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Your search keyword '"Dimopoulos, M. A."' showing total 27 results
Start Over Author "Dimopoulos, M. A." Topic bortezomib Publication Year Range Last 50 years
27 results on '"Dimopoulos, M. A."'

1. Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.

Author

Kastritis E, Gavriatopoulou M, Roussou M, Fotiou D, Ziogas DC, Migkou M, Eleutherakis-Papaiakovou E, Panagiotidis I, Kanellias N, Psimenou E, Papadopoulou E, Pamboucas C, Manios E, Gakiopoulou H, Ntalianis A, Tasidou A, Giannouli S, Terpos E, and Dimopoulos MA

Subjects
Aged, Amyloidosis pathology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bortezomib pharmacology, Cyclophosphamide pharmacology, Dexamethasone pharmacology, Female, Humans, Male, Middle Aged, Treatment Outcome, Amyloidosis drug therapy, Bortezomib therapeutic use, Cyclophosphamide therapeutic use, Dexamethasone therapeutic use
Abstract

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Published
2017
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2. Impact of prior treatment on patients with relapsed multiple myeloma treated with carfilzomib and dexamethasone vs bortezomib and dexamethasone in the phase 3 ENDEAVOR study.

Author

Moreau P, Joshua D, Chng WJ, Palumbo A, Goldschmidt H, Hájek R, Facon T, Ludwig H, Pour L, Niesvizky R, Oriol A, Rosiñol L, Suvorov A, Gaidano G, Pika T, Weisel K, Goranova-Marinova V, Gillenwater HH, Mohamed N, Aggarwal S, Feng S, and Dimopoulos MA

Subjects
Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bortezomib therapeutic use, Dexamethasone therapeutic use, Disease-Free Survival, Humans, Middle Aged, Multiple Myeloma mortality, Oligopeptides therapeutic use, Recurrence, Salvage Therapy mortality, Treatment Outcome, Bortezomib administration & dosage, Dexamethasone administration & dosage, Multiple Myeloma drug therapy, Oligopeptides administration & dosage, Salvage Therapy methods
Abstract

The randomized phase 3 ENDEAVOR study (N=929) compared carfilzomib and dexamethasone (Kd) with bortezomib and dexamethasone (Vd) in relapsed multiple myeloma (RMM). We performed a subgroup analysis from ENDEAVOR in patients categorized by number of prior lines of therapy or by prior treatment. Median progression-free survival (PFS) for patients with one prior line was 22.2 months for Kd vs 10.1 months for Vd, and median PFS for patients with ⩾2 prior lines was 14.9 months for Kd vs 8.4 months for Vd. For patients with prior bortezomib exposure, the median PFS was 15.6 months for Kd vs 8.1 months for Vd, and for patients with prior lenalidomide exposure the median PFS was 12.9 months for Kd vs 7.3 months for Vd. Overall response rates (Kd vs Vd) were 81.9 vs 65.5% (one prior line), 72.0 vs 59.7% (⩾2 prior lines), 71.2 vs 60.3% (prior bortezomib) and 70.1 vs 59.3% (prior lenalidomide). The safety profile in the prior lines subgroups was qualitatively similar to that in the broader ENDEAVOR population. In RMM, outcomes are improved when receiving treatment with carfilzomib compared with bortezomib, regardless of the number of prior therapy lines or prior exposure to bortezomib or lenalidomide.

Published
2017
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3. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis

Author

Kastritis E., Palladini G., Minnema M. C., Wechalekar A. D., Jaccard A., Lee H. C., Sanchorawala V., Gibbs S., Mollee P., Venner C. P., Lu J., Schonland S., Gatt M. E., Suzuki K., Kim K., Cibeira M. T., Beksac M., Libby E., Valent J., Hungria V., Wong S. W., Rosenzweig M., Bumma N., Huart A., Dimopoulos M. A., Bhutani D., Waxman A. J., Goodman S. A., Zonder J. A., Lam S., Song K., Hansen T., Manier S., Roeloffzen W., Jamroziak K., Kwok F., Shimazaki C., Kim J. -S., Crusoe E., Ahmadi T., Tran N., Qin X., Vasey S. Y., Tromp B., Schecter J. M., Weiss B. M., Zhuang S. H., Vermeulen J., Merlini G., Comenzo R. L., Bradley Augustson, Fiona Kwok, Peter Mollee, Simon Gibbs, Chantal Doyen, Greet Bries, Isabelle Vande Broek, Ka Lung Wu, Koen Theunissen, Koen Van Eygen, Michel Delforge, Nathalie Meuleman, Philip Vlummens, Angelo Maiolino, Breno Moreno de Gusmão, Carlos Eduardo Miguel, Edvan Crusoe, Fernanda Moura, Fernanda Seguro, Jandey Bigonha, Juliane Musacchio, Karla Zanella, Laura Garcia, Marcelo Eduardo Zanella Capra, Reijane Alves de Assis, Rosane Bittencourt, Vania Hungria, Walter Braga, Wolney Barreto, Christopher Venner, Donna Reece, Emilie Lemieux-Blanchard, Kevin Song, Michael Sebag, Selay Lam, Victor Zepeda, Haitao Zhang, Jianda Hu, Jin Lu, Juan Li, Songfu Jiang, Ting Niu, Wenming Chen, Xiaonong Chen, Zhen Cai, Zhou Fude, Maja Oelholm Vase, Morten Salomo, Niels Abildgaard, Alain Fuzibet, Anne-Marie Stoppa, Arnaud Jaccard, Bertrand Arnulf, Bruno Moulin, Bruno Royer, David Ghez, Denis Caillot, Dominique Chauveau, Franck Bridoux, Lauriane Clement-Filliatre, Lionel Karlin, Lotfi Benboubker, Mamoun Dib, Margaret Macro, Mohamad Mohty, Olivier Decaux, Olivier Hermine, Olivier Tournilhac, Philippe Moreau, Salomon Manier, Sylvain Choquet, Véronique Dorvaux, Alexander Carpinteiro, Axel Nogai, Britta Besemer, Christoph Roellig, Roland Fenk, Stefan Knop, Stefan Schönland, Timon Hansen, Argiris Symeonidis, Efstathios Kastritis, Gabor Mikala, Tamás Masszi, Zsolt Nagy, Celia Suriu, Hila Magen, Iuliana Vaxman, Lev Shvidel, Meir Preis, Moshe Gatt, Noa Lavi, Osnat Jarchowsky, Tamar Tadmor, Yael Cohen, Angelo Vacca, Giovanni Palladini, Mario Boccadoro, Maurizio Martelli, Maurizio Musso, Michele Cavo, Chihiro Shimazaki, Hiroyuki Takamatsu, Kazutaka Sunami, Kenshi Suzuki, Nagaaki Katoh, Shinsuke Iida, Takayuki Ikezoe, Tomoaki Fujisaki, Yuta Katayama, Chang Ki Min, Ho-Jin Shin, Jin Seok Kim, Jung Yong Hong, Ki Hyun Kim, Sung-Soo Yoon, Aline Ramirez, Alvaro Cabrera, Christian Ramos, David Gomez Almaguer, Deborah Martinez, Guillermo Ruiz, Helen Dayani Caballero, Juan Antonio Flores Jimenez, Annemiek Broijl, Laurens Nieuwenhuizen, Monique Minnema, Paula Ypma, Wilfried Roeloffzen, Dominik Dytfeld, Grzegorz Charlinski, Grzegorz Helbig, Krzysztof Jamroziak, Sebastian Grosicki, Wieslaw Jedrzejczak, Albert Oriol Rocafiguera, Elham Askari, Fernando Escalante Barrigon, Isabel Krsnik Castello, Javier De la Rubia Comos, Jesus Martin Sanchez, Joaquin Martinez Lopez, Jose Angel Hernandez Rivas, Luis Felipe Casado Montero, Maria Jesus Blanchard Rodriguez, Maria Teresa Cibeira Lopez, Maria Victoria Mateos Manteca, Marta Sonia Gonzalez Perez, Mercedes Gironella Mesa, Rafael Rios Tamayo, Ramon Lecumberri Villamediana, Ricarda Garcia Sanchez, Sunil Lakhwani, Yolanda Gonzalez, Hareth Nahi, Kristina Carlsson, Markus Hansson, Ulf-Henrik Mellqvist, Ali Unal, Burhan Ferhanoglu, Hayri Ozsan, Levent Undar, Mehmet Turgut, Mehmet Yilmaz, Meral Beksac, Muhlis Cem Ar, Muzaffer Demir, Sevgi Besisik, Ashutosh Wechalekar, Jamie Cavenagh, Jim Cavet, Mark Cook, Rachel Hall, Adam Waxman, Anuj Mahindra, Cesar Rodriguez Valdes, Christine Ye, Craig Reeder, Daphne Friedman, David Siegel, Divaya Bhutani, Edward Libby, Eva Medvedova, Frank Passero, Giada Bianchi, Giampaolo Talamo, Guido Tricot, Hans Lee, Heather Landau, Jan Moreb, Jason Valent, Jeffrey Matous, Jeffrey A Zonder, Jesus Berdeja, Jonathan Kaufman, Keith Stockerl-Goldstein, Keren Osman, Ketan Doshi, Kevin Barton, Larry Anderson, Manisha Bhutani, Mehmet Kocoglu, Michael Rosenzweig, Michael Schuster, Michaela Liedtke, Morie Gertz, Naresh Bumma, Natalie Callander, Raymond Comenzo, Robert Vescio, Roger Pearse, Sandy W Wong, Stacey A Goodman, Stefano Tarantolo, Taimur Sher, Tibor Kovacsovics, Tomer Mark, Vaishali Sanchorawala, William Bensinger, Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias (CHELTER), Université Clermont Auvergne (UCA), Kastritis E., Palladini G., Minnema M.C., Wechalekar A.D., Jaccard A., Lee H.C., Sanchorawala V., Gibbs S., Mollee P., Venner C.P., Lu J., Schonland S., Gatt M.E., Suzuki K., Kim K., Cibeira M.T., Beksac M., Libby E., Valent J., Hungria V., Wong S.W., Rosenzweig M., Bumma N., Huart A., Dimopoulos M.A., Bhutani D., Waxman A.J., Goodman S.A., Zonder J.A., Lam S., Song K., Hansen T., Manier S., Roeloffzen W., Jamroziak K., Kwok F., Shimazaki C., Kim J.-S., Crusoe E., Ahmadi T., Tran N., Qin X., Vasey S.Y., Tromp B., Schecter J.M., Weiss B.M., Zhuang S.H., Vermeulen J., Merlini G., and Comenzo R.L., Bradley Augustson, Fiona Kwok, Peter Mollee, Simon Gibbs, Chantal Doyen, Greet Bries, Isabelle Vande Broek, Ka Lung Wu, Koen Theunissen, Koen Van Eygen, Michel Delforge, Nathalie Meuleman, Philip Vlummens, Angelo Maiolino, Breno Moreno de Gusmão, Carlos Eduardo Miguel, Edvan Crusoe, Fernanda Moura, Fernanda Seguro, Jandey Bigonha, Juliane Musacchio, Karla Zanella, Laura Garcia, Marcelo Eduardo Zanella Capra, Reijane Alves de Assis, Rosane Bittencourt, Vania Hungria, Walter Braga, Wolney Barreto, Christopher Venner, Donna Reece, Emilie Lemieux-Blanchard, Kevin Song, Michael Sebag, Selay Lam, Victor Zepeda, Haitao Zhang, Jianda Hu, Jin Lu, Juan Li, Songfu Jiang, Ting Niu, Wenming Chen, Xiaonong Chen, Zhen Cai, Zhou Fude, Maja Oelholm Vase, Morten Salomo, Niels Abildgaard, Alain Fuzibet, Anne-Marie Stoppa, Arnaud Jaccard, Bertrand Arnulf, Bruno Moulin, Bruno Royer, David Ghez, Denis Caillot, Dominique Chauveau, Franck Bridoux, Lauriane Clement-Filliatre, Lionel Karlin, Lotfi Benboubker, Mamoun Dib, Margaret Macro, Mohamad Mohty, Olivier Decaux, Olivier Hermine, Olivier Tournilhac, Philippe Moreau, Salomon Manier, Sylvain Choquet, Véronique Dorvaux, Alexander Carpinteiro, Axel Nogai, Britta Besemer, Christoph Roellig, Roland Fenk, Stefan Knop, Stefan Schönland, Timon Hansen, Argiris Symeonidis, Efstathios Kastritis, Gabor Mikala, Tamás Masszi, Zsolt Nagy, Celia Suriu, Hila Magen, Iuliana Vaxman, Lev Shvidel, Meir Preis, Moshe Gatt, Noa Lavi, Osnat Jarchowsky, Tamar Tadmor, Yael Cohen, Angelo Vacca, Giovanni Palladini, Mario Boccadoro, Maurizio Martelli, Maurizio Musso, Michele Cavo, Chihiro Shimazaki, Hiroyuki Takamatsu, Kazutaka Sunami, Kenshi Suzuki, Nagaaki Katoh, Shinsuke Iida, Takayuki Ikezoe, Tomoaki Fujisaki, Yuta Katayama, Chang Ki Min, Ho-Jin Shin, Jin Seok Kim, Jung Yong Hong, Ki Hyun Kim, Sung-Soo Yoon, Aline Ramirez, Alvaro Cabrera, Christian Ramos, David Gomez Almaguer, Deborah Martinez, Guillermo Ruiz, Helen Dayani Caballero, Juan Antonio Flores Jimenez, Annemiek Broijl, Laurens Nieuwenhuizen, Monique Minnema, Paula Ypma, Wilfried Roeloffzen, Dominik Dytfeld, Grzegorz Charlinski, Grzegorz Helbig, Krzysztof Jamroziak, Sebastian Grosicki, Wieslaw Jedrzejczak, Albert Oriol Rocafiguera, Elham Askari, Fernando Escalante Barrigon, Isabel Krsnik Castello, Javier De la Rubia Comos, Jesus Martin Sanchez, Joaquin Martinez Lopez, Jose Angel Hernandez Rivas, Luis Felipe Casado Montero, Maria Jesus Blanchard Rodriguez, Maria Teresa Cibeira Lopez, Maria Victoria Mateos Manteca, Marta Sonia Gonzalez Perez, Mercedes Gironella Mesa, Rafael Rios Tamayo, Ramon Lecumberri Villamediana, Ricarda Garcia Sanchez, Sunil Lakhwani, Yolanda Gonzalez, Hareth Nahi, Kristina Carlsson, Markus Hansson, Ulf-Henrik Mellqvist, Ali Unal, Burhan Ferhanoglu, Hayri Ozsan, Levent Undar, Mehmet Turgut, Mehmet Yilmaz, Meral Beksac, Muhlis Cem Ar, Muzaffer Demir, Sevgi Besisik, Ashutosh Wechalekar, Jamie Cavenagh, Jim Cavet, Mark Cook, Rachel Hall, Adam Waxman, Anuj Mahindra, Cesar Rodriguez Valdes, Christine Ye, Craig Reeder, Daphne Friedman, David Siegel, Divaya Bhutani, Edward Libby, Eva Medvedova, Frank Passero, Giada Bianchi, Giampaolo Talamo, Guido Tricot, Hans Lee, Heather Landau, Jan Moreb, Jason Valent, Jeffrey Matous, Jeffrey A Zonder, Jesus Berdeja, Jonathan Kaufman, Keith Stockerl-Goldstein, Keren Osman, Ketan Doshi, Kevin Barton, Larry Anderson, Manisha Bhutani, Mehmet Kocoglu, Michael Rosenzweig, Michael Schuster, Michaela Liedtke, Morie Gertz, Naresh Bumma, Natalie Callander, Raymond Comenzo, Robert Vescio, Roger Pearse, Sandy W Wong, Stacey A Goodman, Stefano Tarantolo, Taimur Sher, Tibor Kovacsovics, Tomer Mark, Vaishali Sanchorawala, William Bensinger

Subjects
Male, Treatment outcome, Immunoglobulin Light-chain Amyloidosis/drug therapy, CD38, Dexamethasone, Cyclophosphamide/administration & dosage, Bortezomib, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Medicine, CRITERIA, Immunoglobulin Light-chain Amyloidosis, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, biology, Amyloidosis, Antibodies, Monoclonal, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, General Medicine, Middle Aged, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Female, Antibody, Human, Adult, Dexamethasone/administration & dosage, ANTIBODY DARATUMUMAB, Immunoglobulin light chain, DIAGNOSIS, Antibodies, Monoclonal/administration & dosage, Disease-Free Survival, 03 medical and health sciences, Humans, Cyclophosphamide, Aged, Antineoplastic Combined Chemotherapy Protocol, business.industry, Antineoplastic Combined Chemotherapy Protocols/adverse effects, AL AMYLOIDOSIS, Daratumumab, Amyloid fibril, medicine.disease, Molecular biology, Immunoglobulin Light-chain Amyloidosi, biology.protein, Bortezomib/administration & dosage, business, 030215 immunology
Abstract

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease.We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response.A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy.Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).

Published
2021

4. Efficacy and safety of weekly carfilzomib (70 mg/m2), dexamethasone, and daratumumab (KdD70) is comparable to twice-weekly KdD56 while being a more convenient dosing option : a cross-study comparison of the CANDOR and EQUULEUS studies

Author

Leleu, X., Beksac, M., Chou, T., Dimopoulos, M., Yoon, S.S., Prince, H.M., Pour, L., Shelekhova, T., Chari, A., Khurana, M., Zhang, J., Obreja, M., Qi, M., Oriol, Albert, Siegel, D., and Universitat Autònoma de Barcelona

Subjects
Oncology, Cancer Research, medicine.medical_specialty, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Multiple myeloma, Internal medicine, Daratumumab, medicine, Dosing, Dexamethasone, Lenalidomide, business.industry, Bortezomib, Carfilzomib, Hematology, Weekly regimen, Regimen, chemistry, 030220 oncology & carcinogenesis, Propensity score matching, business, 030215 immunology, medicine.drug
Abstract

The regimen of carfilzomib, daratumumab, and dexamethasone (KdD) shows activity in patients with relapsed/refractory multiple myeloma. KdD at the twice-weekly 56 mg/m2 carfilzomib dose (KdD56) was used in the randomized phase 3 CANDOR study (NCT03158688), whereas KdD at the once-weekly 70 mg/m2 carfilzomib dose (KdD70) was used in the phase 1 b EQUULEUS study (NCT01998971). We analyzed efficacy data from comparable CANDOR and EQUULEUS patients using inverse probability of treatment weighting (IPTW)-adjusted models. These weights were calculated from propensity scores derived to balance prespecified baseline covariates. The side-by-side and adjusted comparisons showed similar efficacy for overall response rates and progression-free survival in the two groups, with a series of sensitivity analyses showing consistent findings. Safety data were generally consistent with the known safety profiles of each individual drug. Once-weekly KdD70 is comparable to twice-weekly KdD56 in terms of efficacy and safety while being a more convenient dosing option.

Published
2021

5. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group

Author

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

Published
2013
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7. Management of treatment-emergent peripheral neuropathy in multiple myeloma

Author

Richardson, P G, Delforge, M, Beksac, M, Wen, P, Jongen, J L, Sezer, O, Terpos, E, Munshi, N, Palumbo, A, Rajkumar, S V, Harousseau, J L, Moreau, P, Avet-Loiseau, H, Lee, J H, Cavo, M, Merlini, G, Voorhees, P, Chng, W J, Mazumder, A, Usmani, S, Einsele, H, Comenzo, R, Orlowski, R, Vesole, D, Lahuerta, J J, Niesvizky, R, Siegel, D, Mateos, M-V, Dimopoulos, M, Lonial, S, Jagannath, S, Bladé, J, Miguel, J San, Morgan, G, Anderson, K C, Durie, B G M, and Sonneveld, P

Published
2012
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13. Carfilzomib-Dexamethasone Versus Bortezomib-Dexamethasone in Relapsed or Refractory Multiple Myeloma: Updated Overall Survival, Safety, and Subgroups

Author

Orlowski, R. Z., Moreau, P., Niesvizky, R., Ludwig, H., Oriol, Albert, Chng, W. J., Goldschmidt, H., Yang, Z., Kimball, A. S., Dimopoulos, M., and Universitat Autònoma de Barcelona

Subjects
Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Efficacy, Phases of clinical research, Dexamethasone, Bortezomib, 03 medical and health sciences, chemistry.chemical_compound, Phase III, 0302 clinical medicine, Clinical outcomes, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Proteasome inhibitor, Multiple myeloma, Aged, Lenalidomide, Salvage Therapy, Proportional hazards model, business.industry, Hazard ratio, Hematology, Prognosis, medicine.disease, Carfilzomib, Survival Rate, 030104 developmental biology, chemistry, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Female, Patient Safety, Neoplasm Recurrence, Local, Multiple Myeloma, business, Oligopeptides, Follow-Up Studies, medicine.drug
Abstract

In this updated analysis of patients with relapsed/refractory multiple myeloma (RRMM) from the RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma (ENDEAVOR) trial, clinically meaningful overall survival improvements continue to be observed with carfilzomib 56 mg/m(2) and dexamethasone (Kd56; n = 464) versus bortezomib and dexamethasone (n = 465), including in key patient subgroups. With longer-term data, the favorable benefit-risk profile of Kd56 continues to support its use as a standard-of-care in RRMM. Introduction: The phase III RandomizEd, OpeN Label, Phase 3 Study of Carfilzomib Plus DExamethAsone Vs Bortezomib Plus DexamethasOne in Patients With Relapsed Multiple Myeloma (ENDEAVOR) trial showed significantly improved progression-free survival and overall survival (OS) with carfilzomib (56 mg/m(2)) and dexamethasone (Kd56) versus bortezomib and Kd56 (Vd) in patients with relapsed or refractory multiple myeloma (RRMM). We report updated OS and safety data after 6 months of additional follow-up. Patients and Methods: Patients with RRMM (1-3 previous lines of therapy) were randomized 1:1 to Kd56 or Vd. Median OS was estimated using the KaplaneMeier method; OS was compared between treatment groups using Cox proportional hazards models. Results: As of July 19, 2017, median follow-up was 44.3 months for Kd56 and 43.7 months for Vd. Median OS was 47.8 months (Kd56) versus 38.8 months (Vd; hazard ratio, 0.76; 95% confidence interval, 0.633-0.915). OS was longer with Kd56 versus Vd within age and cytogenetic subgroups, and according to number of previous lines of therapy, previous bortezomib exposure, previous lenalidomide exposure, and lenalidomide-refractory status. Exposure-adjusted incidences per 100 patient-years of adverse events (AEs) were 1352.07 for Kd56 and 1754.86 for Vd; for Grade >= 3 AEs, these values were 162.31 and 175.90. Conclusion: With median follow-up of approximately 44 months, clinically meaningful improvements in OS were observed with Kd56 versus Vd, including in all subgroups examined. The Kd56 safety profile was consistent with previous analyses.

Published
2019

14. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): And randomised, phase 3, open-label, multicentre study

Author

Dimopoulos, Ma, Moreau, P, Palumbo, A, Joshua, D, Pour, L, Hájek, R, Facon, T, Ludwig, H, Oriol, A, Goldschmidt, H, Rosiñol, L, Straub, J, Suvorov, A, Araujo, C, Rimashevskaya, E, Pika, T, Gaidano, G, Weisel, K, Goranova Marinova, V, Schwarer, A, Minuk, L, Masszi, T, Karamanesht, I, Offidani, M, Hungria, V, Spencer, A, Orlowski, Rz, Gillenwater, Hh, Mohamed, N, Feng, S, Chng, Wj, ENDEAVOR Investigators: Leahy, M, Kerridge, I, Durrant, S, Cooney, J, Horvath, N, Rowlings, P, Hahn, U, Fay, K, Renwick, W, Quach, H, Taylor, K, Ho, Sj, Johnston, A, Kasparu, H, Delforge, M, Schots, H, Vekemans, Mc, Offner, F, Wu, Kl, Doyen, C, Bittencourt, R, Duarte, G, Maiolino, A, Schaan, M, Scheliga, A, Zadra, C, Gercheva, L, Mihaylov, G, Grudeva Popova, Z, Sandhu, I, Reiman, A, Kanjeekal, S, Dueck, G, Leblanc, R, Tay, J, White, D, Maisnar, V, Scudla, V, Gregora, E, Hajek, R, Stoppa, Am, Karlin, L, Garderet, L, Fermand, Jp, Lenain, P, Rigaudeau, S, Eveillard, Jr, Escoffre Barbe, M, Knop, S, Kropff, M, Rollig, C, Munder, M, Langer, C, Mugge, Lo, Hanel, M, Niederwieser, D, Dimopoulos, M, Egyed, M, Szomor, A, Borbenyi, Z, Illes, A, Yehuda, Db, Benyamini, N, Nagler, A, Mittleman, M, Izhar, H, Cavo, M, De Fabritiis, P, Petrini, Mario, Foa, R, Gobbi, M, Rossi, G, Guglielmelli, T, Lazzaro, A, Musto, P, Gozzetti, A, Takazako, N, Izumi, T, Chou, T, Ozaki, S, Hatake, K, Suzuki, K, Uike, N, Asakura, S, Kosugi, H, Handa, H, Matsumoto, M, Tobinai, K, Iida, S, Kizaki, M, Miyamoto, T, Shibayama, H, Ando, K, Ishikawa, T, Ishida, T, Sugiura, I, Izutsu, K, Taniwaki, M, Lee, Jh, Kim, K, Kim, Js, Min, Ck, Yoon, Ss, Lee, Jo, Suh, C, Simpson, D, Ganly, P, Blacklock, H, Doocey, R, Chiruka, S, Hellmann, A, Gornik, S, Komarnicki, M, Malgorzata, Calbecka, Grosicki, S, Jurczyszyn, A, Stoia, R, Gheorghita, E, Danaila, Cd, Abdulkadyrov, K, Zaritskiy, A, Andreeva, N, Balakireva, T, Podoltseva, E, Rossiev, V, Pristupa, A, Hsieh, Ws, Gopalakrishnan, Sk, Mistrik, M, Rocafiguera, Ao, Mateos, V, Rubia, J, Dachs, Lr, Sanchez, Jm, Alegre, A, Bargay, J, de Oteyza JP, Martinez, J, Chen, Ty, Lin, Tl, Liu, Jh, Wang, Mc, Yeh, Sp, Huang, Sy, Vinnyk, Y, Kriachok, I, Pylypenko, H, Shparyk, Y, Kaplan, P, Karamanesht, L, Rekhtman, G, Romanyuk, N, Kaiser, M, Mehta, A, Williams, C, Basu, S, Rabin, N, Ramasamy, K, Hunter, H, Tholouli, E, Lebovic, D, Siegel, D, Wang, M, Niesvizky, R, Kovacsovics, T, Hurd, D, Gabrail, N, Matous, J, Pendergrass, K, Agrawal, M, Boccia, R, Chandra, S, Kassim, A, Stanisic, S, Coleman, M, Gersten, T, Braunschweig, I, Chowdhury, S, Sahovic, E., Dimopoulos, Meletios A, Moreau, Philippe, Palumbo, Antonio, Joshua, Dougla, Pour, Ludek, Hájek, Roman, Facon, Thierry, Ludwig, Heinz, Oriol, Albert, Goldschmidt, Hartmut, Rosiñol, Laura, Straub, Jan, Suvorov, Aleksandr, Araujo, Carla, Rimashevskaya, Elena, Pika, Toma, Gaidano, Gianluca, Weisel, Katja, Goranova-Marinova, Vesselina, Schwarer, Anthony, Minuk, Leonard, Masszi, Tamá, Karamanesht, Ievgenii, Offidani, Massimo, Hungria, Vania, Spencer, Andrew, Orlowski, Robert Z, Gillenwater, Heidi H, Mohamed, Nehal, Feng, Shibao, Chng, Wee-Joo, Cavo, M, Laboratory of Molecullar and Cellular Therapy, and Clinical sciences

Subjects
Oncology, Male, Clinical Trial, Phase III, Dexamethasone, Ixazomib, Bortezomib, chemistry.chemical_compound, 0302 clinical medicine, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Elotuzumab, Multiple myeloma, education.field_of_study, Research Support, Non-U.S. Gov't, Medicine (all), Anemia, Multicenter Study, Survival Rate, 030220 oncology & carcinogenesis, Randomized Controlled Trial, Hypertension, Retreatment, Oligopeptide, Female, Multiple Myeloma, Oligopeptides, Human, medicine.drug, medicine.medical_specialty, Aged, Disease-Free Survival, Follow-Up Studies, Humans, Pneumonia, Thrombocytopenia, Population, Follow-Up Studie, 03 medical and health sciences, Internal medicine, medicine, Comparative Study, education, Antineoplastic Combined Chemotherapy Protocol, business.industry, medicine.disease, Carfilzomib, Surgery, chemistry, Proteasome inhibitor, business, 030215 immunology
Abstract

BACKGROUND: Bortezomib with dexamethasone is a standard treatment option for relapsed or refractory multiple myeloma. Carfilzomib with dexamethasone has shown promising activity in patients in this disease setting. The aim of this study was to compare the combination of carfilzomib and dexamethasone with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. METHODS: In this randomised, phase 3, open-label, multicentre study, patients with relapsed or refractory multiple myeloma who had one to three previous treatments were randomly assigned (1:1) using a blocked randomisation scheme (block size of four) to receive carfilzomib with dexamethasone (carfilzomib group) or bortezomib with dexamethasone (bortezomib group). Randomisation was stratified by previous proteasome inhibitor therapy, previous lines of treatment, International Staging System stage, and planned route of bortezomib administration if randomly assigned to bortezomib with dexamethasone. Patients received treatment until progression with carfilzomib (20 mg/m(2) on days 1 and 2 of cycle 1; 56 mg/m(2) thereafter; 30 min intravenous infusion) and dexamethasone (20 mg oral or intravenous infusion) or bortezomib (1·3 mg/m(2); intravenous bolus or subcutaneous injection) and dexamethasone (20 mg oral or intravenous infusion). The primary endpoint was progression-free survival in the intention-to-treat population. All participants who received at least one dose of study drug were included in the safety analyses. The study is ongoing but not enrolling participants; results for the interim analysis of the primary endpoint are presented. The trial is registered at ClinicalTrials.gov, number NCT01568866. FINDINGS: Between June 20, 2012, and June 30, 2014, 929 patients were randomly assigned (464 to the carfilzomib group; 465 to the bortezomib group). Median follow-up was 11·9 months (IQR 9·3-16·1) in the carfilzomib group and 11·1 months (8·2-14·3) in the bortezomib group. Median progression-free survival was 18·7 months (95% CI 15·6-not estimable) in the carfilzomib group versus 9·4 months (8·4-10·4) in the bortezomib group at a preplanned interim analysis (hazard ratio [HR] 0·53 [95% CI 0·44-0·65]; p

Published
2016

15. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib:A multicenter international myeloma working group study

Author

Kumar S. K., Lee J. H., Lahuerta J. J., Morgan G., Richardson P. G., Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X., Hulin C., Klein S. K., Sonneveld P., Siegel D., Bladé J., Goldschmidt H., Jagannath S., Miguel J. S., Orlowski R., Palumbo A., Sezer O., Rajkumar S. V., Durie B. G. International Myeloma Working Group Abildgaard N, Abonour R, Alexanian R, Alsina M, Anderson KC, Attal M, Avet Loiseau H, Badros A, Baris D, Barlogie B, Bataille R, Beksaç M, Belch A, Ben Yehuda D, Bensinger B, Bergsagel PL, Bird J, Bladé J, Boccadoro M, Chanan Khan A, Chen WM, Child T, Chim J, Chng WJ, Comenzo R, Crowley J, Dalton W, Davies F, de Souza C, Delforge M, Dimopoulos M, Dispenzieri A, Drach J, Drake M, Durie BG, Einsele H, Facon T, Fantl D, Fermand JP, Fonseca R, Gahrton G, García Sanz R, Gasparetto C, Gertz M, Gibson J, Giralt S, Goldschmidt H, Greipp P, Hajek R, Hardan I, Hari P, Harousseau JL, Hata H, Hattori Y, Heffner T, Ho J, Hungria V, Ida S, Jacobs P, Jagannath S, Johnsen HE, Jian H, Joshua D, Jurczyszyn A, Kawano M, Kröger N, Kumar S, Kyle RA, Lacy M, Lahuerta JJ, Landgren O, Laubach J, Lee JH, LeLeu X, Lentzsch S, Lokhorst H, Lonial S, Ludwig H, Maiolino A, Mateos M, Mehta J, Mellqvist UH, Merlini G, Mikhael J, Morales AR, Moreau P, Morgan G, Nahi H, Munshi N, Niesvizky R, Nouel A, Novis Y, Orlowski R, Palumbo A, Pavlovsky S, Pilarski L, Powles R, Raje N, Rajkumar SV, Reece D, Reiman T, Richardson PG, Roodman D, Rosiñol L, San Miguel J, Sezer O, Shah JJ, Shaughnessy J, Shimizu K, Shustik C, Siegel D, Singhal S, Sonneveld P, Spencer A, Stadtmauer E, Stewart K, Terpos E, Tosi P, Tricot G, Turesson I, Van Camp B, Van Ness B, Van Riet I, Vande Broek I, Vanderkerken K, Vescio R, Vesole D, Waage A, Wang M, Weber D, Westin J, Wheatley K, Zonder J., CAVO, MICHELE, Kumar S.K., Lee J.H., Lahuerta J.J., Morgan G., Richardson P.G., Crowley J., Haessler J., Feather J., Hoering A., Moreau P., LeLeu X., Hulin C., Klein S.K., Sonneveld P., Siegel D., Bladé J., Goldschmidt H., Jagannath S., Miguel J.S., Orlowski R., Palumbo A., Sezer O., Rajkumar S.V., Durie B.G. International Myeloma Working Group Abildgaard N, Abonour R, Alexanian R, Alsina M, Anderson KC, Attal M, Avet-Loiseau H, Badros A, Baris D, Barlogie B, Bataille R, Beksaç M, Belch A, Ben-Yehuda D, Bensinger B, Bergsagel PL, Bird J, Bladé J, Boccadoro M, Cavo M, Chanan-Khan A, Chen WM, Child T, Chim J, Chng WJ, Comenzo R, Crowley J, Dalton W, Davies F, de Souza C, Delforge M, Dimopoulos M, Dispenzieri A, Drach J, Drake M, Durie BG, Einsele H, Facon T, Fantl D, Fermand JP, Fonseca R, Gahrton G, García-Sanz R, Gasparetto C, Gertz M, Gibson J, Giralt S, Goldschmidt H, Greipp P, Hajek R, Hardan I, Hari P, Harousseau JL, Hata H, Hattori Y, Heffner T, Ho J, Hungria V, Ida S, Jacobs P, Jagannath S, Johnsen HE, Jian H, Joshua D, Jurczyszyn A, Kawano M, Kröger N, Kumar S, Kyle RA, Lacy M, Lahuerta JJ, Landgren O, Laubach J, Lee JH, LeLeu X, Lentzsch S, Lokhorst H, Lonial S, Ludwig H, Maiolino A, Mateos M, Mehta J, Mellqvist UH, Merlini G, Mikhael J, Morales AR, Moreau P, Morgan G, Nahi H, Munshi N, Niesvizky R, Nouel A, Novis Y, Orlowski R, Palumbo A, Pavlovsky S, Pilarski L, Powles R, Raje N, Rajkumar SV, Reece D, Reiman T, Richardson PG, Roodman D, Rosiñol L, San Miguel J, Sezer O, Shah JJ, Shaughnessy J, Shimizu K, Shustik C, Siegel D, Singhal S, Sonneveld P, Spencer A, Stadtmauer E, Stewart K, Terpos E, Tosi P, Tricot G, Turesson I, Van Camp B, Van Ness B, Van Riet I, Vande Broek I, Vanderkerken K, Vescio R, Vesole D, Waage A, Wang M, Weber D, Westin J, Wheatley K, Zonder J., and Hematology

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, NATURAL HISTORY, Antineoplastic Agents, Context (language use), RELAPSE, Article, Recurrence, Internal medicine, medicine, Humans, Immunologic Factors, Elotuzumab, Survival analysis, Multiple myeloma, Aged, Aged, 80 and over, Isatuximab, Bortezomib, business.industry, Hematology, Middle Aged, Pomalidomide, medicine.disease, Survival Analysis, Surgery, Regimen, SURVIVAL, Disease Progression, Female, Multiple Myeloma, business, medicine.drug
Abstract

Promising new drugs are being evaluated for treatment of multiple myeloma (MM), but their impact should be measured against the expected outcome in patients failing current therapies. However, the natural history of relapsed disease in the current era remains unclear. We studied 286 patients with relapsed MM, who were refractory to bortezomib and were relapsed following, refractory to or ineligible to receive, an IMiD (immunomodulatory drug), had measurable disease, and ECOG PS of 0, 1 or 2. The date patients satisfied the entry criteria was defined as time zero (T-0). The median age at diagnosis was 58 years, and time from diagnosis to T-0 was 3.3 years. Following T-0, 213 (74%) patients had a treatment recorded with one or more regimens (median = 1; range 0-8). The first regimen contained bortezomib in 55 (26%) patients and an IMiD in 70 (33%). A minor response or better was seen to at least one therapy after T0 in 94 patients (44%) including >= partial response in 69 (32%). The median overall survival and event-free survival from T-0 were 9 and 5 months, respectively. This study confirms the poor outcome, once patients become refractory to current treatments. The results provide context for interpreting ongoing trials of new drugs. Leukemia (2012) 26, 149-157; doi:10.1038/leu.2011.196; published online 29 July 2011

Published
2012

16. Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma.

Author

Dimopoulos, M A, Leleu, X, Palumbo, A, Moreau, P, Delforge, M, Cavo, M, Ludwig, H, Morgan, G J, Davies, F E, Sonneveld, P, Schey, S A, Zweegman, S, Hansson, M, Weisel, K, Mateos, M V, Facon, T, and Miguel, J F S

Subjects
*MULTIPLE myeloma treatment, *DISEASE relapse, *DEXAMETHASONE, *BORTEZOMIB, *DISEASE progression, *NEUTROPENIA, *THERAPEUTICS
Abstract

In this report, a panel of European myeloma experts discuss the role of pomalidomide in the treatment of relapsed and refractory multiple myeloma (RRMM). Based on the available evidence, the combination of pomalidomide and low-dose dexamethasone is a well-tolerated and effective treatment option for patients with RRMM who have exhausted treatment with lenalidomide and bortezomib. The optimal starting dose of pomalidomide is 4 mg given on days 1-21 of each 28-day cycle, whereas dexamethasone is administered at a dose of 40 mg weekly (reduced to 20 mg for patients aged >75 years). The treatment should continue until evidence of disease progression or unacceptable toxicity. Dose-modification schemes have been established for patients who develop neutropenia, thrombocytopaenia and other grade 3-4 adverse events during pomalidomide therapy. Guidance on the prevention and management of infections and venous thromboembolism is provided, based on the available clinical evidence and the experience of panel members. The use of pomalidomide in special populations, such as patients with advanced age, renal impairment or unfavourable cytogenetic features, is also discussed. [ABSTRACT FROM AUTHOR]

Published
2014
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17. VTD consolidation, without bisphosphonates, reduces bone resorption and is associated with a very low incidence of skeletal-related events in myeloma patients post ASCT.

Author

Terpos, E, Christoulas, D, Kastritis, E, Roussou, M, Migkou, M, Eleutherakis-Papaiakovou, E, Gavriatopoulou, M, Gkotzamanidou, M, Kanellias, N, Manios, E, Papadimitriou, C, and Dimopoulos, M A

Subjects
DIPHOSPHONATES, BONE resorption, STEM cell transplantation, BORTEZOMIB, THALIDOMIDE, DEXAMETHASONE
Abstract

We prospectively evaluated the effect of bortezomib, thalidomide and dexamethasone (VTD) consolidation on bone metabolism of 42 myeloma patients who underwent an autologous stem cell transplantation (ASCT). VTD started on day 100 post ASCT; patients received four cycles of VTD (first block), were followed without treatment for 100 days and then received another four VTD cycles (second block). During this 12-month period, bisphosphonates were not administered. Best response included stringent complete remission (sCR) in 15 (35.7%) patients, complete response (CR) in 13 (30.9%), vgPR in 7 (16.6%), PR in 4 (9.5%), while 3 (7.1%) patients developed a progressive disease (PD). Importantly, 33.3% and 47.6% of patients improved their status of response after the first and second VTD block, respectively. VTD consolidation resulted in a significant reduction of circulating C-terminal cross-linking telopeptide of collagen type I (CTX), soluble receptor activator of the nuclear factor-kappa B ligand (sRANKL) and osteocalcin (OC), whereas bone-specific alkaline phosphatase (bALP) remained stable compared with pre-VTD values. During the study period, only one patient with a PD developed a skeletal-related event (that is, radiation to bone). The median time to progression (TTP) after ASCT was 34 months and the median time of next treatment was 40 months. We conclude that VTD consolidation post ASCT reduces bone resorption and is associated with a very low incidence of skeletal-related events (SREs) despite the absence of bisphosphonates; the later do not appear to be necessary in this context. [ABSTRACT FROM AUTHOR]

Published
2014
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18. Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents.

Author

Dimopoulos, M. A., Delimpasi, S., Katodritou, E., Vassou, A., Kyrtsonis, M. C., Repousis, P., Kartasis, Z., Parcharidou, A., Michael, M., Michalis, E., Gika, D., Symeonidis, A., Pouli, A., Konstantopoulos, K., Terpos, E., and Kastritis, E.

Subjects
*MULTIPLE myeloma treatment, *KIDNEY failure, *DISEASE incidence, *OLDER patients, *BORTEZOMIB, *THALIDOMIDE, *HEALTH outcome assessment
Abstract

The incidence and severity of renal impairment at the time of diagnosis of myeloma remains unchanged during the past 20 years due to increasing numbers of elderly patients who are diagnosed and treated for myeloma. Novel therapies have improved significantly the survival of patients with severe renal dysfunction and may also decrease the risk of early death which is high in patients with severe renal impairment, especially among older patients.Background Renal impairment (RI) is a common presenting complication of multiple myeloma (MM); the availability of new treatments has improved the outcomes of patients with MM; however, their impact on the survival of patients who present with RI has not been extensively studied. Patients and methods We analyzed the characteristics and outcomes of 1773 consecutive unselected patients who were treated for symptomatic myeloma since January 1990. Results Although there was a significant increase in the proportion of patients of advanced age in the more recent periods, the frequency of RI as well as the proportion of patients who presented with severe RI (eGFR < 30 ml/min/1.73 m2) remained unchanged around 18%. Thus, after adjustment for age, there was a decrease in the risk of severe RI at presentation after 2000. Myeloma response rates (≥PR) to frontline therapy have substantially increased, and this was translated in a significant increase in the median survival. Specifically for patients with severe RI, the median OS has improved from 18 and 19.5 months in the 1990–1994 and 1995–1999 to 29 and 32 months for the periods 2000–2004 and after 2005 (P = 0.005). Severe RI was associated with a high risk of early death (12% versus 7% for patients with moderate RI versus 3% for patients with mild or no RI (P < 0.001), especially among older patients, and has remained unchanged over time. Conclusions There has been a major improvement in the survival of patients with severe RI in the past decade, despite the increasing numbers of patients of advanced age. However, the risk of early death remains high in patients with severe RI, especially in the elderly. [ABSTRACT FROM AUTHOR]

Published
2014
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19. Expert review on soft-tissue plasmacytomas in multiple myeloma: definition, disease assessment and treatment considerations

Author

Laura Rosiñol, Meral Beksac, Elena Zamagni, Niels W. C. J. Van de Donk, Kenneth C. Anderson, Ashraf Badros, Jo Caers, Michele Cavo, Meletios‐Athanasios Dimopoulos, Angela Dispenzieri, Hermann Einsele, Monika Engelhardt, Carlos Fernández de Larrea, Gösta Gahrton, Francesca Gay, Roman Hájek, Vania Hungria, Artur Jurczyszyn, Nicolaus Kröger, Robert A. Kyle, Fernando Leal da Costa, Xavier Leleu, Suzanne Lentzsch, Maria V. Mateos, Giampaolo Merlini, Mohamad Mohty, Philippe Moreau, Leo Rasche, Donna Reece, Orhan Sezer, Pieter Sonneveld, Saad Z. Usmani, Karin Vanderkerken, David H. Vesole, Anders Waage, Sonja Zweegman, Paul G. Richardson, Joan Bladé, Rosinol L., Beksac M., Zamagni E., Van de Donk N.W.C.J., Anderson K.C., Badros A., Caers J., Cavo M., Dimopoulos M.-A., Dispenzieri A., Einsele H., Engelhardt M., Fernandez de Larrea C., Gahrton G., Gay F., Hajek R., Hungria V., Jurczyszyn A., Kroger N., Kyle R.A., Leal da Costa F., Leleu X., Lentzsch S., Mateos M.V., Merlini G., Mohty M., Moreau P., Rasche L., Reece D., Sezer O., Sonneveld P., Usmani S.Z., Vanderkerken K., Vesole D.H., Waage A., Zweegman S., Richardson P.G., Blade J., Hematology, R&D centraal, and Basic (bio-) Medical Sciences

Subjects
Oncology, paraskeletal plasmacytomas, Dexamethasone, Bortezomib, 0302 clinical medicine, Autologous stem-cell transplantation, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, extramedullary disease, Lenalidomide, Multiple myeloma, Etoposide, education.field_of_study, treatment, Hematopoietic Stem Cell Transplantation, Disease Management, Hematology, multiple myeloma, plasmacytoma, prognosis, soft tissue, 030220 oncology & carcinogenesis, medicine.drug, Human, medicine.medical_specialty, Prognosi, Population, Transplantation, Autologous, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, paraskeletal plasmacytoma, education, Cyclophosphamide, Antineoplastic Combined Chemotherapy Protocol, business.industry, Animal, medicine.disease, Thalidomide, Regimen, Doxorubicin, Proteasome inhibitor, Plasmacytoma, Cisplatin, business, 030215 immunology
Abstract

In this review, two types of soft-tissue involvement in multiple myeloma are defined: (i) extramedullary (EMD) with haematogenous spread involving only soft tissues and (ii) paraskeletal (PS) with tumour masses arising from skeletal lesions. The incidence of EMD and PS plasmacytomas at diagnosis ranges from 1·7% to 4·5% and 7% to 34·4% respectively. EMD disease is often associated with high-risk cytogenetics, resistance to therapy and worse prognosis than in PS involvement. In patients with PS involvement a proteasome inhibitor-based regimen may be the best option followed by autologous stem cell transplantation (ASCT) in transplant eligible patients. In patients with EMD disease who are not eligible for ASCT, a proteasome inhibitor-based regimen such as lenalidomide-bortezomib-dexamethasone (RVD) may be the best option, while for those eligible for high-dose therapy a myeloma/lymphoma-like regimen such as bortezomib, thalidomide and dexamethasone (VTD)-RVD/cisplatin, doxorubicin, cyclophosphamide and etoposide (PACE) followed by SCT should be considered. In both EMD and PS disease at relapse many strategies have been tried, but this remains a high-unmet need population.

Published
2021

20. Multiple Myeloma Treatment in Real-world Clinical Practice: Results of a Prospective, Multinational, Noninterventional Study

Author

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

21. Natural history of relapsed myeloma, refractory to immunomodulatory drugs and proteasome inhibitors: a multicenter IMWG study

Author

W. J. Chng, Michele Cavo, Shaji Kumar, Chang-Ki Min, Xavier Leleu, Charalampia Kyriakou, Sundar Jagannath, M.V. Mateos, Daniel D Waller, Je-Jung Lee, Ravi Vij, Evangelos Terpos, Chaim Shustik, Jens Hillengass, Heinz Ludwig, Dominik Dytfeld, Brian G.M. Durie, Parameswaran Hari, Hareth Nahi, Meral Beksac, Laura Rosiñol, Philippe Moreau, Ashraf Badros, Jin Seok Kim, Saad Z. Usmani, Ingela Turesson, Markus Hansson, Hyeon Seok Eom, H. Goldschmidt, Albert Oriol, E Kastritis, Tomer M Mark, Meletios A. Dimopoulos, Michel Delforge, J.J. Lahuerta, Elizabeth O'Donnell, J de la Rubia, Melissa Alsina, Paula Rodriguez Otero, Je-Hwan Lee, Ki-Hyun Kim, Ulf-Henrik Mellqvist, Henk M. Lokhorst, N W C J van de Donk, Shuji Ozaki, Enrique M. Ocio, Anna Sureda, Kumar, S. K, Dimopoulos, M. A, Kastritis, E, Terpos, E, Nahi, H, Goldschmidt, H, Hillengass, J, Leleu, X, Beksac, M, Alsina, M, Oriol, A, Cavo, M, Ocio, E. M, Mateos, M. V, O'Donnell, E. K, Vij, R, Lokhorst, H. M, van de Donk, N. W. C. J, Min, C, Mark, T, Turesson, I, Hansson, M, Ludwig, H, Jagannath, S, Delforge, M, Kyriakou, C, Hari, P, Mellqvist, U, Usmani, S. Z, Dytfeld, D, Badros, A. Z, Moreau, P, Kim, K, Otero, P. R, Lee, J. H, Shustik, C, Waller, D, Chng, W. J, Ozaki, S, Lee, J-J, de la Rubia, J, Eom, H. S, Rosinol, L, Lahuerta, J. J, Sureda, A, Kim, J. S, Durie, B. G. M., Hematology, and CCA - Cancer Treatment and quality of life

Subjects
Oncology, Male, Cancer Research, Improved survival, Biochemistry, Cohort Studies, chemistry.chemical_compound, Asia pacific, 0302 clinical medicine, Recurrence, Medicine, Multiple myeloma, Aged, 80 and over, Treatment regimen, Bortezomib, Treatment options, Hematology, Middle Aged, Prognosis, Management, Proteasome Inhibitor, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, Bristol-Myers, Proteasome Inhibitors, medicine.drug, Human, Adult, medicine.medical_specialty, Prognosi, Immunology, 03 medical and health sciences, Refractory, Adjuvants, Immunologic, Internal medicine, Overall survival, Humans, In patient, Survival analysis, Lenalidomide, Aged, business.industry, Cell Biology, medicine.disease, Pomalidomide, Carfilzomib, Survival Analysis, Surgery, Board (committee), Regimen, chemistry, Cohort Studie, business, 030215 immunology
Abstract

Background: Treatment of multiple myeloma has evolved considerably in the past few years with availability of several news drugs as well as increasing use of multidrug combinations. These changes have no doubt led to the improved survival seen among patients with MM. We have previously shown that outcomes of patients intolerant or refractory to one of the IMiDs and bortezomib had a poor outcome. Since that time, other drugs of the same class as well as new classes of drugs have been introduced for the treatment of MM. We designed this retrospective study to estimate the outcomes in patients with relapsed myeloma, who have become refractory to the current generation IMiDs and proteasome inhibitors. Patients and Methods: Patients with relapsed multiple myeloma who have received at least 3 prior lines of therapy, is refractory to both an IMiD (lenalidomide or pomalidomide) AND a proteasome inhibitor (bortezomib or carfilzomib), and has been exposed to an alkylating agent were identified from multiple centers. The time patients met the above criteria was defined as T0, and details of all treatment regimens before and after T0 were collected using electronic CRFs. The study was approved by the IRB at the respective centers. Results: 543 patients were enrolled in this study; median age was 62 years (31-87) and 61% were males. Patients were enrolled from centers in North America (n=181), Europe (n=318), and Asia Pacific (n=44). Patients were diagnosed between 2006 and 2014, the median duration between diagnosis of myeloma and study entry (T0) was 3.1 years (0.3 to 9). The median (95% CI) estimated follow up from diagnosis and from T0 were 61 (57, 66) months and 13 (11, 15) months respectively. The median number of lines of therapy prior to T0 was 4 (3-13), 48% had a prior transplant. The median OS from T0 for the entire cohort was 13 (11, 15) months. For these 462 patients, the median number of recorded regimens was 2 (1-9). The overall response and the depth of response to each line of treatment following T0 are as shown in the table. The median (95% CI) PFS and OS from T0 was 5 (4, 6), and 15.2 (13, 17), respectively. The overall survival for the 81 patients with no treatment post T0 was only 2.1 months. In a multivariate analysis, duration from diagnosis to T0, ISS stage III and number of lines of therapy were all associated with inferior PFS, as well as OS, and in addition, serum creatinine>2 mg/dL at T0 also predicted inferior OS. Conclusions: The study provides the expected outcome following development of myeloma that is refractory to a PI and an IMiD. The outcomes of these patients appear to be better than we had seen historically in patients refractory/ intolerant to bortezomib and IMiDs, highlighting the increased treatment options available for these patients. However, there is decreasing response rate to sequential regimens highlighting the development of drug resistance. The data provides a bench mark for comparison of new therapies that are being evaluated in this disease. Table Table. Disclosures Dimopoulos: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Genesis: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Kastritis:Takeda: Consultancy, Honoraria; Genesis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Terpos:BMS: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Celgene: Honoraria; Takeda: Consultancy, Honoraria; Genesis: Consultancy, Honoraria, Other: Travel expenses; Amgen: Consultancy, Honoraria, Other: Travel expenses, Research Funding; Novartis: Honoraria. Hillengass:Sanofi: Research Funding; Novartis: Research Funding; Amgen: Consultancy, Honoraria; BMS: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria. Leleu:TEVA: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; LeoPharma: Honoraria; Amgen: Honoraria; Bristol-Myers Squibb: Honoraria; Pierre Fabre: Honoraria; Celgene: Honoraria; Novartis: Honoraria; Takeda: Honoraria. Oriol:Janssen: Honoraria, Other: Expert board committee; Amgen: Honoraria, Other: Expert board committee. Cavo:Celgene: Consultancy, Honoraria; Millennium: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Mateos:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Vij:Shire: Consultancy; Takeda: Consultancy, Research Funding; Jazz: Consultancy; Karyopharma: Consultancy; Janssen: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Bristol-Myers Squibb: Consultancy; Amgen: Consultancy, Research Funding. Lokhorst:Genmab: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. van de Donk:Amgen: Research Funding; Janssen: Research Funding; BMS: Research Funding; Celgene: Research Funding. Mark:Onyx: Research Funding, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Ludwig:Amgen: Research Funding, Speakers Bureau; Takeda: Research Funding, Speakers Bureau; BMS: Speakers Bureau; Janssen: Speakers Bureau. Jagannath:Novartis: Consultancy; Janssen: Consultancy; Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Merck: Consultancy. Usmani:Array: Research Funding; Britsol-Myers Squibb: Consultancy, Research Funding; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Speakers Bureau. Dytfeld:Janssen Poland: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees. Moreau:Novartis: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Speakers Bureau. Lee:Amgen: Membership on an entity's Board of Directors or advisory committees. Shustik:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. de la Rubia:Celgene: Consultancy; Bristol Myers: Consultancy; Amgen,: Consultancy; Janssen: Consultancy. Durie:Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy.

Published
2017

22. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial

Author

Michele Cavo, Laurent Garderet, Meletios A. Dimopoulos, Hartmut Goldschmidt, Valentina Ivanova, Philippe Moreau, Pieter Sonneveld, Xiaoyan Yu, Antonio Palumbo, Lars Sternas, Lionel Karlin, Steve Schey, Anne Banos, Andrew R. Belch, Kijoung Song, Joaquin Martinez-Lopez, Albert Oriol, Christopher T. Chen, Michel Delforge, Jesús F. San Miguel, Katja Weisel, Christian Jacques, Mohamed H. Zaki, Martha Q. Lacy, Adrian Alegre, San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, Karlin L, Goldschmidt H, Banos A, Oriol A, Alegre A, Chen C, Cavo M, Garderet L, Ivanova V, Martinez-Lopez J, Belch A, Palumbo A, Schey S, Sonneveld P, Yu X, Sternas L, Jacques C, Zaki M, Dimopoulos M, Hematology, Cell biology, and Celgene

Subjects
Male, medicine.medical_specialty, Population, pomalidomide, Gastroenterology, Dexamethasone, Ixazomib, chemistry.chemical_compound, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Humans, Medicine, Elotuzumab, education, Multiple myeloma, Aged, Neoplasm Staging, Lenalidomide, Salvage Therapy, education.field_of_study, business.industry, Bortezomib, Prognosis, medicine.disease, Pomalidomide, Thalidomide, Surgery, Survival Rate, Oncology, chemistry, Drug Resistance, Neoplasm, Female, Neoplasm Recurrence, Local, Multiple Myeloma, business, Follow-Up Studies, medicine.drug
Abstract

[Background]: Few effective treatments exist for patients with refractory or relapsed and refractory multiple myeloma not responding to treatment with bortezomib and lenalidomide. Pomalidomide alone has shown limited efficacy in patients with relapsed multiple myeloma, but synergistic effects have been noted when combined with dexamethasone. We compared the efficacy and safety of pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone in these patients. [Methods]: This multicentre, open-label, randomised phase 3 trial was undertaken in Australia, Canada, Europe, Russia, and the USA. Patients were eligible if they had been diagnosed with refractory or relapsed and refractory multiple myeloma, and had failed at least two previous treatments of bortezomib and lenalidomide. They were assigned in a 2:1 ratio with a validated interactive voice and internet response system to either 28 day cycles of pomalidomide (4 mg/day on days 1-21, orally) plus low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally) or high-dose dexamethasone (40 mg/day on days 1-4, 9-12, and 17-20, orally) until disease progression or unacceptable toxicity. Stratification factors were age (≤75 years vs >75 years), disease population (refractory vs relapsed and refractory vs bortezomib intolerant), and number of previous treatments (two vs more than two). The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01311687, and with EudraCT, number 2010-019820-30. [Findings]: The accrual for the study has been completed and the analyses are presented. 302 patients were randomly assigned to receive pomalidomide plus low-dose dexamethasone and 153 high-dose dexamethasone. After a median follow-up of 10·0 months (IQR 7·2-13·2), median PFS with pomalidomide plus low-dose dexamethasone was 4·0 months (95% CI 3·6-4·7) versus 1·9 months (1·9-2·2) with high-dose dexamethasone (hazard ratio 0·48 [95% CI 0·39-0·60]; p, Funding: Celgene Corporation.

Published
2013

23. European Perspective on Multiple Myeloma Treatment Strategies: Update Following Recent Congresses

Author

Hervé Avet-Loiseau, Johannes Drach, Urs Hess, Jesús F. San-Miguel, Hartmut Goldschmidt, Pieter Sonneveld, Joan Bladé, Javier de la Rubia, Faith E. Davies, Meletios A. Dimopoulos, Miklós Udvardy, Philippe Moreau, Ulf-Henrik Mellqvist, Thierry Facon, Hermann Einsele, Heinz Ludwig, Jamie Cavenagh, Sosana Delimpasi, Mario Boccadoro, Pia Sondergeld, Michele Cavo, Antonio Palumbo, Hematology, Ludwig H, Avet-Loiseau H, Bladé J, Boccadoro M, Cavenagh J, Cavo M, Davies F, de la Rubia J, Delimpasi S, Dimopoulos M, Drach J, Einsele H, Facon T, Goldschmidt H, Hess U, Mellqvist UH, Moreau P, San-Miguel J, Sondergeld P, Sonneveld P, Udvardy M, and Palumbo A.

Subjects
novel agent, Cancer Research, medicine.medical_specialty, Alternative medicine, Antineoplastic Agents, Disease, Pharmacology, Bortezomib, Academia-Pharma Intersect, medicine, Humans, Intensive care medicine, Lenalidomide, Multiple myeloma, business.industry, Perspective (graphical), Congresses as Topic, medicine.disease, Boronic Acids, Thalidomide, Europe, Treatment Outcome, Oncology, Pyrazines, Treatment strategy, Erratum, Multiple Myeloma, business, medicine.drug
Abstract

et al., The management of multiple myeloma has undergone profound changes over the recent past as a result of advances in our understanding of the disease biology as well as improvements in treatment and supportive care strategies. Notably, recent years have seen a surge in studies incorporating the novel agents thalidomide, bortezomib, and lenalidomide into treatment for different disease stages and across different patient groups. This article presents an update to a previous review of European treatment practices and is based on discussions during an expert meeting that was convened to review novel agent data published or presented at medical meetings until the end of 2011 and to assess their impact on treatment strategies. ©AlphaMed Press.

Published
2012

24. Management of treatment-emergent peripheral neuropathy in multiple myeloma

Author

Giampaolo Merlini, Peter M. Voorhees, Sagar Lonial, Amitabha Mazumder, Michele Cavo, M.V. Mateos, Angela Palumbo, Sundar Jagannath, David S. Siegel, Je-Hwan Lee, Meletios A. Dimopoulos, J L Harousseau, Kenneth C. Anderson, Saad Z. Usmani, David H. Vesole, E. Terpos, Michel Delforge, Nikhil C. Munshi, Raymond L. Comenzo, Philippe Moreau, Patrick Y. Wen, Brian G.M. Durie, Gareth J. Morgan, S V Rajkumar, Meral Beksac, Joost L M Jongen, J F San Miguel, O. Sezer, J. Bladé, Wee Joo Chng, Ruben Niesvizky, Hervé Avet-Loiseau, Robert Z. Orlowski, Paul G. Richardson, H. Einsele, J. J. Lahuerta, Pieter Sonneveld, Richardson PG, Delforge M, Beksac M, Wen P, Jongen JL, Sezer O, Terpos E, Munshi N, Palumbo A, Rajkumar SV, Harousseau JL, Moreau P, Avet-Loiseau H, Lee JH, Cavo M, Merlini G, Voorhees P, Chng WJ, Mazumder A, Usmani S, Einsele H, Comenzo R, Orlowski R, Vesole D, Lahuerta JJ, Niesvizky R, Siegel D, Mateos MV, Dimopoulos M, Lonial S, Jagannath S, Bladé J, Miguel JS, Morgan G, Anderson KC, Durie BG, Sonneveld P., Neurology, and Hematology

Subjects
Oncology, Cancer Research, medicine.medical_specialty, Peripheral neuropathy, Pharmacology, Bortezomib, MULTIPLE MYELOMA, Internal medicine, medicine, Humans, Immunologic Factors, Multiple myeloma, Dose Modification, business.industry, Incidence, Peripheral Nervous System Diseases, Hematology, medicine.disease, Boronic Acids, Discontinuation, Thalidomide, Early Diagnosis, Pyrazines, Etiology, business, Complication, Proteasome Inhibitors, medicine.drug
Abstract

Peripheral neuropathy (PN) is one of the most important complications of multiple myeloma (MM) treatment. PN can be caused by MM itself, either by the effects of the monoclonal protein or in the form of radiculopathy from direct compression, and particularly by certain therapies, including bortezomib, thalidomide, vinca alkaloids and cisplatin. Clinical evaluation has shown that up to 20% of MM patients have PN at diagnosis and as many as 75% may experience treatment-emergent PN during therapy. The incidence, symptoms, reversibility, predisposing factors and etiology of treatment-emergent PN vary among MM therapies, with PN incidence also affected by the dose, schedule and combinations of potentially neurotoxic agents. Effective management of treatment-emergent PN is critical to minimize the incidence and severity of this complication, while maintaining therapeutic efficacy. Herein, the state of knowledge regarding treatment-emergent PN in MM patients and current management practices are outlined, and recommendations regarding optimal strategies for PN management during MM treatment are provided. These strategies include early and regular monitoring with neurological evaluation, with dose modification and treatment discontinuation as indicated. Areas requiring further research include the development of MM-specific, patient-focused assessment tools, pharmacogenomic analysis of patient DNA, and trials to assess the efficacy of pharmacological interventions.

Published
2012

25. Multiple myeloma treatment strategies with novel agents in 2011: A European perspective

Author

Martin Kropff, Joan Bladé, Hila Magen-Nativ, Meletios A. Dimopoulos, Pieter Sonneveld, Miklós Udvardy, Pia Sondergeld, Heinz Ludwig, Michel Delforge, Antonio Palumbo, Johannes Drach, Torben Plesner, Hermann Einsele, Vernon J. Louw, Jamie Cavenagh, Michele Cavo, Urs Hess, Meral Beksac, Jean Luc Harousseau, Fernando Leal da Costa, Hareth Nahi, Thierry Facon, Jesús F. San-Miguel, Hartmut Goldschmidt, Larisa P. Mendeleeva, Ludwig H., Beksac M., Bladé J., Cavenagh J., Cavo M., Delforge M., Dimopoulos M., Drach J., Einsele H., Facon T., Goldschmidt H., Harousseau J.L., Hess U., Kropff M., Leal da Costa F., Louw V., Magen-Nativ H., Mendeleeva L., Nahi H., Plesner T., San-Miguel J., Sonneveld P., Udvardy M., Sondergeld P., Palumbo A., Hematology, and Radiology & Nuclear Medicine

Subjects
Cancer Research, medicine.medical_specialty, Evidence-based practice, Comorbidity, Disease-Free Survival, law.invention, Bortezomib, Randomized controlled trial, law, Academia-Pharma Intersect, Antineoplastic Combined Chemotherapy Protocols, medicine, Autologous transplantation, Humans, Intensive care medicine, Lenalidomide, Multiple myeloma, business.industry, Perspective (graphical), Age Factors, novel agents, Congresses as Topic, medicine.disease, Boronic Acids, Thalidomide, Europe, Treatment Outcome, Oncology, Evidence-Based Practice, Pyrazines, Immunology, business, Multiple Myeloma, medicine.drug, Stem Cell Transplantation
Abstract

The arrival of the novel agents thalidomide, bortezomib, and lenalidomide has significantly changed our approach to the management of multiple myeloma and, importantly, patient outcomes have improved. These agents have been investigated intensively in different treatment settings, providing us with data to make evidence-based decisions regarding the optimal management of patients. This review is an update to a previous summary of European treatment practices that examines new data that have been published or presented at congresses up to the end of 2010 and assesses their impact on treatment practices. © AlphaMed Press., Advisory Board meeting supported by Janssen Pharmaceutical Companies of Johnson and Johnson in Europe, Middle East, and Africa (EMEA). Unrestricted educational grant provided by Janssen Pharmaceutical Companies of Johnson and Johnson in the EMEA to assist with editorial support.

Published
2011

26. Treatment of relapsed and refractory multiple myeloma in the era of novel agents

Author

Hervé Avet-Loiseau, Hans Erik Johnsen, Steve Schey, Gareth J. Morgan, Michele Cavo, Jesús F. San-Miguel, Hartmut Goldschmidt, Niels W.C.J. van de Donk, Joan Bladé, Meletios A. Dimopoulos, Henk M. Lokhorst, Martin Kropff, Hermann Einsele, Heinz Ludwig, Pieter Sonneveld, Antonio Palumbo, Hematology, Radiology & Nuclear Medicine, van de Donk N.W., Lokhorst H.M., Dimopoulos M., Cavo M., Morgan G., Einsele H., Kropff M., Schey S., Avet-Loiseau H., Ludwig H., Goldschmidt H., Sonneveld P., Johnsen H.E., Bladé J., San-Miguel J.F., and Palumbo A.

Subjects
novel agent, Oncology, medicine.medical_specialty, Antineoplastic Agents, Bortezomib, Autologous stem-cell transplantation, Refractory, immune system diseases, Refractory disease, hemic and lymphatic diseases, Internal medicine, medicine, Humans, Immunologic Factors, Radiology, Nuclear Medicine and imaging, Lenalidomide, Multiple myeloma, business.industry, Standard treatment, Relapse treatment, General Medicine, medicine.disease, Thalidomide, Surgery, Regimen, Treatment Outcome, Neoplasm Recurrence, Local, business, Multiple Myeloma, guideline, Proteasome Inhibitors, medicine.drug
Abstract

The introduction of the Immunomodulatory drugs (IMiDs) and proteasome inhibitors, used either as a single-agent or combined with classic anti-myeloma therapies, has improved the outcome for patients with relapsed myeloma. However, there is currently no generally accepted standard treatment for relapsed/refractory myeloma patients, partly because of the absence of trials comparing the efficacy of the novel agents in relapsed/refractory myeloma. Choice of a new treatment regimen depends on both patient and disease-specific characteristics. A lenalidomide-based regimen is the first choice in patients with neuropathy, while bortezomib has the highest efficacy in patients with renal insufficiency and is not associated with increased risk of thromboembolism. A second autologous stem cell transplantation (auto-SCT) can be applied in patients with a progression-free period of >= 18-24 months after the first auto-SCT. In high-risk relapse such as occurring early after auto-SCT consolidation with allogeneic SCT can be considered. In this review we provide an overview of the various salvage regimens and give recommendations for treatment of patients with relapsed/refractory myeloma in different clinical settings. (C) 2010 Elsevier Ltd. All rights reserved.

Published
2010

27. Current multiple myeloma treatment strategies with novel agents: a European perspective

Author

Meletios A. Dimopoulos, Torben Plesner, Martin Kropff, Larisa P. Mendeleeva, Michele Cavo, Mario Boccadoro, Thierry Facon, Gareth J. Morgan, Pia Sondergeld, Joan Bladé, Antonio Palumbo, Pieter Sonneveld, Ofer Shpilberg, Meral Beksac, Hermann Einsele, Jesús F. San Miguel, Hartmut Goldschmidt, Nicolas Ketterer, Heinz Ludwig, Jamie Cavenagh, Johannes Drach, Urs Hess, Sonja Zweegman, Jean-Luc Harousseau, Ludwig H, Beksac M, Bladé J, Boccadoro M, Cavenagh J, Cavo M, Dimopoulos M, Drach J, Einsele H, Facon T, Goldschmidt H, Harousseau JL, Hess U, Ketterer N, Kropff M, Mendeleeva L, Morgan G, Palumbo A, Plesner T, San Miguel J, Shpilberg O, Sondergeld P, Sonneveld P, Zweegman S., Hematology, CCA - Innovative therapy, and Radiology & Nuclear Medicine

Subjects
Oncology, Melphalan, Cancer Research, medicine.medical_specialty, Decision Making, Antineoplastic Agents, Pharmacology, Academia–Pharma Intersect, Bortezomib, Prednisone, immune system diseases, Multiple myeloma, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Transplantation, Homologous, Lenalidomide, Chromosome Aberrations, Clinical Trials as Topic, business.industry, Decision Trees, medicine.disease, Boronic Acids, Thalidomide, Transplantation, Regimen, Myelomas, Pyrazines, Kidney Failure, Chronic, Neoplasm Recurrence, Local, business, medicine.drug, Stem Cell Transplantation
Abstract

This review presents an overview of the most recent data using the novel agents thalidomide, bortezomib, and lenalidomide in the treatment of multiple myeloma and summarizes European treatment practices incorporating these novel agents., The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents.

Published
2010

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