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1. Overall Survival with Daratumumab, Lenalidomide, and Dexamethasone in Previously Treated Multiple Myeloma (POLLUX): A Randomized, Open-Label, Phase III Trial

Author

Dimopoulos, M.A. Oriol, A. Nahi, H. San-Miguel, J. Bahlis, N.J. Usmani, S.Z. Rabin, N. Orlowski, R.Z. Suzuki, K. Plesner, T. Yoon, S.-S. Ben Yehuda, D. Richardson, P.G. Goldschmidt, H. Reece, D. Ahmadi, T. Qin, X. Garvin Mayo, W. Gai, X. Carey, J. Carson, R. Moreau, P. and Dimopoulos, M.A. Oriol, A. Nahi, H. San-Miguel, J. Bahlis, N.J. Usmani, S.Z. Rabin, N. Orlowski, R.Z. Suzuki, K. Plesner, T. Yoon, S.-S. Ben Yehuda, D. Richardson, P.G. Goldschmidt, H. Reece, D. Ahmadi, T. Qin, X. Garvin Mayo, W. Gai, X. Carey, J. Carson, R. Moreau, P.

Abstract

PURPOSEWith the initial analysis of POLLUX at a median follow-up of 13.5 months, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly prolonged progression-free survival versus lenalidomide and dexamethasone (Rd) alone in patients with relapsed or refractory multiple myeloma (RRMM). We report updated efficacy and safety results at the time of final analysis for overall survival (OS).METHODSPOLLUX was a multicenter, randomized, open-label, phase III study during which eligible patients with ≥ 1 line of prior therapy were randomly assigned 1:1 to D-Rd or Rd until disease progression or unacceptable toxicity. After positive primary analysis and protocol amendment, patients receiving Rd were offered daratumumab monotherapy after disease progression.RESULTSSignificant OS benefit was observed with D-Rd (hazard ratio, 0.73; 95% CI, 0.58 to 0.91; P =.0044) at a median (range) follow-up of 79.7 months (0.0-86.5). The median OS was 67.6 months for D-Rd compared with 51.8 months for Rd. Prespecified analyses demonstrated an improved OS with D-Rd versus Rd in most subgroups, including patients age ≥ 65 years and patients with one, two, or three prior lines of therapy, International Staging System stage III disease, high-risk cytogenetic abnormalities, and refractoriness to their last prior line of therapy or a proteasome inhibitor. The most common (≥ 10%) grade 3/4 treatment-emergent adverse events with D-Rd versus Rd were neutropenia (57.6% v 41.6%), anemia (19.8% v 22.4%), pneumonia (17.3% v 11.0%), thrombocytopenia (15.5% v 15.7%), and diarrhea (10.2% v 3.9%).CONCLUSIOND-Rd significantly extended OS versus Rd alone in patients with RRMM. To our knowledge, for the first time, our findings, together with the OS benefit observed with daratumumab plus bortezomib and dexamethasone in the phase III CASTOR trial, demonstrate OS improvement with daratumumab-containing regimens in RRMM (ClinicalTrials.gov identifier: NCT02076009 [POLLUX]). © American So

Published
2023

2. P05: DARATUMUMAB PLUS LENALIDOMIDE AND DEXAMETHASONE VERSUS LENALIDOMIDE AND DEXAMETHASONE ALONE IN PATIENTS WITH PREVIOUSLY TREATED MULTIPLE MYELOMA: OVERALL SURVIVAL RESULTS FROM THE PHASE 3 POLLUX TRIAL

Author

Dimopoulos, MA, primary, Oriol, A, additional, Nahi, H, additional, San-Miguel, J, additional, Bahlis, NJ, additional, Usmani, SZ, additional, Rabin, N, additional, Orlowski, RZ, additional, Suzuki, K, additional, Plesner, T, additional, Yoon, SS, additional, Ben Yehuda, D, additional, Richardson, PG, additional, Goldschmidt, H, additional, Reece, D, additional, Ahmadi, T, additional, Qin, X, additional, Garvin Mayo, W, additional, Gai, X, additional, Carey, J, additional, Carson, R, additional, and Moreau, P, additional

Published
2022
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6. Health-related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial

Author

Plesner, T, Dimopoulos, MA, Oriol, A, San-Miguel, J, Bahlis, NJ, Rabin, N, Suzuki, K, Yoon, SS, Ben-Yehuda, D, Cook, G, Goldschmidt, H, Grosicki, S, Qin, X, Fastenau, J, Garvin, W, Carson, R, Renaud, T, and Gries, KS

Subjects
relapsed, refractory multiple myeloma, reported outcomes, POLLUX, daratumumab, health&#8208, related quality of life, patient&#8208
Abstract

In the phase 3 POLLUX trial, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma (RRMM) compared with lenalidomide and dexamethasone (Rd) alone. Here, we present patient-reported outcomes (PROs) from POLLUX, assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaires. Changes from baseline are presented as least-squares mean changes with 95% confidence intervals (CIs) derived from a mixed-effects model. PRO assessment compliance rates were high and similar in both D-Rd and Rd groups through cycle 40 (week 156). In this on-treatment analysis, mean changes from baseline were significantly greater in EORTC QLQ-C30 global health status, physical functioning, and pain scores in the D-Rd group versus the Rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health-related quality of life (HRQoL). Subgroup results were similar to those in the overall population. In the POLLUX study, baseline HRQoL was maintained with prolonged D-Rd treatment. These findings complement the sustained and significant improvement in progression-free survival observed with D-Rd and supports its use in patients with RRMM. Clinical trial registration: NCT02076009.

Published
2021

7. Health-related quality of life in patients with relapsed or refractory multiple myeloma: treatment with daratumumab, lenalidomide, and dexamethasone in the phase 3 POLLUX trial

Author

Plesner, T. Dimopoulos, M.A. Oriol, A. San-Miguel, J. Bahlis, N.J. Rabin, N. Suzuki, K. Yoon, S.-S. Ben-Yehuda, D. Cook, G. Goldschmidt, H. Grosicki, S. Qin, X. Fastenau, J. Garvin, W. Carson, R. Renaud, T. Gries, K.S.

Subjects
humanities
Abstract

In the phase 3 POLLUX trial, daratumumab in combination with lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma (RRMM) compared with lenalidomide and dexamethasone (Rd) alone. Here, we present patient-reported outcomes (PROs) from POLLUX, assessed using the validated European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30-item (EORTC QLQ-C30) and the EuroQol 5-dimensional descriptive system (EQ-5D-5L) questionnaires. Changes from baseline are presented as least-squares mean changes with 95% confidence intervals (CIs) derived from a mixed-effects model. PRO assessment compliance rates were high and similar in both D-Rd and Rd groups through cycle 40 (week 156). In this on-treatment analysis, mean changes from baseline were significantly greater in EORTC QLQ-C30 global health status, physical functioning, and pain scores in the D-Rd group versus the Rd group at multiple time points; however, magnitude of changes was low, suggesting no meaningful impact on health-related quality of life (HRQoL). Subgroup results were similar to those in the overall population. In the POLLUX study, baseline HRQoL was maintained with prolonged D-Rd treatment. These findings complement the sustained and significant improvement in progression-free survival observed with D-Rd and supports its use in patients with RRMM. Clinical trial registration: NCT02076009. © 2021 British Society for Haematology and John Wiley & Sons Ltd.

Published
2021

12. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial

Author

Richardson, Paul G, Oriol, Albert, Beksac, Meral, Liberati, Anna Marina, Galli, Monica, Schjesvold, Fredrik, Lindsay, Jindriska, Weisel, Katja, White, Darrell, Facon, Thierry, San Miguel, Jesus, Sunami, Kazutaka, O'Gorman, Peter, Sonneveld, Pieter, Robak, Pawel, Semochkin, Sergey, Schey, Steve, Yu, Xin, Doerr, Thomas, Bensmaine, Amine, Biyukov, Tsvetan, Peluso, Teresa, Zaki, Mohamed, Anderson, Kenneth, Dimopoulos, Meletios, OPTIMISMM trial investigators, Abildgaard N, Adler H, Altuntas F, Akay OM, 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 IW, 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 MM, 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 MT, Kuriakose P, Larocca A, Lauri B, Leleu X, Lucio P, Luppi M, Mangiacavalli S, Mariette C, Matsue K, Mellqvist UH, Mendeleeva L, Meshad M, Miller C, Mohrbacher A, Moreau P, Morelli AM, 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 AA, 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 HÜ, Vapaatalo M, Vassilopoulos G, Verma A, Vidito S, Viterbo L, Vural F, Wang XS, Yağci M, Yee A., Richardson, Paul G, Oriol, Albert, Beksac, Meral, Liberati, Anna Marina, Galli, Monica, Schjesvold, Fredrik, Lindsay, Jindriska, Weisel, Katja, White, Darrell, Facon, Thierry, San Miguel, Jesu, Sunami, Kazutaka, O'Gorman, Peter, Sonneveld, Pieter, Robak, Pawel, Semochkin, Sergey, Schey, Steve, Yu, Xin, Doerr, Thoma, Bensmaine, Amine, Biyukov, Tsvetan, Peluso, Teresa, Zaki, Mohamed, Anderson, Kenneth, Dimopoulos, Meletio, OPTIMISMM trial investigator, Abildgaard N, Adler H, Altuntas F, Akay OM, 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 IW, 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 MM, 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 MT, Kuriakose P, Larocca A, Lauri B, Leleu X, Lucio P, Luppi M, Mangiacavalli S, Mariette C, Matsue K, Mellqvist UH, Mendeleeva L, Meshad M, Miller C, Mohrbacher A, Moreau P, Morelli AM, 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 AA, 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 HÜ, Vapaatalo M, Vassilopoulos G, Verma A, Vidito S, Viterbo L, Vural F, Wang XS, Yağci M, Yee A., and Hematology

Subjects
Oncology, Adult, Male, medicine.medical_specialty, Adolescent, Population, Dexamethasone, Bortezomib, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, education, Survival rate, Lenalidomide, Multiple myeloma, Aged, Salvage Therapy, education.field_of_study, business.industry, Pomalidomide, bortezomib, dexamethasone, Middle Aged, Pomalidomide, medicine.disease, Prognosis, Thalidomide, Survival Rate, Regimen, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Female, Neoplasm Recurrence, Local, business, Multiple Myeloma, 030215 immunology, medicine.drug, Follow-Up Studies
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 beta(2) microglobulin at screening. Bortezomib (1.3 mg/m(2)) 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

Published
2019
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13. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial

Author

Mateos, Maria-Victoria, Blacklock, Hilary, Schjesvold, Fredrik, Oriol, Albert, Simpson, David, George, Anupkumar, Goldschmidt, Hartmut, Larocca, Alessandra, Chanan-Khan, Asher, Sherbenou, Daniel, Avivi, Irit, Benyamini, Noam, Iida, Shinsuke, Matsumoto, Morio, Suzuki, Kenshi, Ribrag, Vincent, Usmani, Saad Z, Jagannath, Sundar, Ocio, Enrique M, Rodriguez-Otero, Paula, San Miguel, Jesus, Kher, Uma, Farooqui, Mohammed, Liao, Jason, Marinello, Patricia, Lonial, Sagar, KEYNOTE-183 Investigators, Nicol A, Grigoriadis G, Catalano J, LeBlanc R, Elemary M, Bahlis N, Facon T, Karlin L, Ribrag V, Attal M, Goldschmidt H, Engelhardt M, Weisel K, Mackensen A, Nagler A, Ben Yehuda D, Avivi I, Benyamini N, Magen-Nativ H, Palumbo A, Cavo M, Tobinai K, Iida S, Chou T, Suzuki K, Kosugi H, Taniwaki M, Sunami K, Matsumoto M, Ando K, Ganly P, Blacklock H, Simpson D, George A, Schjesvold F, Gjertsen B, Lahuerta J, Blade J, Oriol Rocafiguera A, Mateos M, Rodriguez-Otero P, Larson S, Atanackovic D, Devarakonda S, Bitran J, Zonder J, Morganstein N, Hay M, Chanan-Khan A, Saylors G, Kio E, Oliff I, Kirkel D, Shtivelband M, Yuen C, Yee A, Shah J, Htut M, Raza S, Chhabra S, Stiff P, Hari P, Bank B, Malek E, Gasparetto C, Faroun Y, Sherbenou D, Kreisle W, Singhal S, Rosenblatt J, Usmani S, Lee W, Safah H, Lutzky J, Suh J, Pan D, Baron A, Manges R, Steis R, Oliveira M, Moreb J, Callander N, Anz B, Raptis A, Stampleman L, Melear J, Boyd T, Garbo L, Klein L, Shao S, Lyons R, McIntyre K, Tarantolo S, Yasenchak C, Yimer H., Mateos, Maria-Victoria, Blacklock, Hilary, Schjesvold, Fredrik, Oriol, Albert, Simpson, David, George, Anupkumar, Goldschmidt, Hartmut, Larocca, Alessandra, Chanan-Khan, Asher, Sherbenou, Daniel, Avivi, Irit, Benyamini, Noam, Iida, Shinsuke, Matsumoto, Morio, Suzuki, Kenshi, Ribrag, Vincent, Usmani, Saad Z, Jagannath, Sundar, Ocio, Enrique M, Rodriguez-Otero, Paula, San Miguel, Jesu, Kher, Uma, Farooqui, Mohammed, Liao, Jason, Marinello, Patricia, Lonial, Sagar, KEYNOTE-183 Investigator, and Nicol A, Grigoriadis G, Catalano J, LeBlanc R, Elemary M, Bahlis N, Facon T, Karlin L, Ribrag V, Attal M, Goldschmidt H, Engelhardt M, Weisel K, Mackensen A, Nagler A, Ben Yehuda D, Avivi I, Benyamini N, Magen-Nativ H, Palumbo A, Cavo M, Tobinai K, Iida S, Chou T, Suzuki K, Kosugi H, Taniwaki M, Sunami K, Matsumoto M, Ando K, Ganly P, Blacklock H, Simpson D, George A, Schjesvold F, Gjertsen B, Lahuerta J, Blade J, Oriol Rocafiguera A, Mateos M, Rodriguez-Otero P, Larson S, Atanackovic D, Devarakonda S, Bitran J, Zonder J, Morganstein N, Hay M, Chanan-Khan A, Saylors G, Kio E, Oliff I, Kirkel D, Shtivelband M, Yuen C, Yee A, Shah J, Htut M, Raza S, Chhabra S, Stiff P, Hari P, Bank B, Malek E, Gasparetto C, Faroun Y, Sherbenou D, Kreisle W, Singhal S, Rosenblatt J, Usmani S, Lee W, Safah H, Lutzky J, Suh J, Pan D, Baron A, Manges R, Steis R, Oliveira M, Moreb J, Callander N, Anz B, Raptis A, Stampleman L, Melear J, Boyd T, Garbo L, Klein L, Shao S, Lyons R, McIntyre K, Tarantolo S, Yasenchak C, Yimer H.

Subjects
Male, medicine.medical_specialty, Pembrolizumab, Antibodies, Monoclonal, Humanized, Dexamethasone, Drug Administration Schedule, 03 medical and health sciences, Pembrolizumab, pomalidomide, dexamethasone, KEYNOTE-183, 0302 clinical medicine, Recurrence, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Progression-free survival, Survival rate, Multiple myeloma, Aged, Proportional Hazards Models, Lenalidomide, Aged, 80 and over, Performance status, business.industry, Hematology, medicine.disease, Pomalidomide, Interim analysis, Progression-Free Survival, Thalidomide, Survival Rate, Myocarditis, Editorial Commentary, Treatment Outcome, Stevens-Johnson Syndrome, 030220 oncology & carcinogenesis, Female, Multiple Myeloma, business, 030215 immunology, medicine.drug
Abstract

Summary Background Pomalidomide and dexamethasone is a standard of care for patients with multiple myeloma in whom bortezomib and lenalidomide treatment has failed. KEYNOTE-183 assessed efficacy and safety of pomalidomide and dexamethasone with or without pembrolizumab in patients with relapsed or refractory multiple myeloma. Here, we present the findings of an unplanned, ad-hoc interim analysis at the request of the US Food and Drug Administration (FDA). Methods KEYNOTE-183 was a randomised, open-label, phase 3 trial done at 97 medical centres across 11 countries (Australia, Canada, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Spain, and USA). Patients aged at least 18 years with multiple myeloma, an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, previously treated with at least two lines of therapy (excluding pomalidomide) and refractory to the last line were randomly assigned 1:1 to the pembrolizumab plus pomalidomide and dexamethasone group or the pomalidomide and dexamethasone group via an interactive voice response or integrated web response system. Patients received oral pomalidomide 4 mg daily on days 1–21 and oral low-dose dexamethasone 40 mg on days 1, 8, 15, and 22 in 28-day cycles, with or without intravenous pembrolizumab 200 mg every 3 weeks. The dual primary endpoints were progression-free survival and overall survival. Efficacy was assessed in all randomly assigned patients and safety was assessed in patients who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov , number NCT02576977 , and it is closed for accrual. Findings Between Jan 18, 2016, and June 7, 2017, 249 patients were randomly assigned to either the pembrolizumab plus pomalidomide and dexamethasone group (n=125) or the pomalidomide and dexamethasone group (n=124). On July 3, 2017, the FDA established that risks associated with the triple combination outweighed benefits and halted the study. Median follow-up was 8·1 months (IQR 4·5–10·9). Median progression-free survival was 5·6 months (95% CI 3·7–7·5) in the pembrolizumab plus pomalidomide and dexamethasone group versus 8·4 months (5·9–not reached) in the pomalidomide and dexamethasone group; progression-free survival estimates at 6 months were 48% (95% CI 37–58) versus 60% (49–69) at 6 months (hazard ratio [HR] 1·53; 95% CI 1·05–2·22; p=0·98). Median overall survival was not reached (95% CI 12·9–not reached) versus 15·2 months (12·7–not reached; HR 1·61; 95% CI 0·91–2·85; p=0·95); overall survival estimates at 6 months were 82% (95% CI 74–88) versus 90% (82–95). Serious adverse events occurred in 75 (63%) of 120 patients in the pembrolizumab plus pomalidomide and dexamethasone group versus 56 (46%) of 121 patients in the pomalidomide and dexamethasone group. Four (3%) treatment-related deaths occurred in the pembrolizumab plus pomalidomide and dexamethasone group (one each of unknown cause, neutropenic sepsis, myocarditis, and Stevens–Johnson syndrome); myocarditis and Stevens-Johnson syndrome were considered related to pembrolizumab. No treatment-related deaths were reported in the pomalidomide and dexamethasone group. Interpretation The results from this unplanned, FDA-requested, interim analysis showed that the benefit–risk profile of pembrolizumab plus pomalidomide and dexamethasone is unfavourable for patients with relapsed or refractory multiple myeloma. Funding Merck Sharp & Dohme, a subsidiary of Merck & Co (Kenilworth, NJ, USA).

Published
2019

15. Health-related quality-of-life results from the phase 3 OPTIMISMM study: pomalidomide, bortezomib, and low-dose dexamethasone versus bortezomib and low-dose dexamethasone in relapsed or refractory multiple myeloma

Author

Weisel, K. Dimopoulos, M. Moreau, P. Yagci, M. Larocca, A. Kanate, A.S. Vural, F. Cascavilla, N. Basu, S. Johnson, P. Byeff, P. Hus, M. Rodríguez-Otero, P. Muelduer, E. Anttila, P. Hayden, P.J. Krauth, M.-T. Lucio, P. Ben-Yehuda, D. Mendeleeva, L. Guo, S. Yu, X. Grote, L. Biyukov, T. Dhanasiri, S. Richardson, P.

Subjects
humanities
Abstract

In the randomized phase-3 OPTIMISMM study, the addition of pomalidomide to bortezomib and low-dose dexamethasone (PVd) resulted in significant improvement in progression-free survival (PFS) in lenalidomide-pretreated patients with relapsed or refractory multiple myeloma (RRMM), including lenalidomide refractory patients. Here, we report health-related quality of life (HRQoL) results from this trial. Patients received PVd or Vd in 21-day cycles until disease progression or discontinuation. HRQoL was assessed using the EORTC QLQ-C30, QLQ-MY20, and EQ-5D-3L instruments on day 1 of each treatment cycle. Mean score changes for global QoL, physical functioning, fatigue, side effects of treatment domains, and EQ-5D-3L index were generally stable over time across treatment arms. The proportion of patients who experienced clinically meaningful worsening in global QoL and other domains of interest was similar. These HRQoL results with PVd along with previously demonstrated improvement in PFS vs Vd continue to support its use in patients with RRMM. © 2020 Informa UK Limited, trading as Taylor & Francis Group.

Published
2020

16. Outcome of paraosseous extra-medullary disease in newly diagnosed multiple myeloma patients treated with new drugs

Author

Montefusco, V, Gay, F, Spada, S, De Paoli, L, Di Raimondo, F, Ribolla, R, Musolino, C, Patriarca, F, Musto, P, Galieni, P, Ballanti, S, Nozzoli, C, Cascavilla, N, Ben-Yehuda, D, Nagler, A, Hajek, R, Offidani, M, Liberati, AM, Sonneveld, Pieter, Cavo, M, Corradini, P, Boccadoro, M, Montefusco, V, Gay, F, Spada, S, De Paoli, L, Di Raimondo, F, Ribolla, R, Musolino, C, Patriarca, F, Musto, P, Galieni, P, Ballanti, S, Nozzoli, C, Cascavilla, N, Ben-Yehuda, D, Nagler, A, Hajek, R, Offidani, M, Liberati, AM, Sonneveld, Pieter, Cavo, M, Corradini, P, and Boccadoro, M

Published
2020

19. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial

Author

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

Subjects
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

Published
2019

20. PF602 OUTCOME OF EXTRA-MEDULLARY DISEASE IN NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS TREATED WITH NEW DRUGS

Author

Montefusco, V., primary, Gay, F., additional, Spada, S., additional, De Paoli, L., additional, Raimondo, F. Di, additional, Ribolla, R., additional, Musolino, C., additional, Patriarca, F., additional, Musto, P., additional, Galieni, P., additional, Ballanti, S., additional, Nozzoli, C., additional, Cascavilla, N., additional, Ben-Yehuda, D., additional, Nagler, A., additional, Hajek, R., additional, Offidani, M., additional, Liberati, A.M., additional, Sonneveld, P., additional, Cavo, M., additional, Corradini, P., additional, and Boccadoro, M., additional

Published
2019
Full Text
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21. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed or refractory multiple myeloma previously treated with lenalidomide (OPTIMISMM): a randomised, open-label, phase 3 trial

Author

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 and 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

Published
2019

22. Limited clinical relevance of imaging techniques in the follow-up of patients with advanced chronic lymphocytic leukemia: results of a meta-analysis

Author

Eichhorst, Barbara F, Fischer, Kirsten, Fink, Anna Maria, Elter, Thomas, Wendtner, Clemens M, Goede, Valentin, Bergmann, Manuela, Stilgenbauer, Stephan, Hopfinger, Georg, Ritgen, Matthias, Bahlo, Jasmin, Busch, Raymonde, Hallek, Michael, Oduncu, F, Dreyling, M, Forstpointner, R, Schneller, F, Bogner, C, Peschel, C, Ringshausen, I, Götze, K, Goebeler, Me, Rückle, Lanz, Ritgen, M, Schawitzke, A, Heydrich, B, Kern, K, Böttcher, S, Irmer, S, Strack, U, Borries, V, Klima, Km, Scholz, C, Herold, M, Härtwig, K, Dürig, J, Dührsen, U, Müller Beissenhirtz, H, Noppeney, R, Schüttrumpf, S, Hohloch, K, Binder, C, Hasenkamp, J, Trümper, L, Bäsecke, J, Rieger, M, Witzens Harig, M, Friedrichs, B, Rieger, K, Uharek, L, Kubuschok, B, Murawski, N, Held, G, Zwick, C, Pfreundschuh, M, Fingerle Rowson, G, Reiser, M, Elter, T, Eichhorst, B, Pallasch, C, Hallek, M, Borchmann, P, Hacker, U, Schinkel, S, Wieker, K, Sökler, M, Wolf, Hh, Eucker, J, Staib, P, Schlegel, F, Kropff, M, Kahl, C, Hess, G, Beck, J, Wölfel, T, Bokemeyer, C, Schilling, G, Dierlamm, J, Schüler, F, Busemann, C, Dölken, G, Trendelenburg, Tk, Bühler, A, Stilgenbauer, S, Viardot, A, Greiner, J, Zenz, T, Gaidzik, V, Langer, C, Döhner, H, Werner, I, Dienst, A, Habersang, K, Härtel, N, Leitner, A, Kehrer, G, Middeke, H, Heinisch, K, Adorf, D, Ismer, B, Hering Schubert, C, Jäckle, J, Aulmann, C, Söllner, S, Majunke, P, Fuss, H, Käfer, G, Potenberg, J, Dietrich, G, Hartung, E, Pronath, A, Riedhammer, Fj, Zehrfeld, T, Prümmer, O, Gatter, J, Meier, A, Wattad, M, Heit, W, Sauer, I, Hilgers, K, Geissler, M, Bauer, J, Stein, W, Voigtmann, R, Natt, F, Nickelsen, M, Zeis, M, Schmitz, N, Lange, E, Stoltefuss, A, Schubert, J, Dürk, Ha, Kloke, O, Fauser, A, Roemer, E, Kraut, L, Musch, E, Kohl, S, Link, H, Kirsch, Jf, Schatz, M, Mezger, J, Kempf, B, Heil, G, Derigs, Hg, Roll, C, Kettner, E, Dübbers, Hw, Lutz, L, Hentrich, M, Hoffmann, U, Ibe, M, Falge, C, Schäfer Eckart, K, Rothmann, F, Raghavachar, A, Beckmann, K, Behringer, D, Stauder, H, Hempfling, C, Matzdorff, A, Hähling, D, Kaesberger, Kj, Mück, R, Waladkhani, Ar, Clemens, M, Kraft, J, Ehlert, T, N. N., Schloen, A, Sandritter, B, Scholz, Diekmann, C, Pflüger, Kh, Hausner, G, Fetscher, S, Aulitzky, W, Brugger, W, Frickhofen, N, Fuhr, Lange, C, Lambertz, H, Schulz, L, Schmier, M, Bentz, M, Tauchmann, Gm, Schmidt, M, Meiler, J, Sandmann, M, Kürschner, D, Maier Bay, B, Lindemann, W, Diers, J, Riemeier Sievers, C, Daun, M, Mergenthaler, Hg, Hiller, S, Schirmer, V, Kirchner, H, Langer, W, Günther, B, Gassmann, W, Franke, K, Burghardt, F, Abele, U, Celikel Becker, D, von Weikersthal LF, Brög, G, Hauch, U, Heinrich, B, Brudler, O, Häcker, B, Eckart, Mj, Bolouri, H, Göttler, B, Kindler, M, Zuchold, K, Strohbach, F, Plingen, Ml, Seibt Jung, H, Kirsch, A, Herrenberger, J, Doering, G, von Grünhagen, U, Franke, H, Weniger, J, Kerzel, W, Schmalfeld, M, Rohrberg, R, Hurtz, Hj, Gehbauer, G, Hahnfeld, S, Vehling Kaiser, U, Abenhardt, W, Bosse, D, Böning, L, Schmidt, B, Schick, Hd, Jacobs, G, Stauch, M, Hoffmann, R, Müller, S, Hahn, M, Freier, W, Dietzfelbinger, H, Rassmann, I, Söling, U, Siehl, S, Rudolph, R, Weinert, R, Sauer, A, Meyer, B, Eschenburg, H, Schadeck Gressel, C, Grabenhorst, U, Perker, M, Otremba, B, Reschke, D, Hinrichs, Hf, Zirpel, I, Höring, E, Respondek, M, Köppler, H, Heymanns, J, Weide, R, Hünermund, K, Thiel, C, Reiber, T, Spohn, C, Springer, G, Fiechtner, H, Hübner, A, Kurschel, E, Weiss, J, Schlag, R, Schäfer, E, Hartwich, G, Schmitz, S, Steinmetz, T, Kim, Ts, Lerchenmüller, C, Wehmeyer, J, Laubenstein, Hp, Rendenbach, B, Lebahn, H, Kröning, H, Uhle, R, Balló, H, Gaede, B, Zumbrink, S, Eckert, R, Kamp, T, Reimann, B, Burkhard, O, Mittermüller, J, Hansen, R, Hitz, H, Schliesser, G, Schmitt, Hr, Forstbauer, H, Grundeis, M, Schulze, M, Baldus, M, Lakner, V, Haen, M, Müller, C, Dörfel, S, Göhler, T, Welslau, M, Achtzehn, V, Culmann, H, Gerhardt, S, Ulshöfer, T, Koschuth, A, Schmidt, P, Müller, L, Schneider, M, Koniczek, K, Porowski, P, Glados, M, Knoblich, J, Ben Yehuda, D, Jäger, U, Gaiger, A, Schwarzmeier, J, Nösslinger, T, Smith, M, Patton, N, Gibbons, S, Bouabdallah, R, Gandhi, M, Marlton, P, Mills, T, Angelucci, E, Sorano, Gg, Casula, P, Berneman, Z, Kohser, P, Hudcova Burgetova, A, Machová, R, Papajik, T, Kubová, Z, Fineman, R, Mayer, J, Doubek, M, Brychtova, Y, Ciceri, F, Caligaris Cappio, F, Crocchiolo, R, Dauriac, C, Bernard, M, Escoffre Barbe, M, Lamy, T, Zikesova, E, Karban, J, Salkova, J, Trnený, M, Pytlik, R, Tiley, C, Forsyth, C, Vokurka, S, Koza, V, Van Hoof, A, Selleslag, D, Sebban, C, Baker, B, Belada, D, Jebavy, L, Smolej, L, Pavel, Z, Di Ianni, M, Castaigne, S, Del Poeta, G, Amadori, S, Catalano, J, Ganju, V, Hertzberg, M, Laurenti, L, Dalseg, Am, Bron, D, Morton, J, Durrant, S, Casado, Lf, Theunissen, K, Atias, D, Berkhan, L, Seymour, J, Wolf, M, Bosly, A, Osma Cordoba MM, Portois, C, Jaubert, J, Ferrant, A, Lambert, C, Maerevoet, E, Van den Neste, E, Gadeberg, O, Carney, B, Cannell, P, Eghbali, H, Legouffe, E, Bordessoule, D, Chaury, M, Moreau, S, Pierri, I, Gobbi, M, Berrebi, A, Lishner, M, Yerushazim, R, Yermiaku, T, Kosolov, V, Ambrosetti, Achille, Andreoli, Al, Huguet, F, Laurent, G, Orsucci, L, Forconi, F, Musuraca, G, Zinzani, Pl, Loscertales, J, Mcquillan, A, Cordingley, F, Leahy, M, Cazin, B, Taylor, Mulligan, S, Herbrecht, Cull, G, Seldon, M, Rowlings, P, Ludwig, H, Zojer, N, Solal Céligny, P, Pomponi, F, Savdkova, L, Kozák, T, Christiansen, I, Pérez, I, Campbell, P, Canales Albendea, M, De Paz, R, Arthur, C, Gisselbrecht, C., Eichhorst B.F., Fischer K., Fink A.M., Elter T., Wendtner C.M., Goede V., Bergmann M., Stilgenbauer S., Hopfinger G., Ritgen M., Bahlo J., Busch R., Hallek M., and Zinzani P.L.

Subjects
Male, medicine.medical_specialty, Cyclophosphamide, Chronic lymphocytic leukemia, Immunology, Medizin, Antineoplastic Combined Chemotherapy Protocols, Blood Cell Count, Disease Progression, Disease-Free Survival, Female, Follow-Up Studies, Humans, Leukemia, Lymphocytic, Chronic, B-Cell, Middle Aged, Prognosis, Recurrence, Remission Induction, Tomography, X-Ray Computed, Physical examination, Biochemistry, Chemoimmunotherapy, medicine, Chronic, Tomography, Leukemia, medicine.diagnostic_test, business.industry, B-Cell, Cancer, Cell Biology, Hematology, medicine.disease, Lymphocytic, imaging techniques, X-Ray Computed, Fludarabine, Surgery, chronic lymphocytic leukemia, Radiology, business, Progressive disease, medicine.drug
Abstract

The clinical value of imaging is well established for the follow-up of many lymphoid malignancies but not for chronic lymphocytic leukemia (CLL). A meta-analysis was performed with the dataset of 3 German CLL Study Group phase 3 trials (CLL4, CLL5, and CLL8) that included 1372 patients receiving first-line therapy for CLL. Response as well as progression during follow-up was reassessed according to the National Cancer Institute Working Group1996 criteria. A total of 481 events were counted as progressive disease during treatment or follow-up. Of these, 372 progressions (77%) were detected by clinical symptoms or blood counts. Computed tomography (CT) scans or ultrasound were relevant in 44 and 29 cases (9% and 6%), respectively. The decision for relapse treatment was determined by CT scan or ultrasound results in only 2 of 176 patients (1%). CT scan results had an impact on the prognosis of patients in complete remission only after the administration of conventional chemotherapy but not after chemoimmunotherapy. In conclusion, physical examination and blood count remain the methods of choice for staging and clinical follow-up of patients with CLL as recommended by the International Workshop on Chronic Lymphocytic Leukemia 2008 guidelines. These trials are registered at http://www.isrctn.org as ISRCTN 75653261 and ISRCTN 36294212 and at http://www.clinicaltrials.gov as NCT00281918.

Published
2011
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25. International myeloma working group recommendations for the diagnosis and management of myeloma-related renal impairment

Author

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.

Published
2016

27. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma

Author

Dimopoulos, M.A. Oriol, A. Nahi, H. San-Miguel, J. Bahlis, N.J. Usmani, S.Z. Rabin, N. Orlowski, R.Z. Komarnicki, M. Suzuki, K. Plesner, T. Yoon, S.-S. Ben Yehuda, D. Richardson, P.G. Goldschmidt, H. Reece, D. Lisby, S. Khokhar, N.Z. O'Rourke, L. Chiu, C. Qin, X. Guckert, M. Ahmadi, T. Moreau, P. POLLUX Investigators

Abstract

BACKGROUND: Daratumumab showed promising efficacy alone and with lenalidomide and dexamethasone in a phase 1-2 study involving patients with relapsed or refractory multiple myeloma. METHODS: In this phase 3 trial, we randomly assigned 569 patients with multiple myeloma who had received one or more previous lines of therapy to receive lenalidomide and dexamethasone either alone (control group) or in combination with daratumumab (daratumumab group). The primary end point was progression-free survival. RESULTS: At a median follow-up of 13.5 months in a protocol-specified interim analysis, 169 events of disease progression or death were observed (in 53 of 286 patients [18.5%] in the daratumumab group vs. 116 of 283 [41.0%] in the control group; hazard ratio, 0.37; 95% confidence interval [CI], 0.27 to 0.52; P

Published
2016

29. Practical Considerations for the Use of Daratumumab, a Novel CD38 Monoclonal Antibody, in Myeloma

Author

Moreau, P. Van De Donk, N.W.C.J. Miguel, J.S. Lokhorst, H. Nahi, H. Ben-Yehuda, D. Cavo, M. Cook, G. Delforge, M. Einsele, H. Zweegman, S. Ludwig, H. Driessen, C. Palumbo, A. Facon, T. Plesner, T. Dimopoulos, M. Sondergeld, P. Sonneveld, P. Mateos, M.-V.

Abstract

Monoclonal antibodies (mAbs) are a recent addition to multiple myeloma (MM) therapies and a number of mAbs directed at myeloma cell surface molecules are in development. Daratumumab is a CD38 mAb that has demonstrated substantial activity and good tolerability in four phase I, phase I/II and phase II studies as monotherapy, as well as in combination with current standard treatments in MM. The positive results obtained in the relapsed/refractory setting in patients with advanced-stage disease and in a small number of patients with newly diagnosed disease provide the rationale for the investigation of the agent in a number of ongoing phase III trials. mAbs are generally better tolerated than conventional chemotherapy; however, their use requires other special considerations. Such factors include those common to all mAbs, namely infusion-related reactions, but also factors that are observed with mAbs used in myeloma, such as interference with response assessment, or factors that are related to CD38 mAbs such as daratumumab, for instance blood typing interference. Our review provides an overview of the results from the daratumumab clinical trials conducted to date, as well as practical management considerations for the use of daratumumab based on our experience with the agent. © 2016 Springer International Publishing Switzerland.

Published
2016

31. Azacitidine Versus Conventional Care Regimens (CCR) in Elderly Patients (≥75 Years) with Acute Myeloid Leukemia (AML) in the AZA-AML-001 Study

Author

Seymour, J.F., primary, Buckstein, R., additional, Santini, V., additional, Döhner, H., additional, Stone, R.M., additional, Minden, M.D., additional, Kuo, C.Y., additional, Ben-Yehuda, D., additional, Bargay, J., additional, Songer, S., additional, Weaver, J., additional, Beach, C.L., additional, and Dombret, H., additional

Published
2017
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32. 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
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33. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma

Author

Stewart, Ak, Rajkumar, Sv, Dimopoulos, Ma, Masszi, T, Špička, I, Oriol, A, Hájek, R, Rosiñol, L, Siegel, Ds, Mihaylov, Gg, Goranova Marinova, V, Rajnics, P, Suvorov, A, Niesvizky, R, Jakubowiak, Aj, San Miguel JF, Ludwig, H, Wang, M, Maisnar, V, Minarik, J, Bensinger, Wi, Mateos, Mv, Ben Yehuda, D, Kukreti, V, Zojwalla, N, Tonda, Me, Yang, X, Xing, B, Moreau, P, Palumbo, A, Petrini, Mario, Aspire, Investigators, Laboratory of Molecullar and Cellular Therapy, and Clinical sciences

Subjects
Adult, Male, Oncology, medicine.medical_specialty, Kaplan-Meier Estimate, Dexamethasone, Ixazomib, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Female, Humans, Intention to Treat Analysis, Middle Aged, Multiple Myeloma, Oligopeptides, Recurrence, Thalidomide, Medicine (all), chemistry.chemical_compound, Internal medicine, 80 and over, medicine, Elotuzumab, Multiple myeloma, Lenalidomide, business.industry, General Medicine, Pomalidomide, medicine.disease, Carfilzomib, Surgery, chemistry, business, medicine.drug
Abstract

BACKGROUND: Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. METHODS: We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. RESULTS: Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P

Published
2015

34. International myeloma working group recommendations for the diagnosis and management of myeloma-related renal impairment

Author

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. S and 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. 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). Carfi

Published
2016

35. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma

Author

Avet-Loiseau, H. Fonseca, R. Siegel, D. Dimopoulos, M.A. Špička, I. Masszi, T. Hájek, R. Rosiñol, L. Goranova-Marinova, V. Mihaylov, G. Maisnar, V. Mateos, M.-V. Wang, M. Niesvizky, R. Oriol, A. Jakubowiak, A. Minarik, J. Palumbo, A. Bensinger, W. Kukreti, V. Ben-Yehuda, D. Stewart, A.K. Obreja, M. Moreau, P. and Avet-Loiseau, H. Fonseca, R. Siegel, D. Dimopoulos, M.A. Špička, I. Masszi, T. Hájek, R. Rosiñol, L. Goranova-Marinova, V. Mihaylov, G. Maisnar, V. Mateos, M.-V. Wang, M. Niesvizky, R. Oriol, A. Jakubowiak, A. Minarik, J. Palumbo, A. Bensinger, W. Kukreti, V. Ben-Yehuda, D. Stewart, A.K. Obreja, M. Moreau, P.

Abstract

The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n548; Rd, n552) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standardrisk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. Copyright © 2011 by the American Association for the Advancement of Science; all rights reserved.

Published
2016

36. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study

Author

Chanan-Khan, Asher, Cramer, Paula, Demirkan, Fatih, Fraser, Graeme, Silva, Rodrigo Santucci, Grosicki, Sebastian, Pristupa, Aleksander, Janssens, Ann, Mayer, Jiri, Bartlett, Nancy L., Dilhuydy, Marie-Sarah, Pylypenko, Halyna, Loscertales, Javier, Avigdor, Abraham, Rule, Simon, Villa, Diego, Samoilova, Olga, Panagiotidis, Panagiots, Goy, Andre, Mato, Anthony, Pavlovsky, Miguel A., Karlsson, Claes, Mahler, Michelle, Salman, Mariya, Sun, Steven, Phelps, Charles, Balasubramanian, Sriram, Howes, Angela, Hallek, Michael, Assouline, S., Bence-Bruckler, I., Buckstein, R., Fraser, G., Larratt, L., Minuk, L., Villa, D., Angevine, A., Bartlett, N., Bixby, D., Caimi, P., Chanan-Khan, A., Craig, M., Forero-Torres, A., Ganguly, S., Goy, A., Heffner, L., Hermann, R., Lansigan, F., Leis, J., Letzer, J., Link, B., Liu, D., McCaul, K., McGuire, E., Skinner, W., Starodub, A., Stuart, R., Thirman, M., Tirumali, N., Yang, J., Janssens, A., Offner, F., Van den Neste, E., Van Hoof, A., Mayer, J., Novak, J., Trneny, M., Cartron, G., Dartigeas, C., Dilhuydy, M., Ghez, D., Haioun, C., Leblond, V., Salles, G., Balser, C., Cramer, P., Dreger, P., Durig, J., Eckart, M., Heinrich, B., Illmer, T., Jentsch-Ullrich, K., Pfreundschuh, M., Schetelig, J., Schlag, R., Soling, U., Stilgenbaue, S., Anagnostopoulos, A., Dimopoulos, A., Panagiotidis, P., Vrakidou, E., Bairey, O., Ben Yehuda, D., Braester, A., Fineman, R., Herishanu, Y., Nagler, A., Ruchlemer, R., Tadmor, T., Grosicki, S., Homenda, W., Jurczak, W., Pluta, A., Woszczyk, D., Espirito Santo, A., Luis, R., Raposo, J., Viveiros, C., Alexeeva, J., Dunaev, Y., Golubeva, M., Khuageva, N., Loginov, A., Lysenko, I., Osmanov, E., Pavlov, V., Pristupa, A., Proydakov, A., Rossiev, V., Samarina, I., Samoilova, O., Serduk, O., Shneider, T., Udovitsa, D., Voloshin, S., Gayoso, J., Gonzalez, M., Gonzalez Barca, E., Hernandez Rivas, J., Jargue, I., Loscertales, J., Karlsson, C., Sender, M., Aktan, M., Arslan, O., Demirkan, F., Ferhanoglu, B., Kaynar, L., Sayinalp, N., Vaural, F., Yagci, M., Dyagil, I., Kaplan, P., Masliak, Z., Oliynyk, H., Popovska, T., Pylypenko, H., Rekhtman, G., Dearden, C., Morley, N., Moss, P., Rule, S., Pavlovsky, M., Riveros, D., Santucci-Silva, R., Romeo, M., Scheliga, A., Salazar, L., Gomez, D., Ramirez, E., Jung, C., Chanan-Khan, Asher, Cramer, Paula, Demirkan, Fatih, Fraser, Graeme, Silva, Rodrigo Santucci, Grosicki, Sebastian, Pristupa, Aleksander, Janssens, Ann, Mayer, Jiri, Bartlett, Nancy L., Dilhuydy, Marie-Sarah, Pylypenko, Halyna, Loscertales, Javier, Avigdor, Abraham, Rule, Simon, Villa, Diego, Samoilova, Olga, Panagiotidis, Panagiots, Goy, Andre, Mato, Anthony, Pavlovsky, Miguel A., Karlsson, Claes, Mahler, Michelle, Salman, Mariya, Sun, Steven, Phelps, Charles, Balasubramanian, Sriram, Howes, Angela, Hallek, Michael, Assouline, S., Bence-Bruckler, I., Buckstein, R., Fraser, G., Larratt, L., Minuk, L., Villa, D., Angevine, A., Bartlett, N., Bixby, D., Caimi, P., Chanan-Khan, A., Craig, M., Forero-Torres, A., Ganguly, S., Goy, A., Heffner, L., Hermann, R., Lansigan, F., Leis, J., Letzer, J., Link, B., Liu, D., McCaul, K., McGuire, E., Skinner, W., Starodub, A., Stuart, R., Thirman, M., Tirumali, N., Yang, J., Janssens, A., Offner, F., Van den Neste, E., Van Hoof, A., Mayer, J., Novak, J., Trneny, M., Cartron, G., Dartigeas, C., Dilhuydy, M., Ghez, D., Haioun, C., Leblond, V., Salles, G., Balser, C., Cramer, P., Dreger, P., Durig, J., Eckart, M., Heinrich, B., Illmer, T., Jentsch-Ullrich, K., Pfreundschuh, M., Schetelig, J., Schlag, R., Soling, U., Stilgenbaue, S., Anagnostopoulos, A., Dimopoulos, A., Panagiotidis, P., Vrakidou, E., Bairey, O., Ben Yehuda, D., Braester, A., Fineman, R., Herishanu, Y., Nagler, A., Ruchlemer, R., Tadmor, T., Grosicki, S., Homenda, W., Jurczak, W., Pluta, A., Woszczyk, D., Espirito Santo, A., Luis, R., Raposo, J., Viveiros, C., Alexeeva, J., Dunaev, Y., Golubeva, M., Khuageva, N., Loginov, A., Lysenko, I., Osmanov, E., Pavlov, V., Pristupa, A., Proydakov, A., Rossiev, V., Samarina, I., Samoilova, O., Serduk, O., Shneider, T., Udovitsa, D., Voloshin, S., Gayoso, J., Gonzalez, M., Gonzalez Barca, E., Hernandez Rivas, J., Jargue, I., Loscertales, J., Karlsson, C., Sender, M., Aktan, M., Arslan, O., Demirkan, F., Ferhanoglu, B., Kaynar, L., Sayinalp, N., Vaural, F., Yagci, M., Dyagil, I., Kaplan, P., Masliak, Z., Oliynyk, H., Popovska, T., Pylypenko, H., Rekhtman, G., Dearden, C., Morley, N., Moss, P., Rule, S., Pavlovsky, M., Riveros, D., Santucci-Silva, R., Romeo, M., Scheliga, A., Salazar, L., Gomez, D., Ramirez, E., and Jung, C.

Abstract

Background Most patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma relapse after initial therapy. Bendamustine plus rituximab is often used in the relapsed or refractory setting. We assessed the efficacy and safety of adding ibrutinib, an oral covalent inhibitor of Bruton's tyrosine kinase (BTK), to bendamustine plus rituximab in patients with previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma. Methods The HELIOS trial was an international, double-blind, placebo-controlled, phase 3 study in adult patients (>= 18 years of age) who had active chronic lymphocytic leukaemia or small lymphocytic lymphoma with measurable lymph node disease (>1.5 cm) by CT scan, and had relapsed or refractory disease following one or more previous lines of systemic therapy consisting of at least two cycles of a chemotherapy-containing regimen, an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate bone marrow, liver, and kidney function. Patients with del(17p) were excluded because of known poor response to bendamustine plus rituximab. Patients who had received previous treatment with ibrutinib or other BTK inhibitors, refractory disease or relapse within 24 months with a previous bendamustine-containing regimen, or haemopoietic stem-cell transplant were also excluded. Patients were randomly assigned (1:1) by a web-based system to receive bendamustine plus rituximab given in cycles of 4 weeks' duration (bendamustine: 70 mg/m.intravenously on days 2-3 in cycle 1, and days 1-2 in cycles 2-6; rituximab: 375 mg/m.on day 1 of cycle 1, and 500 mg/m.on day 1 of cycles 2-6 for a maximum of six cycles) with either ibrutinib (420 mg daily orally) or placebo until disease progression or unacceptable toxicity. Patients were stratified according to whether they were refractory to purine analogues and by number of previous lines of therapy. The primary endpoint was independent review committee (IRC)-assessed progression-fre

Published
2016

37. Associations between B-cell non-Hodgkin lymphoma and exposure, persistence and immune response to hepatitis B

Author

Kleinstern, G., primary, Seir, R. A., additional, Perlman, R., additional, Abdeen, Z., additional, Khatib, A., additional, Elyan, H., additional, Dann, E. J., additional, Kedmi, M., additional, Ellis, M., additional, Nagler, A., additional, Amir, G., additional, Ben Yehuda, D., additional, Safadi, R., additional, and Paltiel, O., additional

Published
2016
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38. Molecular Follow-Up of Disease Progression and Interferon Therapy in Chronic Myelocytic Leukemia

Author

Ben-Yehuda, D., Krichevsky, S., Rachmilewitz, E. A., Avraham, A., Palumbo, G. A., Francesco Frassoni, Sahar, D., Rosenbaum, H., Paltiel, O., Zion, M., and Ben-Neriah, Y.

Subjects
Adult, Male, Adolescent, Biochemistry, Immunology, Hematology, Cell Biology, Interferon-alpha, DNA Methylation, Genes, abl, Middle Aged, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, hemic and lymphatic diseases, Humans, Hydroxyurea, Female, Child, Promoter Regions, Genetic, Aged, Follow-Up Studies
Abstract

We previously reported that the abl promoter (Pa) undergoes de novo DNA methylation in the course of chronic myelocytic leukemia (CML). The clinical implications of this finding are the subject of the present study in which samples of CML patients, including a group treated with interferon alpha (IFNalpha) were surveyed. The methylation status of the abl promoter was monitored by polymerase chain reaction (PCR) amplification of the Pa region after digestion with several site-methylation sensitive restriction enzymes. Some 74% of the DNA samples from blood and marrow drawn in the chronic phase were nonmethylated, similar to control samples from non-CML patients. The remaining 26% were partially methylated in the abl Pa region. The latter samples were derived from patients who were indistinguishable from the others on the basis of clinical presentation. Methylated samples were mostly derived from patients known to have a disease of longer duration (26 months v 7.5 months, P = .01). Samples of 30 IFNalpha-treated patients were sequentially analyzed in the course of treatment. Fifteen patients with no evidence of Pa methylation before treatment remained methylation-free. The remainder, who displayed Pa methylation before treatment, reverted to the methylation-free status. The outcome is attributed to IFNalpha therapy, as the Pa methylation status was not reversed in any of the patients treated with hydroxyurea. Methylation of the abl promoter indicates a disease of long-standing, most likely associated with a higher probability of imminent blastic transformation. It appears to predict the outcome of IFNalpha therapy far better than the cytogenetic response.

Published
1997
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39. Risk of progression and survival in multiple myeloma relapsing after therapy with IMiDs and bortezomib

Author

Kumar, Sk, Lee, Jh, Lahuerta, Jj, Morgan, G, Richardson, Pg, Crowley, J, Haessler, J, Feather, J, Hoering, A, Moreau, P, Leleu, X, Hulin, C, Klein, Sk, Sonneveld, P, Siegel, D, Bladé, J, Goldschmidt, H, Jagannath, S, Miguel, Js, Orlowski, R, Palumbo, Antonio, Sezer, O, Rajkumar, Sv, Durie, Bg, on behalf of the International Myeloma Working Group, 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, Leif Bergsagel, P, Bird, J, Boccadoro, M, Cavo, M, Chanan Khan, A, Ming Chen, W, Child, T, Chim, J, Chng, Wj, Comenzo, R, Dalton, W, Davies, F, de Souza, C, Delforge, M, Dimopoulos, M, Dispenzieri, A, Drach, J, Drake, M, Einsele, H, Facon, T, Fantl, D, Fermand, Jp, Fonseca, R, Gahrton, G, García Sanz, R, Gasparetto, C, Gertz, M, Gibson, J, Giralt, S, Greipp, P, Hajek, R, Hardan, I, Hari, P, Harousseau, Jl, Hata, H, Hattori, Y, Heffner, T, Ho, J, Hungria, V, Ida, S, Jacobs, P, Johnsen, H, Jian, H, Joshua, D, Jurczyszyn, A, Kawano, M, Kröger, N, Kumar, S, Kyle, Ra, Lacy, M, Landgren, O, Laubach, J, Lentzsch, S, Lokhorst, H, Lonial, S, Ludwig, H, Maiolino, A, Mateos, M, Mehta, J, Mellqvist, Uh, Merlini, G, Mikhael, J, Morales, Ar, Nari, H, Munshi, N, Niesvizky, R, Nouel, A, Novis, Y, Palumbo, A, Pavlovsky, S, Pilarski, L, Powles, R, Raje, N, Vincent Rajkumar, S, Reece, D, Reiman, T, Roodman, D, Rosiñol, L, Shah, Jj, Shaughnessy, J, Shimizu, K, Shustik, C, Singhal, S, Spencer, A, Stadtmauer, E, Stewart, K, Terpos, E, Tosi, P, Tricot, G, Turesson, I, Van Camp, B, Van Ness, B, Van Riet, I, Broek, Iv, Vanderkerken, K, Vescio, R, Vesole, D, Waage, A, Wang, M, Weber, D, Westin, J, Wheatley, K, and Zonder, J.

Published
2012

40. Bortezomib plus rituximab versus rituximab alone in patients with relapsed, rituximab-naive or rituximab-sensitive, follicular lymphoma: a randomised phase 3 trial

Author

Coiffier, B, Osmanov, E, Hong, X, Scheliga, A, Mayer, J, Offner, F, Rule, S, Teixeira, A, Walewski, J, de Vos, S, Crump, M, Shpilberg, O, Esseltine, D, Zhu, E, Enny, C, Theocharous, P, van de Velde, H, Elsayed, Y, Zinzani, P, Abdulkadyrov, K, Afanasiev, B, Aguayo Gonzalez, A, Andre, M, Belada, D, Ben Yehuda, D, Bezares, R, Biakhov, M, Bolam, S, Borbenyi, Z, Bron, D, Buckstein, R, Bumbea, H, Caballero Barrigon, M, Campos, L, Cantonetti, M, Capra Zanella, M, Christiansen, N, Cohen, G, Colita, N, Cosgriff, T, Culligan, D, Del Giglio, A, Dichmann, R, Dietzfelbinger, H, Digumarti, R, Dmoszynska, A, Domnikova, N, Dubinsky, P, Dunaev, Y, Easow, J, Eberwine, S, Economopoulos, T, Egyed, M, Ellerton, J, Eom, H, Farmer, L, Fenske, T, Fields, P, Fillet, G, Frank, R, Gaisarova, G, Garicochea, B, Gasztonyi, Z, Gavish, I, Gheorghita, E, Gladkov, O, Goldberg, V, Golenkov, A, Gomez Almaguer, D, Gonzalez Barca, E, Guan, Z, Gupta, S, Hellmann, A, Hermann, R, Honkanen, T, Hu, E, Huang, X, Hudecek, J, Illes, A, Intragumtornchai, T, Jedrzejczak, W, Jones, L, Jootar, S, Kahanic, S, Karamanesht, E, Ke, X, Khuageva, N, Kim, W, Kimby, E, Komisarenko, V, Kouroukis, T, Kuliczkowski, K, Kuzina, L, Kyselyova, M, Labanca, V, Lange, A, Le Gouill, S, Leahy, M, Liberati, A, Linden, O, Liu, T, Lubennikov, V, Lundin, J, Lysa, T, Lysenko, I, Lytvyn, I, Makhson, A, Manikhas, G, Masliak, Z, Mcintyre, R, Medvedeva, N, Mena, R, Merkulov, V, Mesters, R, Milpied, N, Min, Y, Moezi, M, Mohrbacher, A, Mollee, P, Morgan, D, Morschhauser, F, Mysanikov, A, Nagler, A, Nair, S, Naparstek, E, Nawarawong, W, Noga, S, Oliveira, I, Okada, C, Oriol Rocafiguera, A, Page, R, Papajik, T, Pasquini, R, Patel, M, Patel, R, Paton, E, Pavlov, V, Pospelova, T, Prasad, S, Pylypenko, H, Raposo, J, Rekhtman, G, Rivas, S, Robak, T, Saba, S, Salles, G, Saltzman, M, Samoilova, O, Samuels, B, Sanani, S, Sebban, C, Silva da Gomes, M, Shen, Z, Shi, Y, Shtalrid, M, Siritanaratkul, N, Skotnicki, A, Solal Celigny, P, Soubeyran, P, Spencer, A, Stevens, D, Suh, C, Sulek, K, Suvorov, A, Szer, J, Theunissen, K, To Bik, L, Tothova, E, Trneny, M, Van De Velde, A, Van Hoof, A, Van Steenweghen, S, Vanhatalo, S, Varma, S, Vidyasagar, M, Vilchevskaya, K, Vitolo, U, Wang, H, Warzocha, K, Wild, A, Zachee, P, Zanichelli, M, Zhang, W, Zoppegno, L, Zoumbos, N, Coiffier B., Osmanov E.A., Hong X., Scheliga A., Mayer J., Offner F., Rule S., Teixeira A., Walewski J., de Vos S., Crump M., Shpilberg O., Esseltine D.L., Zhu E., Enny C., Theocharous P., van de Velde H., Elsayed Y.A., Zinzani P.L., and LYM-3001 study investigators

Subjects
Oncology, Male, Lymphoma, Settore MED/06 - Oncologia Medica, Follicular lymphoma, Bortezomib, Antibodies, Monoclonal, Murine-Derived, 0302 clinical medicine, Maintenance therapy, Prednisone, immune system diseases, Recurrence, hemic and lymphatic diseases, Monoclonal, Antineoplastic Combined Chemotherapy Protocols, 80 and over, Lymphoma, Follicular, Multiple myeloma, Infusion Pumps, Aged, 80 and over, Middle Aged, Boronic Acids, 3. Good health, 030220 oncology & carcinogenesis, Pyrazines, Rituximab, Female, medicine.drug, Murine-Derived, Adult, medicine.medical_specialty, rituximab-naive, Antineoplastic Agents, Antibodies, Disease-Free Survival, 03 medical and health sciences, Young Adult, follicular lymphoma, Internal medicine, Neoplasm Staging, Humans, Aged, medicine, business.industry, Follicular, medicine.disease, Clinical trial, rituximab-sensitive, Immunology, business, Settore MED/15 - Malattie del Sangue, 030215 immunology
Abstract

BACKGROUND: Bortezomib and rituximab have shown additive activity in preclinical models of lymphoma, and have been shown to be active and generally well tolerated in a randomised phase 2 study in patients with follicular and marginal zone lymphoma. We compared the efficacy and safety of rituximab alone or combined with bortezomib in patients with relapsed or refractory follicular lymphoma in a phase 3 setting. METHODS: In this multicentre phase 3 trial, rituximab-naive or rituximab-sensitive patients aged 18 years or older with relapsed grade 1 or 2 follicular lymphoma were randomly assigned (1:1) to receive five 35-day cycles consisting of intravenous infusions of rituximab 375 mg/m(2) on days 1, 8, 15, and 22 of cycle 1, and on day 1 of cycles 2-5, either alone or with bortezomib 1·6 mg/m(2), administered by intravenous injection on days 1, 8, 15, and 22 of all cycles. Randomisation was stratified by FLIPI score, previous use of rituximab, time since last therapy, and region. Treatment assignment was based on a computer-generated randomisation schedule prepared by the sponsor. Patients and treating physicians were not masked to treatment allocation. The primary endpoint was progression-free survival analysed by intention to treat. This trial has been completed and is registered with ClinicalTrials.gov, number NCT00312845. FINDINGS: Between April 10, 2006, and Aug 12, 2008, 676 patients were randomised to receive rituximab (n=340) or bortezomib plus rituximab (n=336). After a median follow-up of 33·9 months (IQR 26·4-39·7), median progression-free survival was 11·0 months (95% CI 9·1-12·0) in the rituximab group and 12·8 months (11·5-15·0) in the bortezomib plus rituximab group (hazard ratio 0·82, 95% CI 0·68-0·99; p=0·039). The magnitude of clinical benefit was not as large as the anticipated prespecified improvement of 33% in progression-free survival. Patients in both groups received a median of five treatment cycles (range 1-5); 245 of 339 (72%) and 237 of 334 (71%) patients in the rituximab and bortezomib plus rituximab groups, respectively, completed five cycles. Of patients who did not complete five cycles, most discontinued early because of disease progression (77 [23%] patients in the rituximab group, and 56 [17%] patients in the bortezomib plus rituximab group). Rates of adverse events of grade 3 or higher (70 [21%] of 339 rituximab-treated patients vs 152 [46%] of 334 bortezomib plus rituximab treated patients), and serious adverse events (37 [11%] patients vs 59 [18%] patients) were lower in the rituximab group than in the combination group. The most common adverse events of grade 3 or higher were neutropenia (15 [4%] patients in the rituximab group and 37 [11%] patients in the bortezomib plus rituximab group), infection (15 [4%] patients and 36 [11%] patients, respectively), diarrhoea (no patients and 25 [7%] patients, respectively), herpes zoster (one [

Published
2011

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

Author

Kumar, Sk, Lee, Jh, Lahuerta, Jj, Morgan, G, Richardson, Pg, Crowley, J, Haessler, J, Feather, J, Hoering, A, Moreau, P, Leleu, X, Hulin, C, Klein, Sk, Sonneveld, P, Siegel, D, Bladé, J, Goldschmidt, H, Jagannath, S, Miguel, Js, Orlowski, R, Palumbo, Antonio, Sezer, O, Rajkumar, Sv, Durie, Bg, on behalf of the International Myeloma Working Group, 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, Leif Bergsagel, P, Bird, J, Boccadoro, M, Cavo, M, Chanan Khan, A, Ming Chen, W, Child, T, Chim, J, Chng, Wj, Comenzo, R, Dalton, W, Davies, F, de Souza, C, Delforge, M, Dimopoulos, M, Dispenzieri, A, Drach, J, Drake, M, Einsele, H, Facon, T, Fantl, D, Fermand, Jp, Fonseca, R, Gahrton, G, García Sanz, R, Gasparetto, C, Gertz, M, Gibson, J, Giralt, S, Greipp, P, Hajek, R, Hardan, I, Hari, P, Harousseau, Jl, Hata, H, Hattori, Y, Heffner, T, Ho, J, Hungria, V, Ida, S, Jacobs, P, Johnsen, H, Jian, H, Joshua, D, Jurczyszyn, A, Kawano, M, Kröger, N, Kumar, S, Kyle, Ra, Lacy, M, Landgren, O, Laubach, J, Lentzsch, S, Lokhorst, H, Lonial, S, Ludwig, H, Maiolino, A, Mateos, M, Mehta, J, Mellqvist, Uh, Merlini, G, Mikhael, J, Morales, Ar, Nari, H, Munshi, N, Niesvizky, R, Nouel, A, Novis, Y, Palumbo, A, Pavlovsky, S, Pilarski, L, Powles, R, Raje, N, Vincent Rajkumar, S, Reece, D, Reiman, T, Roodman, D, Rosiñol, L, Shah, Jj, Shaughnessy, J, Shimizu, K, Shustik, C, Singhal, S, Spencer, A, Stadtmauer, E, Stewart, K, Terpos, E, Tosi, P, Tricot, G, Turesson, I, Van Camp, B, Van Ness, B, Van Riet, I, Broek, Iv, Vanderkerken, K, Vescio, R, Vesole, D, Waage, A, Wang, M, Weber, D, Westin, J, Wheatley, K, and Zonder, J.

Published
2011

43. MELPHALAN/PREDNISONE/LENALIDOMIDE (MPR) VERSUS HIGHDOSEMELPHALAN AND AUTOLOGOUS TRANSPLANTATION (MEL200)IN NEWLY DIAGNOSED MULTIPLE MYELOMA (MM) PATIENTS: APHASE III STUDY

Author

Palumbo, Antonio, Cavallo, Federica, Lupo, B., Nagler, A., Redoglia, V., Cavalli, M., Carella, A., Cafro, A., Patriarca, F., Siniscalchi, A., Rossini, F., Crippa, C., Corradini, P., Cavo, M., Grammatico, S., Stanevsky, A., Ben Yehuda, D., Di Raimondo, F., Caravita Di Toritto, T., and Boccadoro, Mario

Published
2011

47. Editorial

Author

Aby Lewin, Dror Meirow, Poliack A, Ben Yehuda D, E Rachmilewitz, J.G. Schenker, and Prus D

Subjects
Hodgkin s, medicine.medical_specialty, Pathology, business.industry, Ovarian tissue, General surgery, Reproductive medicine, Obstetrics and Gynecology, Disease, University hospital, humanities, Reproductive Medicine, Obstetrics and gynaecology, medicine, In patient, business
Abstract

Received August 15, 1997; revised and accepted January 2, 1998. Reprint requests: Dror Meirow, Department of Obstetrics and Gynecology, Hadassah University Hospital, P.O. Box 12000, Jerusalem, Israel (FAX: 00972-26434434). * Department of Obstetrics and Gynecology. 1 Department of Hematology. Department of Pathology. The opinions and commentary expressed in Editor's Corner articles are solely those of the author. Its publication does not imply endorsement by the Editor or American Society for Reproductive Medicine.

Published
1998
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48. International Myeloma Working Group recommendations for global myeloma care

Author

Ludwig, H. Miguel, J.S. Dimopoulos, M.A. Palumbo, A. Garcia Sanz, R. Powles, R. Lentzsch, S. Ming Chen, W. Hou, J. Jurczyszyn, A. Romeril, K. Hajek, R. Terpos, E. Shimizu, K. Joshua, D. Hungria, V. Rodriguez Morales, A. Ben-Yehuda, D. Sondergeld, P. Zamagni, E. Durie, B. and Ludwig, H. Miguel, J.S. Dimopoulos, M.A. Palumbo, A. Garcia Sanz, R. Powles, R. Lentzsch, S. Ming Chen, W. Hou, J. Jurczyszyn, A. Romeril, K. Hajek, R. Terpos, E. Shimizu, K. Joshua, D. Hungria, V. Rodriguez Morales, A. Ben-Yehuda, D. Sondergeld, P. Zamagni, E. Durie, B.

Abstract

Recent developments have led to remarkable improvements in the assessment and treatment of patients with multiple myeloma (MM). New technologies have become available to precisely evaluate the biology and extent of the disease, including information about cytogenetics and genetic abnormalities, extramedullary manifestations and minimal residual disease. New, more effective drugs have been introduced into clinical practice, which enable clinicians to significantly improve the outcome of patients but also pose new challenges for the prevention and management of their specific side effects. Given these various new options and challenges, it is important to identify the minimal requirements for diagnosis and treatment of patients, as access to the most sophisticated advances may vary depending on local circumstances. Here, we propose the minimal requirements and possible options for diagnosis, monitoring and treatment of patients with multiple myeloma. © 2014 Macmillan Publishers Limited. All rights reserved.

Published
2014

49. Immune regulatory effects of panobinostat in patients with Hodgkin lymphoma through modulation of serum cytokine levels and T-cell PD1 expression

Author

Oki, Y., Buglio, D., Zhang, J., Ying, Y., Zhou, S., Sureda, A., Ben-Yehuda, D., Zinzani, P. L., Prince, H. M., Harrison, S. J., Kirschbaum, M., Johnston, P. B., Shen, A., von Tresckow, B., Younes, A., Oki, Y., Buglio, D., Zhang, J., Ying, Y., Zhou, S., Sureda, A., Ben-Yehuda, D., Zinzani, P. L., Prince, H. M., Harrison, S. J., Kirschbaum, M., Johnston, P. B., Shen, A., von Tresckow, B., and Younes, A.

Published
2014

50. Immune regulatory effects of panobinostat in patients with Hodgkin lymphoma through modulation of serum cytokine levels and T-cell PD1 expression

Author

Oki, Y, Buglio, D, Zhang, J, Ying, Y, Zhou, S, Sureda, A, Ben-Yehuda, D, Zinzani, PL, Prince, HM, Harrison, SJ, Kirschbaum, M, Johnston, PB, Shen, A, von Tresckow, B, Younes, A, Oki, Y, Buglio, D, Zhang, J, Ying, Y, Zhou, S, Sureda, A, Ben-Yehuda, D, Zinzani, PL, Prince, HM, Harrison, SJ, Kirschbaum, M, Johnston, PB, Shen, A, von Tresckow, B, and Younes, A

Published
2014

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