35 results on '"Falcone AP"'
Search Results
2. P17: DARATUMUMAB (D) PLUS LENALIDOMIDE (R) AND DEXAMETHASONE (D) AS SALVAGE THERAPY FOR PATIENTS WITH REFRACTORY-RELAPSED MULTIPLE MYELOMA (RRMM): INITIAL FOLLOW-UP OF AN ITALIAN MULTICENTER RETROSPECTIVE CLINICAL EXPERIENCE BY “RETE EMATOLOGICA PUGLIESE”
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Mele, G, primary, Cascavilla, N, additional, Di Renzo, N, additional, Guarini, A, additional, Mazza, P, additional, Melillo, L, additional, Pavone, V, additional, Tarantini, G, additional, Curci, P, additional, Falcone, AP, additional, Germano, C, additional, Mele, A, additional, Palazzo, G, additional, Palumbo, G, additional, Reddiconto, G, additional, Rossini, B, additional, Specchia, G, additional, Musto, P, additional, and Pastore, D, additional
- Published
- 2022
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3. SUBCUTANEOUS VELCADE PLUS PREDNISONE (VP) OR PLUS CYCLOPHOSFAMIDE (VCP) OR PLUS MELPHALAN (VMP) IN FRAIL, ELDERLY, NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS: A PHASE II COMMUNITY–BASED STUDY
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Larocca, A, Oliva, S, Offidani, M, Levi, A, Musolino, Caterina, Falcone, Ap, Conticello, C, Caravita, T, Rossi, D, Villani, O, Nozzoli, C, Benevolo, G, Liberati, Am, Morabito F, Derudas D., Carella, Am, Caraffa, P, Astolfi, M, Palladino, C, Montefusco, V, Cavallo, F, Petrucci, Mt, Boccadoro, M, Sonneveld, P, and Palumbo, A.
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subcutaneous bortezomib ,Multiple Myeloma, subcutaneous bortezomib ,Multiple Myeloma - Published
- 2013
4. Efficacy and safety of 3 lenalidomide–based combinations in elderly newly diagnosed multiple myeloma patients: results from the phase 3 community based EMN01 trial
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Gay, F, Bringhen, S, Offidani, M, Liberati, Am, Cellini, C, Magarotto, V, Benevolo, G, Aitoro, G, Patriarca, F, Omede, P, Conticello, C, Montefusco, V, Rossi, D, Palladino, C, Pour, L, Allegra, Alessandro, Pietrantuono, G, Falcone, Ap, Rocci, A, Zambello, R, Ledda, A, Gentili, S, Musto, P, Boccadoro, M, Hajek, R, and Palumbo, A.
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Multiple myeloma, Lenalidomide, EMN01 ,EMN01 ,Multiple myeloma ,Lenalidomide - Published
- 2013
5. Melphalan/Prednisone/Lenalidomide (MPR) Versus High-Dose Melphalan and Autologous Transplantation (MEL200) in Newly Diagnosed Multiple Myeloma (MM) Patients <65 Years: Results of a Randomized Phase III Study
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Palumbo, Antonio, Cavallo, Federica, Hardan, I, Lupo, B, Redoglia, V, Levin, M, Corradini, P, Pezzatti, S, Patriarca, F, Cavo, M, Marcatti, M, Pescosta, N, Falcone, Ap, Ria, R, Rossi, D, Benevolo, G, Cangialosi, C, Galli, M, Catalano, L, Baraldi, A, Carella, Am, Cafro, A, Siniscalchi, A, Crippa, C, Grammatico, S, Cavalli, M, Caravita Di Toritto, T, Di Raimondo, F, Nagler, A, and Boccadoro, Mario
- Published
- 2011
6. Melphalan 200 mg/m2 versus Melphalan 100 mg/m2 in newly diagnosed myeloma patients: a prospective, multi-center phase III study
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Palumbo, A, Bringhen, S, Bruno, B, Falcone, Ap, Liberati, Am, Grasso, M, Ria, R, Pisani, F, Cangialosi, C, Caravita, T, Levi, A, Meloni, Giovanna, Nozza, A, Pregno, P, Gabbas, A, Callea, V, Rizzo, M, Annino, L, DE STEFANO, V, Musto, P, Baldi, I, Cavallo, F, Petrucci, Mt, Massaia, M, and Boccadoro, M.
- Published
- 2010
7. A426 Bortezomib or Lenalidomide to Treat Disease Relapse After Allogeneic Transplantation in Myeloma
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Montefusco, V Falcone, AP Carella, AM Olivieri, A Sanpaolo, G Farina, L Spina, F Dodero, A Morelli, M Milani, R others
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Health Sciences ,Επιστήμες Υγείας - Published
- 2009
8. A092 RMPT in Relapsed/Refractory Multiple Myeloma: Results of a Multicenter Phase II Clinical Trial
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Palumbo, A, primary, Larocca, A, additional, Sanpaolo, G, additional, Falcone, AP, additional, Federico, V, additional, Canepa, L, additional, Crugnola, M, additional, Baldini, L, additional, Magarotto, V, additional, Falco, P, additional, Petrucci, MT, additional, and Boccadoro, M, additional
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- 2009
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9. A426 Bortezomib or Lenalidomide to Treat Disease Relapse After Allogeneic Transplantation in Myeloma
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Montefusco, V, primary, Falcone, AP, additional, Carella, AM, additional, Olivieri, A, additional, Sanpaolo, G, additional, Farina, L, additional, Spina, F, additional, Dodero, A, additional, Morelli, M, additional, Milani, R, additional, Cascavilla, N, additional, and Corradini, P, additional
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- 2009
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10. Alterazioni immunologiche negli emofilici. Studio di una casistica modenese
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Sacchi, Stefano, Luppi, G, Falcone, Ap, Piccinini, Lino, Marietta, M, Rinaldi, G, Roncaglia, R, Barbieri, U, Di Prisco AU, and Torelli, U.
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nd - Published
- 1986
11. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients
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Sara Bringhen, Giulia Benevolo, Anna Marina Liberati, Vincenzo Callea, Mariella Genuardi, Antonietta Falcone, Alessandra Larocca, Mario Boccadoro, Luca De Rosa, Mariella Grasso, Francesca Patriarca, Clotilde Cangialosi, Tommasina Guglielmelli, Maide Cavalli, Gianluca Gaidano, Pellegrino Musto, Chiara Nozzoli, Michele Cavo, Antonio Palumbo, Roberto Ria, Davide Rossi, Silvia Gentili, Vincenzo Rizzo, Andrea Evangelista, Anna Levi, Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, and Palumbo A.
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Male ,Kaplan-Meier Estimate ,Settore MED/03 - GENETICA MEDICA ,Biochemistry ,law.invention ,Bortezomib ,PROTEASOME INHIBITOR ,Randomized controlled trial ,law ,Antineoplastic Combined Chemotherapy Protocols ,ELDERLY-PATIENTS ,Melphalan ,Multiple myeloma ,LENALIDOMIDE ,INDUCTION ,Incidence ,Peripheral Nervous System Diseases ,Hematology ,RANDOMIZED CONTROLLED-TRIAL ,Middle Aged ,Boronic Acids ,Thalidomide ,PREDNISONE PLUS THALIDOMIDE ,Treatment Outcome ,OF-THE-LITERATURE ,Pyrazines ,Female ,Multiple Myeloma ,medicine.drug ,medicine.medical_specialty ,Immunology ,Disease-Free Survival ,Drug Administration Schedule ,Internal medicine ,medicine ,Humans ,ORAL MELPHALAN ,Adverse effect ,Survival rate ,Lenalidomide ,Aged ,Neoplasm Staging ,Intention-to-treat analysis ,business.industry ,PERIPHERAL NEUROPATHY ,PHASE-III ,Cell Biology ,medicine.disease ,Surgery ,Peripheral neuropathy ,Prednisone ,business - Abstract
In a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179.
- Published
- 2010
12. Clinical Efficacy of Isatuximab Plus Carfilzomib and Dexamethasone in Relapsed/Refractory Multiple Myeloma Patients.
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De Novellis D, Derudas D, Vincelli D, Fontana R, Della Pepa R, Palmieri S, Accardi F, Rotondo F, Morelli E, Gigliotta E, Roccotelli D, Marano L, Barone ML, Cetani G, Esposito D, Lazzaro A, Delle Cave G, Serio B, Morini D, Porrazzo M, Urciuoli E, Masucci C, Fanelli F, Rizzo M, Arcamone M, Trastulli F, Rocco S, Leone A, Bianco R, Salvatore F, Idato A, Sicari M, Tosi P, Rascato MG, Di Perna M, Falcone AP, Morello L, Carlisi M, Svanera G, Annunziata M, Frigeri F, Califano C, Carella AM, Marcacci G, Pane F, Risitano AM, Giudice V, Botta C, and Selleri C
- Abstract
Isatuximab, a novel anti-CD38 monoclonal antibody, is approved in combination with carfilzomib and dexamethasone (Isa-Kd) in relapsed/refractory multiple myeloma (RRMM) patients. Because of its recent introduction, real-world efficacy and safety are poorly reported. In this Italian multicenter real-life observational retrospective study, efficacy and safety of the Isa-Kd regimen were evaluated in a cohort of 103 RRMM patients. Overall response rate (ORR) was 85%, with stringent (sCR) or complete response (CR) in 18% of cases and very good partial response (VGPR) in 39%. Median PFS and OS were not reached within the study period, while 1-year PFS and OS were 72% and 77%, respectively. Hematological toxicities were observed in 42% of subjects, and cardiac toxicities occurred in 24% of cases. Moreover, we conducted a subanalysis on patients (N = 69) treated with Isa-Kd after one prior line of therapy, showing an ORR of 88%, with sCR + CR in 20% of subjects, VGPR in 46%, and PR in 22% of patients. In this group, median PFS and OS were not reached, while 1-year PFS and OS were 92% and 95%, respectively. In conclusions, our study confirmed Isa-Kd as an effective treatment option for RRMM with a manageable safety profile even in real-life settings., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)
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- 2024
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13. Real-world evidence on the use of daratumumab, bortezomib and dexamethasone (DVd) in lenalidomide-refractory myeloma patients: subgroup analysis of the multicenter retrospective experience by "rete ematologica pugliese".
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Mele G, Di Renzo N, Cascavilla N, Carella AM, Guarini A, Mazza P, Melillo L, Pavone V, Tarantini G, Curci P, Falcone AP, Germano C, Mele A, Merchionne F, Palazzo G, Palumbo G, Quinto AM, Reddiconto G, Rossini B, Spina A, Sgherza N, Specchia G, Musto P, and Pastore D
- Subjects
- Humans, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bortezomib therapeutic use, Dexamethasone therapeutic use, Lenalidomide therapeutic use, Retrospective Studies, Multicenter Studies as Topic, Antibodies, Monoclonal, Multiple Myeloma drug therapy, Neoplasms, Plasma Cell
- Published
- 2023
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14. Carfilzomib combined with lenalidomide and dexamethasone (KRd) as salvage therapy for multiple myeloma patients: italian, multicenter, retrospective clinical experience with 600 cases outside of controlled clinical trials.
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Martino EA, Conticello C, Zamagni E, Pavone V, Palmieri S, Musso M, Tacchetti P, Mele A, Catalano L, Vigna E, Bruzzese A, Mendicino F, Botta C, Vincelli ID, Farina G, Barone M, Cangialosi C, Mancuso K, Rizziello I, Rocchi S, Falcone AP, Mele G, Reddiconto G, Garibaldi B, Iaccino E, Tripepi G, Gamberi B, Di Raimondo F, Musto P, Neri A, Cavo M, Morabito F, and Gentile M
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- Humans, Lenalidomide, Salvage Therapy, Retrospective Studies, Dexamethasone adverse effects, Multiple Myeloma drug therapy
- Abstract
In combination with lenalidomide and dexamethasone (KRd), Carfilzomib has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) on ASPIRE trial. Efficacy and safety of the triplet are still the object of investigation by many groups to confirm ASPIRE results in the setting of RRMM treated in real-life who don't meet trial restrictive inclusion criteria. Therefore, we report a retrospective multicenter analysis of 600 RRMM patients treated with KRd between December 2015 and December 2018. The median age was 64 years (range 33-85), and the median number of previous therapies was two (range 1-11). After a median of 11 KRd cycles, the overall response rate was 79.9%. The median progression-free survival (PFS) was 22 months, and the 2-year probability of PFS was 47.6%. Creatinine clearance<30 ml/min, >1 line of previous therapy, and high-risk FISH were all associated with a poor prognosis in multivariate analysis. The median overall survival (OS) was 34.8 months; the 2-year probability of OS was 63.5%. At multivariate analysis, creatinine clearance<30 ml/min, >1 line of previous therapy, and high-risk FISH were significantly associated with poor prognosis. After a median follow-up of 16 months (range 1-50), 259 withdrew from therapy. The main discontinuation reason was progressive disease (81.8%). Seventy-four patients (12.3%) discontinued therapy for toxicity. The most frequent side effects were hematological (anemia 49.3%, neutropenia 42.7%, thrombocytopenia 42.5%) and cardiovascular (hypertension 14.5%, heart failure 2.5%, arrhythmias 3.6%). Our study confirms the safety and efficacy of KRd in the real-life setting of RRMM patients and encourages its use in clinical practice., (© 2022 John Wiley & Sons Ltd.)
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- 2022
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15. Daratumumab plus bortezomib or daratumumab plus lenalidomide as salvage therapy for patients with myeloma: initial follow-up of an Italian multicentre retrospective clinical experience by 'Rete Ematologica Pugliese'.
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Mele G, Cascavilla N, Di Renzo N, Guarini A, Mazza P, Melillo L, Pavone V, Tarantini G, Curci P, Falcone AP, Germano C, Mele A, Palazzo G, Palumbo G, Reddiconto G, Rossini B, Specchia G, Musto P, and Pastore D
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- Antibodies, Monoclonal, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bortezomib, Dexamethasone, Follow-Up Studies, Humans, Lenalidomide, Retrospective Studies, Salvage Therapy, Multiple Myeloma drug therapy, Neoplasms, Plasma Cell
- Abstract
We report herein a multicentre retrospective analysis of 192 consecutive patients with symptomatic refractory/relapsed multiple myeloma (RRMM) treated with daratumumab in combination with bortezomib or lenalidomide as salvage therapy at 9 haematological centres in Puglia. Choice of both regimens was based on previous treatment and/or physicians' preference. Considering the under-representation of older patients (very old patient ≥ 80 years) in clinical trials and the prognostic and predictive importance and value of frailty status, here, we further characterised the patient cohort by age. The overall response rate (ORR) was generally lower than what was previously reported in the CASTOR (ORR 72.6% vs 85%) and POLLUX (ORR 86.5% vs 93%) trials. The lower ORR in our analysis compared to the CASTOR and POLLUX trials could be related to a less selected population. Similarly, amongst very old patients, the ORR was encouraging: ORR to treatment with DVd (daratumumab + bortezomib + dexamethasone) was 66.7%, and ORR to treatment with DRd (daratumumab + lenalidomide + dexamethasone) was 92.3%. Median TTP (time to progression) was 10.8 months (1-year TTP: 44.7%; 2-year TTP: 25.3%) in the DVd group; median TTP was not reached in the DRd group (1-year TTP: 82.7%; 2-year TTP: 71.4%). Median OS (overall survival) was not reached either in the DRd group (1-year OS: 85.9%; 2-year OS: 73.7%) or the DVd group (1-year OS: 70.2%; 2-year OS: 58.9%)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
- Published
- 2022
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16. Survival Risk Scores for Real-Life Relapsed/Refractory Multiple Myeloma Patients Receiving Elotuzumab or Carfilzomib In Combination With Lenalidomide and Dexamethasone as Salvage Therapy: Analysis of 919 Cases Outside Clinical Trials.
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Morabito F, Zamagni E, Conticello C, Pavone V, Palmieri S, Bringhen S, Galli M, Mangiacavalli S, Derudas D, Rossi E, Ria R, Catalano L, Tacchetti P, Mele G, Vincelli ID, Martino EA, Vigna E, Bruzzese A, Mendicino F, Botta C, Mele A, Pantani L, Rocchi S, Garibaldi B, Cascavilla N, Ballanti S, Tripepi G, Frigeri F, Falcone AP, Cangialosi C, Reddiconto G, Farina G, Barone M, Rizzello I, Iaccino E, Mimmi S, Curci P, Gamberi B, Musto P, De Stefano V, Musso M, Petrucci MT, Offidani M, Di Raimondo F, Boccadoro M, Cavo M, Neri A, and Gentile M
- Abstract
The present study aimed to develop two survival risk scores (RS) for overall survival (OS, SRS
KRd/EloRd ) and progression-free survival (PFS, PRSKRd/EloRd ) in 919 relapsed/refractory multiple myeloma (RRMM) patients who received carfilzomib, lenalidomide, and dexamethasone (KRd)/elotuzumab, lenalidomide, and dexamethasone (EloRd). The median OS was 35.4 months, with no significant difference between the KRd arm versus the EloRd arm. In the multivariate analysis, advanced ISS (HR = 1.31; P = 0.025), interval diagnosis-therapy (HR = 1.46; P = 0.001), number of previous lines of therapies (HR = 1.96; P < 0.0001), older age (HR = 1.72; P < 0.0001), and prior lenalidomide exposure (HR = 1.30; P = 0.026) remained independently associated with death. The median PFS was 20.3 months, with no difference between the two strategies. The multivariate model identified a significant progression/death risk increase for ISS III (HR = 1.37; P = 0.002), >3 previous lines of therapies (HR = 1.67; P < 0.0001), older age (HR = 1.64; P < 0.0001), and prior lenalidomide exposure (HR = 1.35; P = 0.003). Three risk SRSKRd/EloRd categories were generated: low-risk (134 cases, 16.5%), intermediate-risk (467 cases, 57.3%), and high-risk categories (213 cases, 26.2%). The 1- and 2-year OS probability rates were 92.3% and 83.8% for the low-risk (HR = 1, reference category), 81.1% and 60.6% (HR = 2.73; P < 0.0001) for the intermediate-risk, and 65.5% and 42.5% (HR = 4.91; P < 0.0001) for the high-risk groups, respectively. Notably, unlike the low-risk group, which did not cross the median timeline, the OS median values were 36.6 and 18.6 months for the intermediate- and high-risk cases, respectively. Similarly, three PRSKRd/EloRd risk categories were engendered. Based on such grouping, 338 (41.5%) cases were allocated in the low-, 248 (30.5%) in the intermediate-, and 228 (28.0%) in the high-risk groups. The 1- and 2-year PFS probability rates were 71.4% and 54.5% for the low-risk (HR = 1, reference category), 68.9% and 43.7% (HR = 1.95; P < 0.0001) for the intermediate-risk, and 48.0% and 27.1% (HR = 3.73; P < 0.0001) for the high-risk groups, respectively. The PFS median values were 29.0, 21.0, and 11.7 months for the low-, intermediate-, and high-risk cases. This analysis showed 2.7- and 4.9-fold increased risk of death for the intermediate- and high-risk cases treated with KRd/EloRd as salvage therapy. The combined progression/death risks of the two categories were increased 1.3- and 2.2-fold compared to the low-risk group. In conclusion, SRSKRd/EloRd and PRSKRd/EloRd may represent accessible and globally applicable models in daily clinical practice and ultimately represent a prognostic tool for RRMM patients who received KRd or EloRd., Competing Interests: PT received honoraria from Bristol-Myers Squibb, Takeda, Janssen, Celgene, Amgen; LP received honoraria from Celgene, Takeda, Janssen, Amgen; EZ has received a speaker honorarium from Bristol-Myers Squibb, Takeda, Janssen, Celgene, Amgen; MC has received a speaker honorarium from Adaptive Biotechnology, Amgen, Bristol-Myers Squibb, Celgene, Janssen, Takeda, AbbVie, GlaxoSmithKline and he is a member of committee of these Company; CC and FDR received honoraria from Amgen. CC, and FDR received honoraria from Celgene. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morabito, Zamagni, Conticello, Pavone, Palmieri, Bringhen, Galli, Mangiacavalli, Derudas, Rossi, Ria, Catalano, Tacchetti, Mele, Vincelli, Martino, Vigna, Bruzzese, Mendicino, Botta, Mele, Pantani, Rocchi, Garibaldi, Cascavilla, Ballanti, Tripepi, Frigeri, Falcone, Cangialosi, Reddiconto, Farina, Barone, Rizzello, Iaccino, Mimmi, Curci, Gamberi, Musto, De Stefano, Musso, Petrucci, Offidani, Di Raimondo, Boccadoro, Cavo, Neri and Gentile.)- Published
- 2022
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17. Ixazomib-based induction regimens plus ixazomib maintenance in transplant-ineligible, newly diagnosed multiple myeloma: the phase II, multi-arm, randomized UNITO-EMN10 trial.
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Mina R, Falcone AP, Bringhen S, Liberati AM, Pescosta N, Petrucci MT, Ciccone G, Capra A, Patriarca F, Rota-Scalabrini D, Bonello F, Musolino C, Cea M, Zambello R, Tacchetti P, Belotti A, Cellini C, Paris L, Grasso M, Aquino S, De Paoli L, De Sabbata G, Ballanti S, Offidani M, Boccadoro M, Monaco F, Corradini P, and Larocca A
- Subjects
- Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Boron Compounds adverse effects, Female, Glycine adverse effects, Glycine therapeutic use, Humans, Induction Chemotherapy, Maintenance Chemotherapy, Male, Middle Aged, Treatment Outcome, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Boron Compounds therapeutic use, Glycine analogs & derivatives, Multiple Myeloma drug therapy
- Published
- 2021
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18. Carfilzomib, lenalidomide, and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience of Rete Ematologica Pugliese (REP).
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Mele A, Prete E, De Risi C, Citiso S, Greco G, Falcone AP, Sanpaolo G, Mele G, Giannotta A, Vergine C, Reddiconto G, Palazzo G, Sabatelli S, Germano C, Miccolis R, Curci P, Palumbo G, Offidani M, Rizzi R, Cascavilla N, Pastore D, Di Renzo N, Mazza P, Tarantini G, Guarini A, Capalbo S, Specchia G, Greco A, De Francesco R, Sibilla S, Tonialini L, Morciano MR, and Pavone V
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Dexamethasone administration & dosage, Dexamethasone adverse effects, Disease-Free Survival, Female, Humans, Lenalidomide administration & dosage, Lenalidomide adverse effects, Male, Middle Aged, Oligopeptides administration & dosage, Oligopeptides adverse effects, Recurrence, Survival Rate, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Multiple Myeloma drug therapy, Multiple Myeloma mortality
- Abstract
Carfilzomib, lenalidomide, and dexamethasone (KRd) have been approved for the treatment of relapsed and refractory multiple myeloma (RRMM) based on ASPIRE clinical trial. However, its effectiveness and safety profile in real clinical practice should be further assessed. We retrospectively evaluated 130 consecutive RRMM patients treated with KRd between December 2015 and August 2018, in 9 Hematology Departments of Rete Ematologica Pugliese (REP). The overall response rate (ORR) was 79%, with 37% complete response (CR). Treatment with KRd led to an improvement in response regardless of age, refractory disease, and number and type of previous therapies. After a median follow-up of 18 months, median PFS was 24 months and 2y-PFS was 54%. PFS was longer in patients achieving a very good partial response (VGPR) with median PFS of 32.4 months. The relapses after prior autologous transplant (ASCT) positively impact median PFS. Several baseline disease characteristics, such as III ISS scoring or elevated LDH, and prior exposure to lenalidomide were found to negatively impact PFS. Primary refractory or relapsed myeloma patients have been treated with KRd as bridge to ASCT with a great benefit. Thirty-four (83%) reached at least a partial response after KRd and 21 (61%) performed ASCT. In transplanted patients, median PFS was not reached and 2y-PFS was 100%. The treatment discontinuation rate due to adverse events (AEs) was 18%, most commonly for lenalidomide (11%). Overall, in 10% of patients, a KRd dose reduction was necessary at least once (2.5% for carfilzomib and 8% for lenalidomide). The most frequent AE was neutropenia (44%) and anemia (41%). Infections occurred in 14% of patients. Cardiovascular events occurred in 11% of patients. Elderly patients have tolerated therapy very well, without additional side effects compared to younger patients, except for cardiac impairment. Our analysis confirmed that KRd is effective in RRMM patients. It is well tolerated and applicable to the majority of patients outside clinical trials. A longer PFS was shown in patients achieving VGPR, in those lenalidomide naïve and in patients relapsing after previous ASCT. Previous ASCT should not hamper the option for KRd therapy. Accordingly, KRd should be used as bridge regimen to ASCT with remarkable improvement in response and PFS rates. Further clinical studies are needed.
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- 2021
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19. First-line therapy with either bortezomib-melphalan-prednisone or lenalidomide-dexamethasone followed by lenalidomide for transplant-ineligible multiple myeloma patients: a pooled analysis of two randomized trials.
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Larocca A, Mina R, Offidani M, Liberati AM, Ledda A, Patriarca F, Evangelista A, Spada S, Benevolo G, Oddolo D, Innao V, Cangiolosi C, Bernardini A, Musto P, Amico V, Fraticelli V, Paris L, Giuliani N, Falcone AP, Zambello R, De Paoli L, Romano A, Palumbo A, Montefusco V, Hájek R, Boccadoro M, and Bringhen S
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Humans, Treatment Outcome, Bortezomib therapeutic use, Dexamethasone therapeutic use, Lenalidomide therapeutic use, Melphalan therapeutic use, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Prednisone therapeutic use
- Abstract
Bortezomib-melphalan-prednisone (VMP) and continuous lenalidomide-dexamethasone (Rd) represent the standard treatment of transplant-ineligible patients with newly diagnosed multiple myeloma (MM). To date, no randomized trial has compared VMP to Rd, and there is no evidence of the optimal treatment for newly diagnosed MM, particularly in patients with high-risk cytogenetics [del(17p), t(4;14) or t(14;16)]. We pooled together data from patients with newly diagnosed MM treated with VMP or Rd induction followed by lenalidomide maintenance 10 mg (Rd-R) enrolled in the GIMEMA-MM-03-05 and EMN01 trials, to evaluate the efficacy of these treatments in different subgroups of patients, focusing on those with standard- and high-risk cytogenetics. Overall, 474 patients were analyzed (VMP: 257 patients; Rd-R: 217 patients). No differences in progression-free survival (hazard ratio=0.96) and overall survival (hazard ratio=1.08) were observed between standard-risk patients treated with VMP or Rd-R, whereas among the high-risk patients, the probabilities of progression (hazard ratio=0.54) and death (hazard ratio=0.73) were lower in the patients treated with VMP than in those treated with Rd-R. In particular, standard-risk patients >75 years benefited less from VMP than from Rd-R (hazard ratio for progression-free survival=0.96; hazard ratio for overall survival=1.81). In this non-randomized analysis, VMP and Rd-R were equally effective in younger (≤75 years), standard-risk patients, while older ones (>75 years) benefited more from Rd-R. In high-risk patients, VMP improved progression-free survival and overall survival irrespective of age. The source trials are registered at ClinicalTrials.gov (NCT01063179 and NCT01093196)., (Copyright© 2020 Ferrata Storti Foundation.)
- Published
- 2020
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20. Real world Italian experience of pomalidomide plus low-dose dexamethasone in the relapsed and refractory myeloma setting: extended follow-up of a retrospective multicenter study by the 'Rete Ematologica Pugliese E Basilicata'.
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Mele G, Pastore D, Di Renzo N, Fragasso A, Guarini A, Mazza P, Musto P, Pavone V, Tarantini G, Curci P, Falcone AP, Mele A, Miccolis MR, Palazzo G, Palumbo G, Quinto AM, Reddiconto G, Rizzi R, Cascavilla N, Specchia G, and Capalbo SF
- Subjects
- Adult, Aged, Aged, 80 and over, Dexamethasone administration & dosage, Female, Follow-Up Studies, Humans, Italy, Male, Middle Aged, Multiple Myeloma pathology, Neoplasm Recurrence, Local pathology, Prognosis, Retrospective Studies, Survival Rate, Thalidomide administration & dosage, Thalidomide analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Drug Resistance, Neoplasm drug effects, Multiple Myeloma drug therapy, Neoplasm Recurrence, Local drug therapy, Salvage Therapy
- Published
- 2019
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21. Minimal residual disease and log-reduction of plasma cells are associated with superior response after double autologous stem cell transplant in younger patients with multiple myeloma.
- Author
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Rossi G, Falcone AP, Minervini MM, De Cillis GP, De Waure C, Sisti LG, Giambra V, Valente D, Chiello V, Scalzulli PR, Carella AM, and Cascavilla N
- Subjects
- Aged, Female, Humans, Lymphocyte Count, Male, Middle Aged, Multiple Myeloma mortality, Multiple Myeloma pathology, Neoplasm, Residual, Plasma Cells immunology, Prognosis, Progression-Free Survival, Recurrence, Transplantation, Autologous, Flow Cytometry methods, Hematopoietic Stem Cell Transplantation methods, Multiple Myeloma diagnosis, Multiple Myeloma therapy, Plasma Cells pathology
- Abstract
Background: Optimization of chemotherapy regimens in the treatment of multiple myeloma (MM) has led to increase the frequency of cases with complete response (CR). Nonetheless, many MM patients still experience relapse, suggesting that CR represents a suboptimal response criteria, and that new therapeutic strategies are needed after single transplant. However, the role of double autologous stem cell transplant (ASCT) as new adjunctive strategy remains to be elucidated. Indeed, we investigated the role of minimal residual disease (MRD) and log-reduction of plasma cells (PCs) as predictors of outcome and in quantifying the degree of tumor reduction after any ASCT., Methods: MRD and log-reduction were assessed by a six-color flow cytometry (FC) at different time-points: post induction, post first-, and post-second ASCT., Results: A significant difference was evidenced among the three time points for both log-reduction (P < 0.001) and MRD (P = 0.005). MRD levels after double ASCT were lower than MRD levels achieved after single ASCT (P = 0.005) and after induction (P < 0.001). Frequency of MRD positive patients after double ASCT was significantly lower rather than after the first ASCT (P = 0.008) and after induction (P = 0.004). Interestingly, a significant reduction of PFS was observed in patients with an unfavorable-risk cytogenetic (P < 0.001) and patients with MRD over 0.01% (P = 0.001) as well as log-reduction lower than 2.57 (P = 0.018) after double ASCT., Conclusions: Our results show that a better clearance of myeloma cells is observed after the double ASCT, and a longer PFS is associated with a lower MRD. © 2018 International Clinical Cytometry Society., (© 2018 International Clinical Cytometry Society.)
- Published
- 2019
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22. Prognostic or predictive value of circulating cytokines and angiogenic factors for initial treatment of multiple myeloma in the GIMEMA MM0305 randomized controlled trial.
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Saltarella I, Morabito F, Giuliani N, Terragna C, Omedè P, Palumbo A, Bringhen S, De Paoli L, Martino E, Larocca A, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Dammacco F, Boccadoro M, Vacca A, and Ria R
- Subjects
- Aged, Aged, 80 and over, Biomarkers, Tumor blood, Bone Marrow, Female, Follow-Up Studies, Humans, Logistic Models, Male, Middle Aged, Prognosis, Progression-Free Survival, ROC Curve, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Becaplermin blood, Fibroblast Growth Factor 2 blood, Hepatocyte Growth Factor blood, Multiple Myeloma blood, Multiple Myeloma drug therapy, Vascular Endothelial Growth Factor A blood
- Abstract
Background: Several new drugs are approved for treatment of patients with multiple myeloma (MM), but no validated biomarkers are available for the prediction of a clinical outcome. We aimed to establish whether pretreatment blood and bone marrow plasma concentrations of major cytokines and angiogenic factors (CAFs) of patients from a phase 3 trial of a MM treatment could have a prognostic and predictive value in terms of response to therapy and progression-free and overall survival and whether these patients could be stratified for their prognosis., Methods: Blood and bone marrow plasma levels of Ang-2, FGF-2, HGF, VEGF, PDGF-β, IL-8, TNF-α, TIMP-1, and TIMP-2 were determined at diagnosis in MM patients enrolled in the GIMEMA MM0305 randomized controlled trial by an enzyme-linked immunosorbent assay (ELISA). These levels were correlated both reciprocally and with the type of therapy and patients' characteristics and with a group of non-MM patients as controls., Results: No significant differences were detected between the blood and bone marrow plasma levels of angiogenic cytokines. A cutoff for each CAF was established. The therapeutic response of patients with blood plasma levels of CAFs lower than the cutoff was better than the response of those with higher levels in terms of percentage of responding patients and quality of response., Conclusion: FGF-2, HGF, VEGF, and PDGF-β plasma levels at diagnosis have predictive significance for response to treatment. The stratification of patients based on the levels of CAFs at diagnosis and their variations after therapy is useful to characterize different risk groups concerning outcome and response to therapy., Trial Registration: Clinical trial information can be found at the following link: NCT01063179.
- Published
- 2019
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23. Treatment Intensification With Autologous Stem Cell Transplantation and Lenalidomide Maintenance Improves Survival Outcomes of Patients With Newly Diagnosed Multiple Myeloma in Complete Response.
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Mina R, Petrucci MT, Corradini P, Spada S, Patriarca F, Cerrato C, De Paoli L, Pescosta N, Ria R, Malfitano A, Musto P, Baldini L, Guglielmelli T, Gamberi B, Mannina D, Benevolo G, Zambello R, Falcone AP, Palumbo A, Nagler A, Calafiore V, Hájek R, Spencer A, Boccadoro M, and Bringhen S
- Subjects
- Antineoplastic Agents, Alkylating adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Chemotherapy, Adjuvant, Clinical Trials, Phase III as Topic, Consolidation Chemotherapy, Female, Humans, Lenalidomide adverse effects, Maintenance Chemotherapy, Male, Middle Aged, Multicenter Studies as Topic, Multiple Myeloma diagnosis, Multiple Myeloma mortality, Neoplasm, Residual, Progression-Free Survival, Randomized Controlled Trials as Topic, Risk Factors, Time Factors, Transplantation, Autologous, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Lenalidomide administration & dosage, Multiple Myeloma therapy, Stem Cell Transplantation adverse effects, Stem Cell Transplantation mortality
- Abstract
Background: High-dose therapy with autologous stem cell transplantation (HDT-ASCT) and maintenance treatment with novel agents are the best options for patients with newly diagnosed multiple myeloma, increasing the rate of complete response (CR) and prolonging progression-free survival (PFS) and overall survival (OS). Indeed, the achievement of a CR is a predictor of long-term survival among transplant-eligible patients. However, it is unclear whether patients reaching a CR after induction treatment could receive less intense consolidation or avoid maintenance therapy., Patients and Methods: We analyzed CR patients treated in 2 phase III trials, GIMEMA-RV-MM-PI-209 and RV-MM-EMN-441, to compare HDT-ASCT with an R-Alk (lenalidomide, alkylator) regimen as consolidation, and lenalidomide (R) maintenance with no maintenance. The primary endpoints were PFS, second PFS (PFS2), and OS from consolidation and maintenance (_m)., Results: Overall, the data from 166 patients in CR were analyzed, 95 in the HDT-ASCT group and 71 in the R-Alk group. The CR patients who received HDT-ASCT had a better PFS (hazard ratio [HR], 0.55; P = .01), PFS2 (HR, 0.46; P = .02), and OS (HR, 0.42; P = .03) compared with patients randomized to R-Alk. The survival benefit with HDT-ASCT was confirmed among all the subgroups, according to age, International Staging System (ISS stage, cytogenetic profile, and receipt of maintenance therapy. CR patients who received lenalidomide maintenance had a better PFS_m (4 years: 54% vs. 19%; HR, 0.43; P = .02) compared with those who received no maintenance. However, no difference was observed in terms of PFS2_m (4 years: 72% vs. 58%; HR, 0.83; P = .67) and OS_m (4 years: 79% vs. 72%; HR, 0.82; P = .73) with maintenance therapy., Conclusion: Even in CR patients, outcomes were improved by an intensified approach with HDT-ASCT consolidation and lenalidomide-based maintenance therapy., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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24. Autologous transplant vs oral chemotherapy and lenalidomide in newly diagnosed young myeloma patients: a pooled analysis.
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Gay F, Oliva S, Petrucci MT, Montefusco V, Conticello C, Musto P, Catalano L, Evangelista A, Spada S, Campbell P, Ria R, Salvini M, Offidani M, Carella AM, Omedé P, Liberati AM, Troia R, Cafro AM, Malfitano A, Falcone AP, Caravita T, Patriarca F, Nagler A, Spencer A, Hajek R, Palumbo A, and Boccadoro M
- Subjects
- Administration, Oral, Adult, Aged, Clinical Trials, Phase III as Topic, Humans, Lenalidomide, Middle Aged, Multiple Myeloma mortality, Salvage Therapy, Thalidomide therapeutic use, Transplantation, Autologous, Multiple Myeloma therapy, Stem Cell Transplantation, Thalidomide analogs & derivatives
- Abstract
In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival 1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival 2 (PFS2), overall survival (OS). A total of 268 patients were randomized to 2 courses of melphalan 200 mg/m
2 and ASCT (MEL200-ASCT) and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 (median: 42 vs 24 months, HR 0.53; P<0.001), PFS2 (4 years: 71 vs 54%, HR 0.53, P<0.001) and OS (4 years: 84 vs 70%, HR 0.51, P<0.001) compared with CC+R. The advantage was noticed in good and bad prognosis patients. Only 53% of patients relapsing from CC+R received ASCT at first relapse. Upfront ASCT significantly reduced the risk of death (HR 0.51; P=0.007) in comparison with salvage ASCT. In conclusion, these data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.- Published
- 2017
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25. Ruxolitinib - better prognostic impact in low-intermediate 1 risk score: evaluation of the 'rete ematologica pugliese' (REP) in primary and secondary myelofibrosis.
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Mazza P, Specchia G, Di Renzo N, Cascavilla N, Tarantini G, Capalbo SF, Urbano T, Albano F, Giovannni R, Falcone AP, Santeramo MT, Spinosa G, and Pisconti S
- Subjects
- Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Myeloproliferative Disorders diagnosis, Myeloproliferative Disorders etiology, Nitriles, Primary Myelofibrosis diagnosis, Prognosis, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Pyrazoles administration & dosage, Pyrazoles adverse effects, Pyrimidines, Survival Analysis, Time Factors, Treatment Outcome, Myeloproliferative Disorders drug therapy, Myeloproliferative Disorders mortality, Primary Myelofibrosis drug therapy, Primary Myelofibrosis mortality, Protein Kinase Inhibitors therapeutic use, Pyrazoles therapeutic use
- Abstract
We evaluated ruxolitinib in 65 patients with myelofibrosis according to age, sex, time of diagnosis, grade of fibrosis, prognostic score risk, Janus kinase (JAK) status, primary or secondary myelofibrosis, previous treatment, and dosage. Outcome measures were response rate, time to response, duration of response, and event-free survival and survival. Kaplan and Meier curves show a significant difference in event-free survival according to the prognostic score, in favor of patients with low int1 (p = 0.0009). The Cox stepwise model confirmed the result, the int2 high-risk score being the most powerful negative independent parameter (0.001), followed by JAK (0.008); other parameters, such as diagnosis more than 5 years earlier, grade III-IV fibrosis, and ruxolitinib dose have a negligible impact. Time to response was shorter (p = 0.001) in primary myelofibrosis. In conclusion, ruxolitinib is effective, with a better outcome in patients with a low-int1 risk score. This may suggest considering an earlier administration in the disease course.
- Published
- 2017
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26. A phase 2 study of three low-dose intensity subcutaneous bortezomib regimens in elderly frail patients with untreated multiple myeloma.
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Larocca A, Bringhen S, Petrucci MT, Oliva S, Falcone AP, Caravita T, Villani O, Benevolo G, Liberati AM, Morabito F, Montefusco V, Passera R, De Rosa L, Omedé P, Vincelli ID, Spada S, Carella AM, Ponticelli E, Derudas D, Genuardi M, Guglielmelli T, Nozzoli C, Aghemo E, De Paoli L, Conticello C, Musolino C, Offidani M, Boccadoro M, Sonneveld P, and Palumbo A
- Subjects
- Aged, Aged, 80 and over, Cyclophosphamide, Disease-Free Survival, Female, Humans, Male, Melphalan administration & dosage, Multiple Myeloma mortality, Prednisone administration & dosage, Survival Rate, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bortezomib administration & dosage, Multiple Myeloma drug therapy
- Abstract
This phase 2 trial evaluated three low-dose intensity subcutaneous bortezomib-based treatments in patients ⩾75 years with newly diagnosed multiple myeloma (MM). Patients received subcutaneous bortezomib plus oral prednisone (VP, N=51) or VP plus cyclophosphamide (VCP, N=51) or VP plus melphalan (VMP, N=50), followed by bortezomib maintenance, and half of the patients were frail. Response rate was 64% with VP, 67% with VCP and 86% with VMP, and very good partial response rate or better was 26%, 28.5% and 49%, respectively. Median progression-free survival was 14.0, 15.2 and 17.1 months, and 2-year OS was 60%, 70% and 76% in VP, VCP, VMP, respectively. At least one drug-related grade ⩾3 non-hematologic adverse event (AE) occurred in 22% of VP, 37% of VCP and 33% of VMP patients; the discontinuation rate for AEs was 12%, 14% and 20%, and the 6-month rate of toxicity-related deaths was 4%, 4% and 8%, respectively. The most common grade ⩾3 AEs included infections (8-20%), and constitutional (10-14%) and cardiovascular events (4-12%); peripheral neuropathy was limited (4-6%). Bortezomib maintenance was effective and feasible. VP, VCP and VMP regimens demonstrated no substantial difference. Yet, toxicity was higher with VMP, suggesting that a two-drug combination followed by maintenance should be preferred in frail patients.
- Published
- 2016
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27. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma.
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Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, Falcone AP, De Paoli L, Pietrantuono G, Gentili S, Musolino C, Giuliani N, Bernardini A, Conticello C, Pulini S, Ciccone G, Maisnar V, Ruggeri M, Zambello R, Guglielmelli T, Ledda A, Liberati AM, Montefusco V, Hajek R, Boccadoro M, and Palumbo A
- Subjects
- Aged, Aged, 80 and over, Demography, Disease-Free Survival, Drug Therapy, Combination, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Lenalidomide, Male, Middle Aged, Thalidomide adverse effects, Thalidomide therapeutic use, Treatment Outcome, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Thalidomide analogs & derivatives
- Abstract
Lenalidomide-dexamethasone improved outcome in newly diagnosed elderly multiple myeloma patients. We randomly assigned 662 patients who were age ≥65 years or transplantation-ineligible to receive induction with melphalan-prednisone-lenalidomide (MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) or lenalidomide plus low-dose dexamethasone (Rd). The primary end point was progression-free survival (PFS) in triplet (MPR and CPR) vs doublet (Rd) lenalidomide-containing regimens. After a median follow-up of 39 months, the median PFS was 22 months for the triplet combinations and 21 months for the doublet (P = .284). The median overall survival (OS) was not reached in either arms, and the 4-year OS was 67% for the triplet and 58% for the doublet arms (P = .709). By considering the 3 treatment arms separately, no difference in outcome was detected among MPR, CPR, and Rd. The most common grade ≥3 toxicity was neutropenia: 64% in MPR, 29% in CPR, and 25% in Rd patients (P < .0001). Grade ≥3 nonhematologic toxicities were similar among arms and were mainly infections (6.5% to 11%), constitutional (3.5% to 9.5%), and cardiac (4.5% to 6%), with no difference among the arms. In conclusion, in the overall population, the alkylator-containing triplets MPR and CPR were not superior to the alkylator-free doublet Rd, which was associated with lower toxicity. This study was registered at www.clinicaltrials.gov as #NCT01093196., (© 2016 by The American Society of Hematology.)
- Published
- 2016
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28. Long-term results of the GIMEMA VEL-03-096 trial in MM patients receiving VTD consolidation after ASCT: MRD kinetics' impact on survival.
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Ferrero S, Ladetto M, Drandi D, Cavallo F, Genuardi E, Urbano M, Caltagirone S, Grasso M, Rossini F, Guglielmelli T, Cangialosi C, Liberati AM, Callea V, Carovita T, Crippa C, De Rosa L, Pisani F, Falcone AP, Pregno P, Oliva S, Terragna C, Musto P, Passera R, Boccadoro M, and Palumbo A
- Subjects
- Adult, Aged, Boronic Acids administration & dosage, Bortezomib, Dexamethasone administration & dosage, Female, Follow-Up Studies, Gene Expression, Humans, Male, Middle Aged, Multiple Myeloma genetics, Multiple Myeloma mortality, Multiple Myeloma pathology, Neoplasm, Residual, Polymerase Chain Reaction, Pyrazines administration & dosage, Recurrence, Survival Analysis, Thalidomide administration & dosage, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols, Hematopoietic Stem Cell Transplantation, Immunoglobulin Heavy Chains genetics, Multiple Myeloma therapy
- Abstract
Polymerase chain reaction (PCR)-based minimal residual disease (MRD) analysis is a useful prognostic tool in multiple myeloma (MM), although its long-term impact still needs to be addressed. This report presents the updated results of the GIMEMA-VEL-03-096 trial. Thirty-nine MM patients receiving bortezomib-thalidomide-dexamethasone after autologous transplantation were monitored for MRD by both nested and real-time quantitative-PCR until relapse. Our data confirm the strong impact of MRD on survival: overall survival was 72% at 8 years median follow-up for patients in major MRD response versus 48% for those experiencing MRD persistence (P=0.041). In addition, MRD kinetics resulted predictive for relapse: indeed median remission duration was not reached for patients in major MRD response, 38 months for those experiencing MRD reappearance and 9 months for patients with MRD persistence (P<0.001). Moreover: (1) 26 patients achieving major MRD response (67%) benefit of excellent disease control (median TNT: 42 months); (2) MRD reappearance heralds relapse, with a TNT comparable to that of MRD persistence (9 versus 10 months, P=0.706); (3) the median lag between MRD reappearance and need for salvage treatment is 9 months. These results suggest the usefulness of a long-term MRD monitoring in MM patients and the need for maintenance or pre-emptive treatments ensuring durable responses.
- Published
- 2015
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29. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival.
- Author
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Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, Patriarca F, Levi A, Benevolo G, Vincelli ID, Grasso M, Franceschini L, Gottardi D, Zambello R, Montefusco V, Falcone AP, Omedé P, Marasca R, Morabito F, Mina R, Guglielmelli T, Nozzoli C, Passera R, Gaidano G, Offidani M, Ria R, Petrucci MT, Musto P, Boccadoro M, and Cavo M
- Subjects
- Adult, Aged, Antineoplastic Combined Chemotherapy Protocols adverse effects, Boronic Acids administration & dosage, Boronic Acids adverse effects, Bortezomib, Disease-Free Survival, Female, Follow-Up Studies, Humans, Induction Chemotherapy, Kaplan-Meier Estimate, Maintenance Chemotherapy, Male, Melphalan administration & dosage, Melphalan adverse effects, Middle Aged, Neutropenia chemically induced, Peripheral Nervous System Diseases chemically induced, Prednisone administration & dosage, Prednisone adverse effects, Pyrazines administration & dosage, Pyrazines adverse effects, Thalidomide administration & dosage, Thalidomide adverse effects, Thrombocytopenia chemically induced, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy, Multiple Myeloma mortality
- Abstract
Purpose: Bortezomib-melphalan-prednisone (VMP) has improved overall survival in multiple myeloma. This randomized trial compared VMP plus thalidomide (VMPT) induction followed by bortezomib-thalidomide maintenance (VMPT-VT) with VMP in patients with newly diagnosed multiple myeloma., Patients and Methods: We randomly assigned 511 patients who were not eligible for transplantation to receive VMPT-VT (nine 5-week cycles of VMPT followed by 2 years of VT maintenance) or VMP (nine 5-week cycles without maintenance)., Results: In the initial analysis with a median follow-up of 23 months, VMPT-VT improved complete response rate from 24% to 38% and 3-year progression-free-survival (PFS) from 41% to 56% compared with VMP. In this analysis, median follow-up was 54 months. The median PFS was significantly longer with VMPT-VT (35.3 months) than with VMP (24.8 months; hazard ratio [HR], 0.58; P < .001). The time to next therapy was 46.6 months in the VMPT-VT group and 27.8 months in the VMP group (HR, 0.52; P < .001). The 5-year overall survival (OS) was greater with VMPT-VT (61%) than with VMP (51%; HR, 0.70; P = .01). Survival from relapse was identical in both groups (HR, 0.92; P = .63). In the VMPT-VT group, the most frequent grade 3 to 4 adverse events included neutropenia (38%), thrombocytopenia (22%), peripheral neuropathy (11%), and cardiologic events (11%). All of these, except for thrombocytopenia, were significantly more frequent in the VMPT-VT patients., Conclusion: Bortezomib and thalidomide significantly improved OS in multiple myeloma patients not eligible for transplantation.
- Published
- 2014
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30. Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials.
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Bringhen S, Mateos MV, Zweegman S, Larocca A, Falcone AP, Oriol A, Rossi D, Cavalli M, Wijermans P, Ria R, Offidani M, Lahuerta JJ, Liberati AM, Mina R, Callea V, Schaafsma M, Cerrato C, Marasca R, Franceschini L, Evangelista A, Teruel AI, van der Holt B, Montefusco V, Ciccone G, Boccadoro M, San Miguel J, Sonneveld P, and Palumbo A
- Subjects
- Age Factors, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Cause of Death, Female, Humans, Male, Multiple Myeloma drug therapy, Multiple Myeloma pathology, Neoplasm Staging, Prognosis, Proportional Hazards Models, Randomized Controlled Trials as Topic, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols adverse effects, Multiple Myeloma mortality
- Abstract
Thalidomide and bortezomib are extensively used to treat elderly myeloma patients. In these patients, treatment-related side effects are frequent and full drug doses difficult to tolerate. We retrospectively analyzed data from 1435 elderly patients enrolled in 4 European phase III trials including thalidomide and/or bortezomib. After a median follow up of 33 months (95%CI: 10-56 months), 513 of 1435 patients (36%) died; median overall survival was 50 months (95%CI: 46-60 months). The risk of death was increased in patients aged 75 years or over (HR 1.44, 95%CI: 1.20-1.72; P<0.001), in patients with renal failure (HR 2.02, 95%CI: 1.51-2.70; P<0.001), in those who experienced grade 3-4 infections, cardiac or gastrointestinal adverse events during treatment (HR 2.53, 95%CI: 1.75-3.64; P<0.001) and in those who required drug discontinuation due to adverse events (HR 1.67, 95%CI; 1.12-2.51; P=0.01). This increased risk was restricted to the first six months after occurrence of adverse events or drug discontinuation and declined over time. More intensive approaches, such as the combination of bortezomib-thalidomide, negatively affected outcome. Bortezomib-based combinations may overcome the negative impact of renal failure. Age 75 years or over or renal failure at presentation, occurrence of infections, cardiac or gastrointestinal adverse events negatively affected survival. A detailed geriatric assessment, organ evaluation and less intense individualized approaches are suggested in elderly unfit subjects.
- Published
- 2013
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31. Lenalidomide can induce long-term responses in patients with multiple myeloma relapsing after multiple chemotherapy lines, in particular after allogeneic transplant.
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Spina F, Montefusco V, Crippa C, Citro A, Sammassimo S, Olivero B, Gentili S, Galli M, Guglielmelli T, Rossi D, Falcone AP, Grasso M, Patriarca F, De Muro M, and Corradini P
- Subjects
- Adult, Aged, Aged, 80 and over, Cytogenetics, Dexamethasone administration & dosage, Dexamethasone therapeutic use, Humans, Immunoglobulin Isotypes immunology, Lenalidomide, Middle Aged, Multiple Myeloma drug therapy, Multiple Myeloma immunology, Multiple Myeloma mortality, Recurrence, Survival Analysis, Thalidomide therapeutic use, Time Factors, Transplantation, Homologous, Treatment Outcome, Antineoplastic Agents therapeutic use, Multiple Myeloma therapy, Stem Cell Transplantation, Thalidomide analogs & derivatives
- Abstract
Evidence of long-term response to lenalidomide in heavily pretreated patients with multiple myeloma is lacking. This study sought to assess whether long-term responders exist, long-term responders' characteristics, and predictive factors of a long-term response. One hundred and four patients with multiple myeloma treated with lenalidomide and dexamethasone after ≥2 therapy lines (median, 3) were analyzed. Long-term response was defined as at least a partial response (≥PR) lasting ≥12 months. The overall response rate was 73%, and 80.3% of the responses were achieved within 5 months. The median response was 14.3 months. Patients evaluable for long-term response numbered 87, and a total of 47% were long-term responders. Compared to non-long-term responders, long-term responders had better overall survival, less light-chain multiple myeloma, and higher incidence of t(11;14). Previous allogeneic transplant (alloSCT) and the response quality predicted a long-term response. In conclusion, patients treated with lenalidomide can become long-term responders; alloSCT and response quality predict long-term response.
- Published
- 2011
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32. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients.
- Author
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Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, Gentili S, Patriarca F, Nozzoli C, Levi A, Guglielmelli T, Benevolo G, Callea V, Rizzo V, Cangialosi C, Musto P, De Rosa L, Liberati AM, Grasso M, Falcone AP, Evangelista A, Cavo M, Gaidano G, Boccadoro M, and Palumbo A
- Subjects
- Aged, Boronic Acids adverse effects, Bortezomib, Disease-Free Survival, Drug Administration Schedule, Female, Humans, Incidence, Kaplan-Meier Estimate, Male, Melphalan administration & dosage, Melphalan adverse effects, Middle Aged, Multiple Myeloma mortality, Multiple Myeloma pathology, Neoplasm Staging, Peripheral Nervous System Diseases chemically induced, Peripheral Nervous System Diseases epidemiology, Prednisone administration & dosage, Prednisone adverse effects, Pyrazines adverse effects, Thalidomide administration & dosage, Thalidomide adverse effects, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Boronic Acids administration & dosage, Multiple Myeloma drug therapy, Pyrazines administration & dosage
- Abstract
In a recent phase 3 trial, bortezomib-melphalan-prednisone-thalidomide followed by maintenance treatment with bortezomib-thalidomide demonstrated superior efficacy compared with bortezomib-melphalan-prednisone. To decrease neurologic toxicities, the protocol was amended and patients in both arms received once-weekly instead of the initial twice-weekly bortezomib infusions: 372 patients received once-weekly and 139 twice-weekly bortezomib. In this post-hoc analysis we assessed the impact of the schedule change on clinical outcomes and safety. Long-term outcomes appeared similar: 3-year progression-free survival rate was 50% in the once-weekly and 47% in the twice-weekly group (P > .999), and 3-year overall survival rate was 88% and 89%, respectively (P = .54). The complete response rate was 30% in the once-weekly and 35% in the twice-weekly group (P = .27). Nonhematologic grade 3/4 adverse events were reported in 35% of once-weekly patients and 51% of twice-weekly patients (P = .003). The incidence of grade 3/4 peripheral neuropathy was 8% in the once-weekly and 28% in the twice-weekly group (P < .001); 5% of patients in the once-weekly and 15% in the twice-weekly group discontinued therapy because of peripheral neuropathy (P < .001). This improvement in safety did not appear to affect efficacy. This study is registered at http://www.clinicaltrials.gov as NCT01063179.
- Published
- 2010
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33. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial.
- Author
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Palumbo A, Bringhen S, Rossi D, Cavalli M, Larocca A, Ria R, Offidani M, Patriarca F, Nozzoli C, Guglielmelli T, Benevolo G, Callea V, Baldini L, Morabito F, Grasso M, Leonardi G, Rizzo M, Falcone AP, Gottardi D, Montefusco V, Musto P, Petrucci MT, Ciccone G, and Boccadoro M
- Subjects
- Boronic Acids administration & dosage, Boronic Acids adverse effects, Bortezomib, Disease-Free Survival, Humans, Kaplan-Meier Estimate, Melphalan administration & dosage, Melphalan adverse effects, Multiple Myeloma mortality, Prednisone administration & dosage, Prednisone adverse effects, Proportional Hazards Models, Pyrazines administration & dosage, Pyrazines adverse effects, Thalidomide administration & dosage, Thalidomide adverse effects, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
Purpose: The combination of bortezomib-melphalan-prednisone (VMP) is a new standard of care for newly diagnosed multiple myeloma. This phase III study examined the efficacy of the four-drug combination of bortezomib-melphalan-prednisone-thalidomide (VMPT) followed by maintenance with bortezomib-thalidomide (VMPT-VT) compared with VMP treatment alone in untreated multiple myeloma patients who are ineligible for autologous stem-cell transplantation., Patients and Methods: A total of 511 patients were randomly assigned to receive nine cycles of VMPT followed by continuous VT as maintenance, or nine cycles of VMP at the same doses with no additional therapy. The primary end point was progression-free survival., Results: The 3-year estimates of progression-free survival were 56% in patients receiving VMPT-VT and 41% in those receiving VMP (hazard ratio [HR], 0.67; 95% CI, 0.50 to 0.90; P = .008). At 3 years, the cumulative proportions of patients who did not go on to the next therapy were 72% with VMPT-VT and 60% with VMP (HR, 0.58; 95% CI, 0.50 to 0.90; P = .007). Complete response rates were 38% in the VMPT-VT group and 24% in the VMP group (P < .001). The 3-year overall survival was 89% with VMPT-VT and 87% with VMP (HR, 0.92; 95% CI, 0.53 to 1.60; P = .77). Grade 3 to 4 neutropenia (38% v 28%; P = .02), cardiologic events (10% v 5%; P = .04), and thromboembolic events (5% v 2%; P = .08) were more frequent among patients assigned to the VMPT-VT group than among those assigned to the VMP group; treatment-related deaths were 4% with VMPT-VT and 3% with VMP., Conclusion: VMPT followed by VT as maintenance was superior to VMP alone in patients with multiple myeloma who are ineligible for autologous stem-cell transplantation.
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- 2010
- Full Text
- View/download PDF
34. Lenalidomide, melphalan, prednisone and thalidomide (RMPT) for relapsed/refractory multiple myeloma.
- Author
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Palumbo A, Larocca A, Falco P, Sanpaolo G, Falcone AP, Federico V, Canepa L, Crugnola M, Genuardi M, Magarotto V, Petrucci MT, and Boccadoro M
- Subjects
- Aged, Aged, 80 and over, Disease Progression, Female, Humans, Lenalidomide, Male, Melphalan administration & dosage, Middle Aged, Multiple Myeloma pathology, Neoplasm Recurrence, Local pathology, Prednisone administration & dosage, Remission Induction, Survival Rate, Thalidomide administration & dosage, Thalidomide analogs & derivatives, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Drug Resistance, Neoplasm, Multiple Myeloma drug therapy, Neoplasm Recurrence, Local drug therapy, Salvage Therapy
- Abstract
This multicenter, open-label, non-comparative phase II trial evaluated the safety and efficacy of salvage therapy with lenalidomide, melphalan, prednisone and thalidomide (RMPT) in patients with relapsed/refractory multiple myeloma (MM). Oral lenalidomide (10 mg/day) was administered on days 1-21, and oral melphalan (0.18 mg/kg) and oral prednisone (2 mg/kg) on days 1-4 of each 28-day cycle. Thalidomide was administered at 50 mg/day or 100 mg/day on days 1-28; six cycles were administered in total. Maintenance included lenalidomide 10 mg/day on days 1-21, until unacceptable adverse events or disease progression. Aspirin (100 mg/day) was given as thromboprophylaxis. A total of 44 patients with relapsed/refractory MM were enrolled and 75% achieved at least a partial response (PR), including 32% very good PR (VGPR) and 2% complete response (CR). The 1-year progression-free survival (PFS) was 51% and the 1-year overall survival (OS) from study entry was 72%. Grade 4 hematologic adverse events included neutropenia (18%), thrombocytopenia (7%) and anemia (2%). Grade 3 non-hematologic adverse events were infections (14%), neurological toxicity (4.5%) and fatigue (7%). No grade 3/4 thromboembolic events or peripheral neuropathy were reported. In conclusion, RMPT is an active salvage therapy with good efficacy and manageable side effects. This study represents the basis for larger phase III randomized trials.
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- 2010
- Full Text
- View/download PDF
35. Melphalan 200 mg/m(2) versus melphalan 100 mg/m(2) in newly diagnosed myeloma patients: a prospective, multicenter phase 3 study.
- Author
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Palumbo A, Bringhen S, Bruno B, Falcone AP, Liberati AM, Grasso M, Ria R, Pisani F, Cangialosi C, Caravita T, Levi A, Meloni G, Nozza A, Pregno P, Gabbas A, Callea V, Rizzo M, Annino L, De Stefano V, Musto P, Baldi I, Cavallo F, Petrucci MT, Massaia M, and Boccadoro M
- Subjects
- Adult, Aged, Algorithms, Antigens, CD34 metabolism, Antineoplastic Agents, Alkylating administration & dosage, Bone Marrow Transplantation immunology, Bone Marrow Transplantation methods, Combined Modality Therapy, Dose-Response Relationship, Drug, Female, Humans, Male, Middle Aged, Multiple Myeloma mortality, Myeloablative Agonists administration & dosage, Neoadjuvant Therapy, Transplantation Conditioning methods, Transplantation, Autologous, Melphalan administration & dosage, Multiple Myeloma therapy
- Abstract
High-dose (200 mg/m(2), MEL200) and intermediate-dose melphalan (100 mg/m(2), MEL100) showed significant activity in myeloma. In a phase 3 study, 298 patients were randomly assigned to receive 2 autologous transplantations after conditioning with MEL200 or MEL100. Ninety-six of 149 (64%) completed MEL200 and 103 of 149 (69%) MEL100. Best response to MEL200 was: complete remission 22 of 149 (15%); partial remission 95 of 149 (64%), for an overall response rate of 79%. Best response to MEL100 was: complete remission 12 of 149 (8%); partial remission 95 of 149 (64%), for an overall response rate of 72%. Overall survival did not differ (P = .13); median progression-free survival (31.4 vs 26.2 months, P = .01), median time to progression (34.4 vs 27.0 months, P = .014) were longer in the MEL200. Treatment-related mortality was 3.1% in the MEL200 and 2.9% in the MEL100 group. Severe neutropenia and infections were marginally superior, whereas severe thrombocytopenia, mucositis, gastrointestinal adverse events, and the overall occurrence of at least 1 nonhematologic grade 3 or 4 adverse event were significantly higher in the MEL200 cohort. We conclude that MEL200 leads to longer remission duration and should be considered the standard conditioning regimen for autologous transplantation. This study was registered at www.clinicaltrials.gov as #NCT00950768.
- Published
- 2010
- Full Text
- View/download PDF
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