johannes Drach, Jean-Luc Harousseau, Hermann Einsele, Hartmut Goldschmidt, Thierry Facon, Mauricette Michalet, Valery G. Savchenko, Javier De la Rubia, Gordon Cook, Ulf-Henrik Mellqvist, Heinz Ludwig, Millennium Pharmaceuticals, Janssen Research and Development, Mohty, Mohamad, Terpos, Evangelo, Mateos, Maria-Victoria, Cavo, Michele, Lejniece, Sandra, Beksac, Meral, Bekadja, Mohamed Amine, Legiec, Wojciech, Dimopoulos, Meletio, Stankovic, Svetlana, Durán, Maria Soledad, De Stefano, Valerio, Corso, Alessandro, Kochkareva, Yulia, Laane, Edward, Berthou, Christian, Salwender, Han, Masliak, Zvenyslava, Pečeliūnas, Valda, Willenbacher, Wolfgang, Silva, João, Louw, Vernon, Nemet, Damir, Borbényi, Zita, Abadi, Uri, Pedersen, Robert Schou, Černelč, Peter, Potamianou, Anna, Couturier, Catherine, Feys, Caroline, Thoret-Bauchet, Florence, Boccadoro, Mario, Mohty, M., Terpos, E., Mateos, M. -V., Cavo, M., Lejniece, S., Beksac, M., Bekadja, M. A., Legiec, W., Dimopoulos, M., Stankovic, S., Duran, M. S., De Stefano, V., Corso, A., Kochkareva, Y., Laane, E., Berthou, C., Salwender, H., Masliak, Z., Peceliunas, V., Willenbacher, W., Silva, J., Louw, V., Nemet, D., Borbenyi, Z., Abadi, U., Pedersen, R. S., Cernelc, P., Potamianou, A., Couturier, C., Feys, C., Thoret-Bauchet, F., Boccadoro, M., Bekadja, M., Hamladji, R. -M., Ali, H. A., Hamdi, S., Touhami, H., Mansour, N. S., Linkesch, W., Abildgaard, N., Hein, M., Eveillard, J. R., Yamani, A. E., Moreau, P., Sanhes, L., Lepeu, G., Laribi, K., Jourdan, E., Fitoussi, O., Allangba, O., Fleury, J., Escoffre, M., Benramdane, R., Cartron, G., Dine, G., Legouffe, E., Harich, H. -D., Illmer, T., Dorfel, S., Hannig, C. V., Koenigsmann, M., Prange-Krex, G., Tamm, I., Zeller, W., Maasberg, M., Schlag, R., Klausmann, M., Uhlig, J., Alkemper, B., Schutz, S., Tessen, H. -W., Mohr, B., Schmidt, P., Heinrich, B., Hebart, H., Seipelt, G., Zoeller, T., Heits, F., Muller-Naendrup, C., Hansen, R., Repp, R., Von Weikersthal, L. F., Schmits, R., Hessling, J., Krammer-Steiner, B., Janzen, V., Schauer, M., Gruner, M. W., Kisro, J., Denzlinger, C., Freier, W., Junghanss, C., Gorner, M., Laichinger, K., Ostermann, H., Durk, H., Hess, G., Reich, G., Matsouka, P., Pouli, A., Anagnostopoulos, A., Masszi, T., Ivanyi, J., Szomor, A., Nagler, A., Magen, H., Avivi, I., Quitt, M., Palumbo, A., Za, T., Vallisa, D., Foa, R., Bosi, A., Vacca, A., Lanza, F., Palazzo, G., Avvisati, G., Ferrara, F., Consoli, U., Cantonetti, M., Angelucci, E., Califano, C., Di Raimondo, F., Guarini, A., Musso, M., Pizzuti, M., Giuliani, N., Ardizzoia, A., Di Renzo, N., Gaidano, G., Gozzetti, A., Pitini, V., Farina, G., Centurioni, R., De Fabritiis, P., Iuliano, F., La Nasa, G., La Verde, G., Pane, F., Recine, U., La Targia, M., Mineo, G., Cangialosi, C., Fagnani, D., Federici, A., Romano, A., Specchia, G., Storti, S., Bongarzoni, V., Bacigalupo, A., Gobbi, M., Latte, G., Mannina, D., Capalbo, S., Jurgutis, M., Woszczyk, D., Holojda, J., Gornik, S., Pluta, A., Morawiec-Szymonik, E., Kyrcz-Krzemien, S., Homenda, W., Grosicki, S., Sulek, K., Lange, A., Kloczko, J., Starzak-Gwozdz, J., Hellmann, A., Komarnicki, M., Kuliczkowski, K., Viveiros, C., Goncalves, C., Esefyeva, N., Kaplanov, K., Volodicheva, E., Laricheva, E., Dergacheva, V., Chukavina, M., Volchenko, N., Nazarova, I., Anchukova, L., Ovanesova, E., Salogub, G., Magomedova, L., Kuznetsova, I., Osyunikhina, S., Serdyuk, O., Karyagina, E., Ivanova, V., Cernelc, S. P., Coetzee, C., Gunther, K., Moodley, D., Duran, S., Gutierrez, A. E., De Oteyza, J. P., Capote, F. J., Casanova, M., Sanchez, J. M., Rios-Herranz, E., Ibanez-Garcia, J., Herranz, M. J., Hernandez, B., Sanchez, S. S., Escalante, F., Carnicero, F., Lleonart, J. B., Gironella, M., Martinez, R., De La Guia, A. L., Palomera, L., Iglesias, R., Ramos, F. S., De La Serna, J., Sanchez, P. G., Vidal, J. B., Morfa, M. D., Beksac, T. -M., Vural, F., Aydin, Y., Unal, A., Goker, H., Bilgir, O., Guvenc, B., Turgut, M., Ozet, G. G., Ali, R., Kyselyova, M., Glushko, N., Vybyrana, R., Skrypnyk, I., Tretyak, N., Kharchevska, T., Dyagil, I., Popovs'Ka, T., Shimanskiy, V., Lysa, T., Oliynyk, H., Vilchevskaya, K., Kryachok, I., Popovych, Y., Romanyuk, N., Yushchenko, N., Kaplan, P., Rekhtman, G., Pylypenko, H., Kozlov, V., Drach, J., Harousseau, J. -L., Einsele, H., Goldschmidt, H., Facon, T., Michalet, M., Savchenko, V. G., De la Rubia, J., Cook, G., Mellqvist, U. -H., Ludwig, H., Service d'hématologie clinique et de thérapie cellulaire [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Department of Clinical Therapeutics, Univesrity of Athens, Universidad de Salamanca- CSIC, The Institute of Hematology and Oncology L. and A. Seràgnoli, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Riga Stradins University (RSU), Ankara University, University of Oran Es-Senia [Oran] | Université d'Oran Es-Senia [Oran], Medical University of Lublin, Department of Clinical Therapeutics [Athens, Greece], National and Kapodistrian University of Athens (NKUA), University Clinic of Hematology, Skopje, Complejo Hospitalario de Jaén, Institute of Hematology, Catholic University, Division of Hematology, Foundation IRCCS Policlinico San Matteo, Università degli Studi di Pavia, State Budget Healthcare Insititution of Moscow, North Estonia Medical Centre, Service d'hématologie, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Asklepios Klinik Altona, Institute of Blood Pathology and Transfusion Medicine, Lviv, Vilnius University Hospital Santariskiu Clinics, Universitätsklinik Innsbruck Innere Medizin V (Innsbruck Austria & Oncotyrol), Instituto de Engenharia de Sistemas e Computadores Investigação e Desenvolvimento em Lisboa (INESC-ID), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST)-Instituto de Engenharia de Sistemas e Computadores (INESC), University Health Network, University of the Free State [South Africa], Clinical Hospital Centre Zagreb, Szegedi Tudományegyetem, Meir Medical Center, Regionshospitalet i Holstebro, Medicinsk Afdeling, University Medical Centre Ljubljana [Ljubljana, Slovenia] (UMCL), Janssen-Cilag, Neuss, Janssen-Cilag [Issy-les-Moulineaux], Janssen Research & Development, Divisione di Ematologia dell' Università di Torino, and Azienda Ospedaliera S. Giovanni Battista di Torino
- Subjects
Male ,Cancer Research ,Boronic Acid ,[SDV]Life Sciences [q-bio] ,bortezomib ,global ,observational study ,routine practice ,stem cell transplantation ,Salvage therapy ,Practice Patterns ,Dexamethasone ,Bortezomib ,Routine practice ,0302 clinical medicine ,Global ,Observational study ,Stem cell transplantation ,hemic and lymphatic diseases ,Antineoplastic Combined Chemotherapy Protocols ,80 and over ,Prospective Studies ,Practice Patterns, Physicians' ,Prospective cohort study ,Lenalidomide ,ComputingMilieux_MISCELLANEOUS ,Multiple myeloma ,Aged, 80 and over ,Hematology ,Middle Aged ,Boronic Acids ,3. Good health ,Thalidomide ,Survival Rate ,Treatment Outcome ,Local ,Oncology ,030220 oncology & carcinogenesis ,Female ,Multiple Myeloma ,Adult ,Aged ,Follow-Up Studies ,Humans ,Neoplasm Recurrence, Local ,Salvage Therapy ,medicine.drug ,Human ,medicine.medical_specialty ,NO ,Follow-Up Studie ,03 medical and health sciences ,Internal medicine ,medicine ,Survival rate ,Physicians' ,Antineoplastic Combined Chemotherapy Protocol ,business.industry ,Settore MED/15 ,medicine.disease ,Transplantation ,Settore MED/15 - MALATTIE DEL SANGUE ,Prospective Studie ,Neoplasm Recurrence ,business ,030215 immunology - Abstract
© 2018 The Authors., [Background]: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. [Patients and Methods]: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months., [Results]: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide., [Conclusion]: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits., Writing support during the development of our report was provided by Laura Mulcahy and Catherine Crookes of FireKite, an Ashfield company, a part of UDG Healthcare plc, which was funded by Millennium Pharmaceuticals, Inc, and Janssen Global Services, LLC. The EMMOS study was supported by research funding from Janssen Pharmaceutical NV and Millennium Pharmaceuticals, Inc.
- Published
- 2018
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