27 results on '"San-Miguel, J."'
Search Results
2. 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
- Adult, Aged, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Dexamethasone administration & dosage, Female, Humans, Lenalidomide administration & dosage, Male, Middle Aged, Multiple Myeloma psychology, Pain Measurement, Patient Reported Outcome Measures, Progression-Free Survival, Quality of Life, Recurrence, Surveys and Questionnaires, Treatment Outcome, Multiple Myeloma drug therapy, Salvage Therapy psychology
- 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
- Full Text
- View/download PDF
3. Comparison of efficacy from two different dosing regimens of bortezomib: an exposure-response analysis.
- Author
-
Parasrampuria DA, He J, Zhang L, Muresan B, Hu P, Nemat S, Hashim M, Lam A, Appiani C, Cavo M, Dimopoulos MA, San-Miguel J, and Mateos MV
- Subjects
- Aged, Aged, 80 and over, Antibodies, Monoclonal administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bortezomib adverse effects, Clinical Trials, Phase III as Topic statistics & numerical data, Dose-Response Relationship, Drug, Drug Administration Schedule, Female, Humans, Kaplan-Meier Estimate, Logistic Models, Male, Melphalan administration & dosage, Middle Aged, Multicenter Studies as Topic statistics & numerical data, Prednisone administration & dosage, Progression-Free Survival, Proportional Hazards Models, Proteasome Inhibitors adverse effects, Proteasome Inhibitors therapeutic use, Randomized Controlled Trials as Topic statistics & numerical data, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bortezomib administration & dosage, Multiple Myeloma drug therapy, Proteasome Inhibitors administration & dosage
- Abstract
Bortezomib is a first-in-class proteasome inhibitor, approved for the treatment of multiple myeloma. The originally approved dosing schedule of bortezomib results in significant toxicities that require dose interruptions and discontinuations. Consequentially, less frequent dosing has been explored to optimise bortezomib's benefit-risk profile. Here, we performed exposure-response analysis to compare the efficacy of the original bortezomib dosing regimen with less frequent dosing of bortezomib over nine 6-week treatment cycles using data from the VISTA clinical trial and the control arm of the ALCYONE clinical trial. The relationship between cumulative bortezomib dose and clinical response was evaluated with a univariate logit model. The median cumulative bortezomib dose was higher in ALCYONE versus VISTA (42·2 vs. 38·5 mg/m
2 ) and ALCYONE patients stayed on treatment longer (mean: 7·2 vs. 5·8 cycles). For all endpoints and regimens, probability of clinical response correlated with cumulative bortezomib dose. Similar to results observed for VISTA, overall survival was longer in ALCYONE patients with ≥ 39·0 versus < 39·0 mg/m2 cumulative dose (hazard ratio, 0·119; P < 0·0001). Less frequent bortezomib dosing results in comparable efficacy, and a higher cumulative dose than the originally approved bortezomib dosing schedule, which may be in part be due to reduced toxicity and fewer dose reductions/interruptions., (© 2020 British Society for Haematology and John Wiley & Sons Ltd.)- Published
- 2020
- Full Text
- View/download PDF
4. Pembrolizumab combined with lenalidomide and low-dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE-023 study.
- Author
-
Mateos MV, Orlowski RZ, Ocio EM, Rodríguez-Otero P, Reece D, Moreau P, Munshi N, Avigan DE, Siegel DS, Ghori R, Farooqui MZH, Marinello P, and San-Miguel J
- Subjects
- Antibodies, Monoclonal, Humanized pharmacology, Dexamethasone pharmacology, Female, Humans, Lenalidomide pharmacology, Male, Middle Aged, Multiple Myeloma pathology, Antibodies, Monoclonal, Humanized therapeutic use, Dexamethasone therapeutic use, Lenalidomide therapeutic use, Multiple Myeloma drug therapy
- Published
- 2019
- Full Text
- View/download PDF
5. Elotuzumab plus lenalidomide/dexamethasone for relapsed or refractory multiple myeloma: ELOQUENT-2 follow-up and post-hoc analyses on progression-free survival and tumour growth.
- Author
-
Dimopoulos MA, Lonial S, White D, Moreau P, Palumbo A, San-Miguel J, Shpilberg O, Anderson K, Grosicki S, Spicka I, Walter-Croneck A, Magen H, Mateos MV, Belch A, Reece D, Beksac M, Bleickardt E, Poulart V, Sheng J, Sy O, Katz J, Singhal A, and Richardson P
- Subjects
- Aged, Antibodies, Monoclonal, Humanized administration & dosage, Antibodies, Monoclonal, Humanized adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Dexamethasone administration & dosage, Dexamethasone adverse effects, Female, Follow-Up Studies, Humans, Immunoglobulins blood, Kaplan-Meier Estimate, Lenalidomide, Male, Middle Aged, Multiple Myeloma pathology, Recurrence, Thalidomide administration & dosage, Thalidomide adverse effects, Thalidomide analogs & derivatives, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
The randomized phase III ELOQUENT-2 study (NCT01239797) evaluated the efficacy and safety of elotuzumab + lenalidomide/dexamethasone (ELd) versus lenalidomide/dexamethasone (Ld) in relapsed/refractory multiple myeloma. ELd reduced the risk of disease progression/death by 30% versus Ld (hazard ratio [HR] 0·70). Median time from diagnosis was 3·5 years. We present extended 3-year follow-up data. Endpoints included progression-free survival (PFS), overall response rate (ORR) and interim overall survival (OS). Exploratory post-hoc analyses included impact of time from diagnosis and prior lines of therapy on PFS, and serum M-protein dynamic modelling. ORR was 79% (ELd) and 66% (Ld) (P = 0·0002). ELd reduced the risk of disease progression/death by 27% versus Ld (HR 0·73; P = 0·0014). Interim OS demonstrated a trend in favour of ELd (P = 0·0257); 1-, 2- and 3-year rates with ELd versus Ld were: 91% versus 83%, 73% versus 69% and 60% versus 53%. In patients with ≥ median time from diagnosis and one prior therapy, ELd resulted in a 53% reduction in the risk of progression/death versus Ld (HR 0·47). Serum M-protein dynamic modelling showed slower tumour regrowth with ELd. Adverse events were comparable between arms. ELd provided a durable and clinically relevant improvement in efficacy, with minimal incremental toxicity., (© 2017 John Wiley & Sons Ltd.)
- Published
- 2017
- Full Text
- View/download PDF
6. Carfilzomib, lenalidomide, and dexamethasone in patients with relapsed multiple myeloma categorised by age: secondary analysis from the phase 3 ASPIRE study.
- Author
-
Dimopoulos MA, Stewart AK, Masszi T, Špička I, Oriol A, Hájek R, Rosiñol L, Siegel D, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak A, San-Miguel J, Ludwig H, Palumbo A, Obreja M, Aggarwal S, and Moreau P
- Subjects
- Adult, Age Factors, Aged, Aged, 80 and over, Dexamethasone administration & dosage, Female, Humans, Kaplan-Meier Estimate, Lenalidomide, Male, Middle Aged, Oligopeptides administration & dosage, Recurrence, Thalidomide administration & dosage, Thalidomide analogs & derivatives, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
A primary analysis of the ASPIRE study found that the addition of carfilzomib to lenalidomide and dexamethasone (carfilzomib group) significantly improved progression-free survival (PFS) compared with lenalidomide and dexamethasone alone (control group) in patients with relapsed multiple myeloma (RMM). This post hoc analysis examined outcomes from ASPIRE in patients categorised by age. In the carfilzomib group, 103/396 patients were ≥70 years old, and in the control group, 115/396 patients were ≥70 years old. Median PFS for patients <70 years old was 28·6 months for the carfilzomib group versus 17·6 months for the control group [hazard ratio (HR), 0·701]. Median PFS for patients ≥70 years old was 23·8 months for the carfilzomib group versus 16·0 months for the control group (HR, 0·753). For patients <70 years the overall response rate (ORR) was 86·0% (carfilzomib group) and 66·9% (control group); for patients ≥70 years old the ORR was 90·3% (carfilzomib group) and 66·1% (control group). Within the carfilzomib group, grade ≥3 cardiovascular adverse events occurred more frequently among patients ≥70 years old compared with patients <70 years old. Carfilzomib-lenalidomide-dexamethasone has a favourable benefit-risk profile for patients with RMM, including elderly patients ≥70 years old., Trial Registration: clinicaltrials.gov identifier: NCT01080391., (© 2017 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.)
- Published
- 2017
- Full Text
- View/download PDF
7. Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma.
- Author
-
Mateos MV, Granell M, Oriol A, Martinez-Lopez J, Blade J, Hernandez MT, Martín J, Gironella M, Lynch M, Bleickardt E, Paliwal P, Singhal A, and San-Miguel J
- Subjects
- Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, Dexamethasone administration & dosage, Drug Resistance, Neoplasm, Female, Humans, Male, Middle Aged, Multiple Myeloma mortality, Neoplasm Staging, Recurrence, Retreatment, Survival Analysis, Thalidomide administration & dosage, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy, Multiple Myeloma pathology
- Abstract
Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction. Twenty-six (65%) patients had ≥1 dose reduction/discontinuation due to an AE, none related to elotuzumab. Overall response rate was 38%; median progression-free survival was 3·9 months. Median overall survival was 16·3 months and the 1-year survival rate was 63%. Minimal incremental toxicity was observed with addition of elotuzumab to thalidomide/dexamethasone with or without cyclophosphamide, and efficacy data suggest clinical benefit in a highly pre-treated population. Elotuzumab combined with thalidomide may provide an additional treatment option for patients with RRMM., (© 2016 John Wiley & Sons Ltd.)
- Published
- 2016
- Full Text
- View/download PDF
8. Phase I/II study of weekly PM00104 (Zalypsis®) in patients with relapsed/refractory multiple myeloma.
- Author
-
Ocio EM, Oriol A, Bladé J, Teruel AI, Martín J, de la Rubia J, Gutiérrez NC, Rodríguez Díaz-Pavón J, Martínez González S, Coronado C, Fernández-García EM, Siguero Gómez M, Fernández-Teruel C, and San Miguel J
- Subjects
- Adult, Aged, Drug Resistance, Female, Humans, Infusions, Intravenous, Male, Maximum Tolerated Dose, Middle Aged, Recurrence, Antineoplastic Agents administration & dosage, Multiple Myeloma drug therapy, Tetrahydroisoquinolines administration & dosage
- Published
- 2016
- Full Text
- View/download PDF
9. Phase II clinical trial for the evaluation of bortezomib within the reduced intensity conditioning regimen (RIC) and post-allogeneic transplantation for high-risk myeloma patients.
- Author
-
Caballero-Velázquez T, López-Corral L, Encinas C, Castilla-Llorente C, Martino R, Rosiñol L, Sampol A, Caballero D, Serrano D, Heras I, San Miguel J, and Pérez-Simón JA
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Apoptosis drug effects, Boronic Acids administration & dosage, Boronic Acids adverse effects, Boronic Acids pharmacology, Bortezomib, Chemical and Drug Induced Liver Injury etiology, Combined Modality Therapy, Cyclosporine therapeutic use, Drug Synergism, Female, Graft vs Host Disease epidemiology, Hematologic Diseases chemically induced, Humans, Immunosuppressive Agents administration & dosage, Immunosuppressive Agents adverse effects, Immunosuppressive Agents pharmacology, Immunosuppressive Agents therapeutic use, Maintenance Chemotherapy, Male, Melphalan administration & dosage, Melphalan therapeutic use, Middle Aged, Multiple Myeloma drug therapy, Peripheral Nervous System Diseases chemically induced, Protease Inhibitors administration & dosage, Protease Inhibitors adverse effects, Protease Inhibitors pharmacology, Pyrazines administration & dosage, Pyrazines adverse effects, Pyrazines pharmacology, Remission Induction, Reoperation, Salvage Therapy, T-Lymphocyte Subsets drug effects, Transplantation, Autologous, Transplantation, Homologous, Vidarabine administration & dosage, Vidarabine analogs & derivatives, Vidarabine therapeutic use, Boronic Acids therapeutic use, Multiple Myeloma surgery, Peripheral Blood Stem Cell Transplantation, Protease Inhibitors therapeutic use, Pyrazines therapeutic use, Transplantation Conditioning methods
- Abstract
The current study was designed to assess the safety and efficacy of bortezomib in combination with fludarabine and melphalan as reduced intensity conditioning before allogeneic stem cell transplantation in patients with high risk multiple myeloma. Sixteen patients were evaluable. The median number of previous line of treatment was 3; all patients had relapsed following a prior autograft and 13 had previously received bortezomib. Fifteen of them either remained stable or improved disease status at day +100 post-transplant, including 11 patients with active disease. More specifically, nine patients (56%) and five patients (31%) reached complete remission and partial response, respectively. 25% developed grade III acute graft-versus-host disease. The cumulative incidence of non-relapse mortality, relapse and overall survival were 25%, 54% and 41%, respectively, at 3 years. Regarding the non-haematological toxicity (grade>2), two patients developed peripheral neuropathy, two patients liver toxicity and 1 pulmonary toxicity early post-transplant. The haematological toxicity was only observed during the first three cycles mostly related to low haemoglobin and platelet levels. The current trial is the first one evaluating the safety and efficacy of bortezomib as part of a reduced intensity conditioning regimen among patients with high risk multiple myeloma., (© 2013 John Wiley & Sons Ltd.)
- Published
- 2013
- Full Text
- View/download PDF
10. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline.
- Author
-
Richardson PG, Sonneveld P, Schuster MW, Stadtmauer EA, Facon T, Harousseau JL, Ben-Yehuda D, Lonial S, Goldschmidt H, Reece D, Bladé J, Boccadoro M, Cavenagh JD, Boral AL, Esseltine DL, Wen PY, Amato AA, Anderson KC, and San Miguel J
- Subjects
- Aged, Antineoplastic Agents adverse effects, Boronic Acids adverse effects, Bortezomib, Clinical Protocols, Drug Administration Schedule, Female, Follow-Up Studies, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multiple Myeloma complications, Multiple Myeloma mortality, Peripheral Nervous System Diseases chemically induced, Peripheral Nervous System Diseases diagnosis, Pyrazines adverse effects, Recurrence, Statistics, Nonparametric, Survival Rate, Antineoplastic Agents therapeutic use, Boronic Acids therapeutic use, Multiple Myeloma drug therapy, Peripheral Nervous System Diseases drug therapy, Pyrazines therapeutic use
- Abstract
The frequency, characteristics and reversibility of bortezomib-associated peripheral neuropathy were evaluated in the phase III APEX (Assessment of Proteasome Inhibition for Extending Remissions) trial in patients with relapsed myeloma, and the impact of a dose-modification guideline on peripheral neuropathy severity and reversibility was assessed. Patients received bortezomib 1.3 mg/m(2) (days 1, 4, 8, 11, eight 21-d cycles, then days 1, 8, 15, 22, three 35-d cycles); bortezomib was held, dose-reduced or discontinued depending on peripheral neuropathy severity, according to a protocol-specified dose-modification guideline. Overall, 124/331 patients (37%) had treatment-emergent peripheral neuropathy, including 30 (9%) with grade >or=3; incidence and severity were not affected by age, number/type of prior therapies, baseline glycosylated haemoglobin level, or diabetes history. Grade >or=3 incidence appeared lower versus phase II trials (13%) that did not specifically provide dose-modification guidelines. Of patients with grade >or=2 peripheral neuropathy, 58/91 (64%) experienced improvement or resolution to baseline at a median of 110 d, including 49/72 (68%) who had dose modification versus 9/19 (47%) who did not. Efficacy did not appear adversely affected by dose modification for grade >or=2 peripheral neuropathy. Bortezomib-associated peripheral neuropathy is manageable and reversible in most patients with relapsed myeloma. Dose modification using a specific guideline improves peripheral neuropathy management without adversely affecting outcome.
- Published
- 2009
- Full Text
- View/download PDF
11. Characterisation of haematological profiles and low risk of thromboembolic events with bortezomib in patients with relapsed multiple myeloma.
- Author
-
Lonial S, Richardson PG, San Miguel J, Sonneveld P, Schuster MW, Bladé J, Cavenagh J, Rajkumar SV, Jakubowiak AJ, Esseltine DL, Anderson KC, and Harousseau JL
- Subjects
- Bortezomib, Clinical Trials as Topic, Dexamethasone therapeutic use, Drug Therapy, Combination, Erythropoietin therapeutic use, Female, Humans, Immunosuppressive Agents therapeutic use, Logistic Models, Male, Middle Aged, Multiple Myeloma blood, Pulmonary Embolism complications, Recombinant Proteins, Recurrence, Risk, Treatment Outcome, Venous Thrombosis complications, Boronic Acids therapeutic use, Multiple Myeloma drug therapy, Protease Inhibitors therapeutic use, Pyrazines therapeutic use
- Abstract
Haematological toxicities and thromboembolic (TE) events are common complications of myeloma therapy. TE risk may be elevated with combination regimens, notably thalidomide/lenalidomide plus high-dose dexamethasone; concomitant erythropoietin appears to further increase the risk with lenalidomide-dexamethasone. We characterised thrombocytopenia and neutropenia in the phase 3 APEX (Assessment of Proteasome Inhibition for Extending Remissions) study of bortezomib versus high-dose dexamethasone in relapsed myeloma, and calculated the incidences of deep-vein thrombosis (DVT)/pulmonary embolism (PE) with: bortezomib or dexamethasone +/- erythropoietin in APEX; bortezomib +/- dexamethasone +/- erythropoietin in two phase 2 studies of relapsed/refractory myeloma. Bortezomib-associated thrombocytopenia and neutropenia were transient, predictable and manageable; mean platelet and neutrophil counts followed a cyclical pattern, and improved over the treatment course. Grade 3/4 thrombocytopenia incidence was higher with bortezomib versus dexamethasone (26%/4% vs. 5%/1%), but significant bleeding events were comparable (4% vs. 5%). DVT/PE incidence was low (< or =3.1%) in all analyses; addition of dexamethasone/erythropoietin did not affect TE risk. In APEX, TE risk appeared lower with bortezomib versus dexamethasone. Bortezomib caused transient and cyclical thrombocytopenia and was not associated with elevated TE risk, alone or with dexamethasone +/- erythropoietin. Preliminary data suggest bortezomib may reduce the thrombogenic potential of combination regimens via inhibition of platelet function or other mechanism-specific effects on coagulation.
- Published
- 2008
- Full Text
- View/download PDF
12. Low expression of ZHX2, but not RCBTB2 or RAN, is associated with poor outcome in multiple myeloma.
- Author
-
Armellini A, Sarasquete ME, García-Sanz R, Chillón MC, Balanzategui A, Alcoceba M, Fuertes M, López R, Hernández JM, Fernández-Calvo J, Sierra M, Megido M, Orfão A, Gutiérrez NC, González M, and San Miguel JF
- Subjects
- Age Factors, Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Biomarkers, Tumor genetics, Bone Marrow Cells metabolism, Female, Gene Expression, Gene Expression Profiling methods, Homeodomain Proteins genetics, Humans, Male, Middle Aged, Multiple Myeloma drug therapy, Neoplasm Proteins genetics, Paraproteinemias drug therapy, Paraproteinemias metabolism, Plasma Cells metabolism, Prognosis, Reverse Transcriptase Polymerase Chain Reaction methods, Transcription Factors genetics, Treatment Outcome, ran GTP-Binding Protein genetics, ran GTP-Binding Protein metabolism, Biomarkers, Tumor metabolism, Homeodomain Proteins metabolism, Multiple Myeloma metabolism, Neoplasm Proteins metabolism, Transcription Factors metabolism
- Abstract
RAN, ZHX2 and RCBTB2 (CHC1L) expression was evaluated by quantitative real time reverse transcription polymerase chain reaction in plasma cells from 85 monoclonal gammopathies: 58 symptomatic multiple myeloma (MM) (52 untreated, six relapsed), eight smouldering MM, five monoclonal gammopathy of undetermined significance, four plasma cell leukaemias and 10 myeloid cell lines. ZHX2 was weakly expressed in high-risk/proliferative disease compared to low-risk or indolent disease. High ZHX2 expression was associated with better response and longer survival after high-dose therapy. RCBTB2 expression was weaker in hyperdiploid versus non-hyperdiploid cases while RAN was more expressed in symptomatic MM and cell lines.
- Published
- 2008
- Full Text
- View/download PDF
13. Should prophylactic granulocyte-colony stimulating factor be used in multiple myeloma patients developing neutropenia under lenalidomide-based therapy?
- Author
-
Mateos MV, García-Sanz R, Colado E, Olazábal J, and San-Miguel J
- Subjects
- Aged, Antineoplastic Agents therapeutic use, Clinical Trials as Topic, Dexamethasone therapeutic use, Drug Administration Schedule, Drug Therapy, Combination, Female, Humans, Lenalidomide, Male, Middle Aged, Multiple Myeloma complications, Neutropenia complications, Neutropenia drug therapy, Recombinant Proteins, Thalidomide adverse effects, Thalidomide therapeutic use, Treatment Outcome, Antineoplastic Agents adverse effects, Granulocyte Colony-Stimulating Factor therapeutic use, Multiple Myeloma drug therapy, Neutropenia chemically induced, Thalidomide analogs & derivatives
- Abstract
Lenalidomide combined with dexamethasone has significant clinical activity in the treatment of multiple myeloma (MM). In previous clinical trials lenalidomide-induced neutropenia was a frequent side-effect, often leading to treatment delays and dose reductions. We describe three MM patients treated with lenalidomide plus dexamethasone, which developed grade 3/4 neutropenia during the initial cycles, but without serious infection. Administration of granulocyte-colony stimulating factor (G-CSF) for 3 d prevented further neutropenia, treatment delays, dose reductions, or infectious complications during the following cycles. Consequently, G-CSF could be effective in preventing further neutropenia-related complications without compromising treatment efficacy in MM patients with lenalidomide-induced neutropenia.
- Published
- 2008
- Full Text
- View/download PDF
14. Randomized comparison of dexamethasone combined with melphalan versus melphalan with prednisone in the treatment of elderly patients with multiple myeloma.
- Author
-
Hernández JM, García-Sanz R, Golvano E, Bladé J, Fernandez-Calvo J, Trujillo J, Soler JA, Gardella S, Carbonell F, Mateo G, and San Miguel JF
- Subjects
- Aged, Aged, 80 and over, Dexamethasone administration & dosage, Female, Follow-Up Studies, Humans, Male, Melphalan administration & dosage, Middle Aged, Multiple Myeloma mortality, Prednisone administration & dosage, Regression Analysis, Survival Rate, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy
- Abstract
Melphalan-prednisone (MP) has been the gold standard treatment for more than 30 years in elderly multiple myeloma (MM) patients. In order to assess whether the combination of dexamethasone with melphalan (MD) could improve on the efficacy of MP, we have carried out a randomized trial comparing both treatment approaches. A total of 201 patients >/=70 years old were included in the study. The overall response rate was similar after six cycles (MP: 67.9%versus MD: 64.5%) and after 12 cycles (MP: 49.4%versus MD: 46.1%). However, the proportion of complete responses (CR) was higher in the MD arm, particularly after 12 cycles (MD: 22.4%versus MP: 9.1%; P < 0.05). There was no significant difference in event-free survival (MP: 15.9 months versus MD: 23.3 months). The median overall survival in both arms was almost identical (MP: 29.4 months versus MD: 27.2 months; P = 0.63). No significant differences in haematological toxicity were observed, but non-haematological toxicity was significantly higher in the MD arm. According to these results MP remains as the gold standard for treatment of MM and should be the reference for comparison of new therapeutic approaches involving novel agents.
- Published
- 2004
- Full Text
- View/download PDF
15. Tandem transplants with different high-dose regimens improve the complete remission rates in multiple myeloma. Results of a Grupo Español de Síndromes Linfoproliferativos/Trasplante Autólogo de Médula Osea phase II trial.
- Author
-
Lahuerta JJ, Grande C, Martínez-Lopez J, De La Serna J, Toscano R, Ortiz MC, Larregla S, Conde E, Insunza A, Gonzalez-San Miguel JD, Bargay J, Cabrera R, García-Ruiz JC, Albó C, García-Alonso L, Solano F, Vivancos P, León A, and San Miguel J
- Subjects
- Disease-Free Survival, Female, Follow-Up Studies, Humans, Male, Middle Aged, Multiple Myeloma mortality, Prospective Studies, Reoperation, Survival Analysis, Transplantation Conditioning methods, Transplantation, Autologous, Treatment Outcome, Multiple Myeloma surgery, Stem Cell Transplantation methods
- Abstract
Between 1994 and 1999, 88 multiple myeloma (MM) patients were included in a phase II study to evaluate a tandem autologous stem cell transplantation (ASCT) programme. The first was conditioned with melphalan 200 mg/m2 (MEL200-ASCT1), and the second with cyclophosphamide, etoposide and BCNU (CBV-ASCT2). All patients were in response after MEL200-ASCT1. A control group of MM patients with response to a single ASCT was selected to compare outcomes. After MEL200-ASCT1, 26 patients (30%) achieved complete remission (CR). Of the remaining 48 evaluable patients, 16 (33%) achieved CR with CBV-ASCT2. The final CR rate was 48%. The 5-year survival (OS) was 55%[95% confidence interval (CI) 43-67%] while the event-free survival (EFS) was 28% (95% CI 15-39%). CR status after CBV-ASCT2 was the most important prognostic factor for OS and EFS (P = 0.00001), although no differences in outcomes were detected when the patients in CR after MEL200-ASCT1 were compared with those who obtained CR after CBV-ASCT2. Univariate and multivariate analyses showed improved OS and EFS for the tandem series as compared with the control series treated with a single MEL200-ASCT. However, in a stratified comparison by response, there were no prognostic differences between tandem patients and control patients treated with a single ASCT. In summary, our study suggests that the benefit of a second high-dose therapy course depends on its capacity to result in CR for MM patients who have not attained CR after ASCT1.
- Published
- 2003
- Full Text
- View/download PDF
16. Thalidomide in combination with cyclophosphamide and dexamethasone (thacydex) is effective in soft-tissue plasmacytomas.
- Author
-
González-Porras JR, González M, García-Sanz R, and San Miguel JF
- Subjects
- Aged, Clavicle, Cyclophosphamide administration & dosage, Dexamethasone administration & dosage, Drug Resistance, Neoplasm, Humans, Male, Middle Aged, Recurrence, Thalidomide administration & dosage, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Multiple Myeloma drug therapy, Skin Neoplasms drug therapy, Soft Tissue Neoplasms drug therapy
- Published
- 2002
- Full Text
- View/download PDF
17. Remission status defined by immunofixation vs. electrophoresis after autologous transplantation has a major impact on the outcome of multiple myeloma patients.
- Author
-
Lahuerta JJ, Martinez-Lopez J, Serna JD, Bladé J, Grande C, Alegre A, Vazquez L, García-Laraña J, Sureda A, Rubia JD, Conde E, Martinez R, Perez-Equiza K, Moraleda JM, León A, Besalduch J, Cabrera R, Miguel JD, Morales A, García-Ruíz JC, Diaz-Mediavilla J, and San-Miguel J
- Subjects
- Electrophoresis, Female, Humans, Male, Middle Aged, Multiple Myeloma drug therapy, Multiple Myeloma mortality, Multivariate Analysis, Paraproteins urine, Precipitin Tests, Prognosis, Proportional Hazards Models, Regression Analysis, Retrospective Studies, Survival Analysis, Transplantation, Autologous, Treatment Outcome, Hematopoietic Stem Cell Transplantation, Multiple Myeloma surgery
- Abstract
We have retrospectively analysed 344 multiple myeloma (MM) patients (202 de novo patients) treated in a non-uniform way in whom high-dose therapy and autologous stem cell transplantation (ASCT) response was simultaneously measured by both electrophoresis (EP) and immunofixation (IF). Patients in complete remission (CR) by EP were further subclassified as CR1 when IF was negative and CR2 when it remained positive. Partial responders (PR) were also subclassified as PR1 (very good PR, > 90% reduction in M-component) or PR2 (50-90% reduction). CR1 patients showed a significantly better event-free survival (EFS) [35% at 5 years, 95% confidence interval (CI) 17-53, median 46 months] and overall survival (OS) (72% at 5 years, CI 57-86, median not reached) compared with any other response group (univariate comparison P < 0.00000 to P = 0. 004). In contrast, comparison of CR2 with PR1 and with PR2 did not define different prognostic subgroups (median EFS 30, 30 and 26 months respectively, P = 0.6; median survival 56, 44 and 42 months respectively, P = 0.5). The non-responding patients had the worst outcome (5-year OS 8%, median 7 months). Multivariate analysis confirmed both the absence of differences among CR2, PR1 and PR2 and the highly discriminatory prognostic capacity of a three-category classification: (i) CR1 (ii) CR2 + PR1 + PR2, and (iii) non-response (EFS P < 0.00000; OS P < 0.00000; both Cox models P < 0.00000). In the logistic regression analysis, the factors significantly associated with failure to achieve CR1 were the use of two or more up-front chemotherapy lines, status of non-response pre-ASCT and inclusion of total body irradiation (TBI) in the preparative regimen. Tandem transplants or the use of multiple agents (busulphan and melphalan) in the preparative regimen resulted in a higher CR1 level; none of the biological factors explored influenced the possibility of achieving CR1. These results confirm that, in MM patients undergoing ASCT, achieving a negative IF identifies the patient subset with the best prognosis; accordingly, therapeutic strategies should be specifically designed to achieve negative IF.
- Published
- 2000
- Full Text
- View/download PDF
18. High-sensitive immunophenotyping and DNA ploidy studies for the investigation of minimal residual disease in multiple myeloma.
- Author
-
Almeida J, Orfao A, Ocqueteau M, Mateo G, Corral M, Caballero MD, Blade J, Moro MJ, Hernandez J, and San Miguel JF
- Subjects
- Bone Marrow Transplantation, DNA analysis, Female, Flow Cytometry, Humans, Leukapheresis, Male, Middle Aged, Neoplasm, Residual, Phenotype, Sensitivity and Specificity, Immunophenotyping methods, Multiple Myeloma diagnosis, Ploidies
- Abstract
Sensitive techniques for monitoring minimal residual disease (MRD) in multiple myeloma (MM) are needed to evaluate the effectiveness of new intensive treatment strategies. The aim of the present study was to explore the applicability and sensitivity of flow cytometry immunophenotyping and DNA ploidy studies for the investigation of residual myelomatous plasma cells (PC) in MM patients. Bone marrow (BM) samples from 61 untreated MM patients were immunophenotypically analysed with a panel of 21 monoclonal antibodies, using a high-sensitive method based on a two-step acquisition procedure through a SSC/CD38 -CD138+ 'live-gate'. Overall, in 87% of MM cases, PC displayed an aberrant phenotype at diagnosis. The most important aberrant criteria were: antigen over-expression of CD56 (62%), CD28 (16%) and CD33 (6%) and asynchronous expression of CD117 (28%), sIg (21%) and CD20 (10%). DNA aneuploidy was found in 62% of cases. The simultaneous use of these two techniques allowed the detection of aberrant/aneuploid PC in 95% of the cases. Based on dilutional experiments, the detection limit of both techniques ranged from 10(-4) to 10(-5). In 29 stem cells harvests and 19 BM samples obtained 3 months after autologous transplantation, we have investigated the presence of residual myelomatous PC; they were detected in 44% of the stem cell collections and in 61% of the BM samples obtained after transplant. The percentage of pathological PC did not significantly change during the days of harvest. In summary, the present study shows that the combined use of immunophenotyping and DNA ploidy studies is a suitable approach for MRD investigation in MM patients based on their applicability (95% of cases) and sensitivity (up to 10(-5)).
- Published
- 1999
- Full Text
- View/download PDF
19. IL-4 improves the detection of cytogenetic abnormalities in multiple myeloma and increases the proportion of clonally abnormal metaphases.
- Author
-
Hernández JM, Gutiérrez NC, Almeida J, García JL, Sánchez MA, Mateo G, Ríos A, and San Miguel JF
- Subjects
- Aged, Aged, 80 and over, Bone Marrow Cells pathology, DNA, Neoplasm analysis, Drug Combinations, Flow Cytometry, Granulocyte-Macrophage Colony-Stimulating Factor pharmacology, Humans, Interleukin-6 pharmacology, Karyotyping, Middle Aged, Mitosis physiology, Ploidies, Tumor Cells, Cultured, Interleukin-4 pharmacology, Metaphase physiology, Multiple Myeloma pathology
- Abstract
In the present study the incidence of abnormal karyotypes and the number and proportion of abnormal metaphases obtained in multiple myeloma (MM) using three culture conditions were compared: unstimulated culture (72 h), IL-6/GM-CSF-stimulated culture (120 h) and IL-4-stimulated culture (120 h). The three types of culture conditions were assessed simultaneously on bone marrow samples from 30 consecutive myeloma patients. In addition DNA content (DNA ploidy and cell cycle) was analysed by flow cytometry. The number of MM samples with clonal karyotypic abnormalities was higher after IL-4-stimulated cultures (53%) than it was after IL-6 + GM-CSF (37%) and unstimulated (30%) cultures. The benefit of IL-4 was also observed in cases with low numbers of plasma cells in the bone marrow, in early clinical stages and in untreated patients. In those cases in whom clonal chromosomal abnormalities were detected by the three culture methods. the cytogenetic findings were always identical. According to our results the addition of IL-4 to the cultures of bone marrow cells in MM increases the number of abnormal metaphases.
- Published
- 1998
- Full Text
- View/download PDF
20. Expression of the CD117 antigen (c-Kit) on normal and myelomatous plasma cells.
- Author
-
Ocqueteau M, Orfao A, García-Sanz R, Almeida J, Gonzalez M, and San Miguel JF
- Subjects
- Adult, Aged, Aged, 80 and over, Aneuploidy, Cell Differentiation, Female, Flow Cytometry, Humans, Immunophenotyping, Male, Middle Aged, Multiple Myeloma pathology, Prognosis, Multiple Myeloma metabolism, Plasma Cells metabolism, Proto-Oncogene Proteins c-kit metabolism
- Abstract
The surface expression of CD117 on plasma cells (PCs) from normal individuals and patients with multiple myeloma (MM) has been analysed using triple-stained cells for flow cytometry. In addition, the clinical significance of CD117 expression in MM patients and its possible value for the evaluation of minimal residual disease was explored. A total of 11 healthy volunteers and 56 untreated MM patients were included in the study. The expression of CD117 was analysed by flow cytometry, using simultaneous staining with the MAbs BB4, CD117 and CD38. Cell acquisition was performed in two consecutive steps using a live gate drawn on SSC/CD38 cells and a total of 300,000 events were acquired. For data analysis, the Paint-a-Gate Plus software (Becton Dickinson) was used. PCs were identified according to their strong reactivity for CD38 and their positivity for BB4, as well as by their light scatter distribution. Dilution experiments of CD117+ myelomatous PCs with normal bone marrow (BM) cells were performed in order to assess the sensitivity level of the technique for detection of CD117+ residual PCs. None of the PCs from normal BM samples showed reactivity for the CD117 antigen. In contrast, CD117 antigen was present in 18/56 MM patients (32%), the proportion of positive cells in these cases being as high as 92.1 +/- 9%. Therefore, within PC lineage the c-Kit antigen would be restricted to the myelomatous population and thus could be considered as a 'tumour-associated marker' for monitoring minimal residual disease in about one third of MM patients. Dilution experiments indicate that the detection limit with this marker would be 10(-4) (one myelomatous PC/10(4) normal BM cells). Upon comparing the clinical and haematological disease characteristics of CD117-positive and CD117-negative cases, no significant differences were found.
- Published
- 1996
- Full Text
- View/download PDF
21. Cytokine therapy in multiple myeloma.
- Author
-
Peest D, Bladé J, Harousseau JL, Klein B, Osterborg A, and San Miguel JF
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Humans, Interferon-alpha administration & dosage, Interferon-alpha therapeutic use, Remission Induction, Tumor Cells, Cultured, Cytokines therapeutic use, Multiple Myeloma therapy
- Published
- 1996
- Full Text
- View/download PDF
22. Analysis of natural killer-associated antigens in peripheral blood and bone marrow of multiple myeloma patients and prognostic implications.
- Author
-
García-Sanz R, González M, Orfão A, Moro MJ, Hernández JM, Borrego D, Carnero M, Casanova F, Bárez A, Jiménez R, Portero JA, and San Miguel JF
- Subjects
- Adult, Aged, Aged, 80 and over, Antigens, CD blood, CD3 Complex analysis, CD3 Complex blood, CD56 Antigen analysis, CD56 Antigen blood, CD57 Antigens analysis, CD57 Antigens blood, Female, Humans, Immunophenotyping, Lymphocytes immunology, Male, Middle Aged, Prognosis, Receptors, IgG analysis, Antigens, CD analysis, Bone Marrow immunology, Killer Cells, Natural immunology, Multiple Myeloma immunology
- Abstract
The aim of this study was to analyse the expression of NK-associated antigens in both peripheral blood and bone marrow lymphocytes from a large series of newly diagnosed multiple myeloma patients. 112 patients with untreated multiple myeloma (MM) were included in the study. 36 sex- and age-matched healthy volunteers were used as controls for peripheral blood (PB) studies and 14 for the bone marrow (BM) studies. Simultaneous stainings with the CD3/CD56, CD2/CD16 and CD8/CD57 monoclonal antibodies were systematically performed in PB and CD3/CD56 and CD2/CD16 in BM in order to analyse their relationship with the clinical and biological characteristics of the disease and survival. The expression of NK-associated antigens (CD56, CD16 and CD57) assessed within the lymphoid gate, was significantly increased (P < 0.001) in the PB of MM patients both in relative and absolute numbers. In the BM a significant increase in the percentage of CD56+ lymphocytes (P < 0.001) was also observed; in contrast, the proportion of CD16+ cells did not differ significantly from that of normal BM samples. The number of CD56+CD3- lymphocytes increased significantly within high-risk patients (869 +/- 671) as compared to intermediate (388 +/- 212) and low-risk patients (274 +/- 199) (P = 0.04). Moreover, patients with high values of CD56+CD3- lymphocytes showed a statistically significant association with several adverse prognostic factors including anaemia, hypoalbuminaemia, renal failure, high beta 2M, DNA diploidy and high S-phase plasma cells. In addition, patients with higher absolute numbers of PB CD56+CD3-lymphocytes displayed a poorer prognosis, whereas patients with higher values of CD57+CD8- cells had a better outcome.
- Published
- 1996
- Full Text
- View/download PDF
23. Lymphoid subsets and prognostic factors in multiple myeloma. Cooperative Group for the Study of Monoclonal Gammopathies.
- Author
-
San Miguel JF, González M, Gascón A, Moro MJ, Hernández JM, Ortega F, Jiménez R, Guerras L, Romero M, and Casanova F
- Subjects
- Age Factors, Aged, CD4-CD8 Ratio, Calcium blood, Creatinine blood, Female, Hemoglobins analysis, Humans, Male, Multiple Myeloma mortality, Plasma Cells pathology, Prognosis, Serum Albumin analysis, Urea blood, Multiple Myeloma blood, T-Lymphocyte Subsets pathology
- Abstract
In a uniform series of 170 untreated myeloma patients (MM) we investigated the distribution of T cell subsets in peripheral blood (PB) and their relationship with the most relevant disease characteristics, including survival. CD4 cells were significantly decreased both in percentage and absolute numbers (P less than 0.0001). On the other hand, the CD8 cells only showed a slight increase in relative numbers. Upon correlating the abnormalities in the distribution of T cells with other clinical and biological disease characteristics the most remarkable correlation was with survival. A low number of CD4 cells (less than 700 x 10(6)/l) was associated with both an advanced clinical stage and a shorter survival (20 v. 43 months, P = 0.01). Moreover, a significant correlation also exists between the decrease in CD4 cells and both high beta 2-microglobulin (beta 2M) levels and anaemia. On the other hand, no relationship was found with the type of M-component nor with the plasma cell phenotype. Finally multivariate analysis showed that the number of CD4 cells add independent prognostic information to other well-established tests for the assessment of disease outcome in patients with multiple myeloma.
- Published
- 1992
- Full Text
- View/download PDF
24. Immunophenotypic heterogeneity of multiple myeloma: influence on the biology and clinical course of the disease. Castellano-Leones (Spain) Cooperative Group for the Study of Monoclonal Gammopathies.
- Author
-
San Miguel JF, González M, Gascón A, Moro MJ, Hernández JM, Ortega F, Jimenez R, Guerras L, Romero M, and Casanova F
- Subjects
- Aged, Antigens, CD analysis, Antigens, CD20, Antigens, Differentiation analysis, Antigens, Differentiation, B-Lymphocyte analysis, Humans, Middle Aged, Multiple Myeloma mortality, Multiple Myeloma pathology, Neoplasm Staging, Neprilysin, Plasma Cells immunology, Antigens, Neoplasm analysis, Multiple Myeloma immunology
- Abstract
In 112 untreated myeloma patients we have analysed the immunophenotype of plasma cells both by immunofluorescence (IF) and immunocytochemistry (APAAP). Both techniques yielded similar results pointing to an important degree of heterogeneity in antigenic expression not only between different patients but also within the same patient. The expression of CD38 and Han-PC1 antigens (Ags) was almost constant (greater than 90% positive cases), while CD9 was detected in 66% of the cases. On the other hand, less than one third of patients were positive for CD10, CD20 and HLA-DR and generally with a weak expression (less than 30% positive plasma cells). In occasional cases plasma cells were weakly positive for the myelomonocytic markers CD13 (9%), CD15 (25%) and CD14 (6%). The possibility that this heterogeneity might be the result of different stages of differentiation of the neoplastic clone is suggested both by the positive correlation in the expression of some of these antigens (CD10, CD9, CD20, HLA-DR) and by the relationship between CD10 and myeloid antigens with immature plasma cell morphology. Finally, the cALLA antigen does not seem to be of significant value in predicting survival. Moreover, none of the other markers explored showed a clear influence in the course of the disease, although the tendency towards a lower survival found for the CD20+ cases as well as the association of the expression of some antigens and advanced clinical stage, may warrant further studies in a larger series of patients.
- Published
- 1991
- Full Text
- View/download PDF
25. Immunological phenotype of neoplasms involving the B cell in the last step of differentiation.
- Author
-
San Miguel JF, Caballero MD, Gonzalez M, Zola H, and Lopez Borrasca A
- Subjects
- Antibodies, Monoclonal, Bone Marrow pathology, Cell Differentiation, Humans, Phenotype, Plasma Cells immunology, B-Lymphocytes immunology, Multiple Myeloma immunology, Waldenstrom Macroglobulinemia immunology
- Abstract
The immunological phenotype of diseases involving the last step of B cell differentiation--multiple myeloma (MM, 38 patients) and Waldenström's macroglobulinaemia (WM, 12 patients)--was analysed with a panel of monoclonal antibodies (McAb) as well as conventional markers. Most of the bone marrow plasma cells (80%) from MM patients reacted with the McAb OKT10, FMC8 and FMC48. Plasma cells were consistently negative with FMC7, Leu-1 and mouse rosettes. Ia, B1 and SIg were expressed in a minority of plasma cells (less than 30%) in half of the cases. The circulating neoplastic cells from five MM patients showed a more immature phenotype, with a higher reactivity for OKIa, B1 and increased SIg and a lower expression of CIg, than bone marrow plasma cells. The malignant cells of WM patients differed from those of MM in the reactivity with FMC7, being positive in 10 out of 11 cases, and in their high expression of B1, Ia and SIg with a predominant mu+ phenotype. Mouse rosettes and Leu-1 were positive in one case; OKT10 was positive in three out of five WM patients studied. This phenotype indicates that WM cells correspond to an earlier stage of B cell differentiation than MM plasma cells. The McAb J5 was positive in three out of six MM and two out of four WM analysed. The antigenic differences observed in MM and WM patients support the notion that the cells of the neoplastic clone are able to undergo a certain degree of differentiation.
- Published
- 1986
- Full Text
- View/download PDF
26. Plasmablastic multiple myeloma: an immunologically different subtype.
- Author
-
San Miguel JF, Moro MJ, and Gonzalez M
- Subjects
- Humans, Phenotype, Multiple Myeloma immunology, Plasma Cells immunology
- Published
- 1987
- Full Text
- View/download PDF
27. Randomized comparison of dexamethasone combined with melphalanversusmelphalan with prednisone in the treatment of elderly patients with multiple myeloma.
- Author
-
Hernández, J. M., García-Sanz, R., Golvano, E., Bladé, J., Fernandez-Calvo, J., Trujillo, J., Soler, J. A., Gardella, S., Carbonell, F., Mateo, G., and San Miguel, J. F.
- Subjects
MULTIPLE myeloma ,PREDNISONE ,THERAPEUTICS ,DRUG efficacy ,PATIENTS ,GOLD standard - Abstract
Melphalan–prednisone (MP) has been the gold standard treatment for more than 30 years in elderly multiple myeloma (MM) patients. In order to assess whether the combination of dexamethasone with melphalan (MD) could improve on the efficacy of MP, we have carried out a randomized trial comparing both treatment approaches. A total of 201 patients≥70 years old were included in the study. The overall response rate was similar after six cycles (MP: 67·9%versusMD: 64·5%) and after 12 cycles (MP: 49·4%versusMD: 46·1%). However, the proportion of complete responses (CR) was higher in the MD arm, particularly after 12 cycles (MD: 22·4%versusMP: 9·1%;P < 0·05). There was no significant difference in event-free survival (MP: 15·9 monthsversusMD: 23·3 months). The median overall survival in both arms was almost identical (MP: 29·4 monthsversusMD: 27·2 months;P = 0·63). No significant differences in haematological toxicity were observed, but non-haematological toxicity was significantly higher in the MD arm. According to these results MP remains as the gold standard for treatment of MM and should be the reference for comparison of new therapeutic approaches involving novel agents. [ABSTRACT FROM AUTHOR]
- Published
- 2004
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.