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1.
Hematol Oncol ; 40(5): 1009-1019, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35638723

RESUMEN

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.


Asunto(s)
Mieloma Múltiple , Humanos , Lenalidomida , Mieloma Múltiple/tratamiento farmacológico , Terapia Recuperativa , Estudios Retrospectivos , Dexametasona/efectos adversos
2.
Eur J Haematol ; 108(3): 178-189, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34716957

RESUMEN

The lack of a randomized trial comparing carfilzomib (K) versus elotuzumab (Elo) associated with lenalidomide and dexamethasone (Rd) prompted us to assess the relative usefulness of one triplet over the other. Five independent retrospective cohorts of 883 relapsed/refractory multiple myeloma (RRMM) patients, including 300 EloRd and 583 KRd cases, outside clinical trials, entered this non-randomized comparison. KRd cohort accounted for a higher incidence of younger patients, cases with ≥3 lines of therapy, already exposed to lenalidomide, International Staging System (ISS) stage III, and abnormal lactic dehydrogenase (LDH) level compared with EloRd cohort. Moreover, cytogenetic risk categories, detected in roughly one-third of cases, were equally distributed between the two therapy arms. The probability of CR+VGPR response was significantly higher in KRd (n = 314, 53.9%) than in EloRd patients (n = 111, 37.0%). Likewise, the cumulative incidence function of CR+VGPR, taking into account the competitive risk of death, was significantly higher in KRd arm patients than those in the EloRd arm (p = .003). Moreover, KRd treatment significantly reduced the progression or death risk by 46% in an adjusted multivariate analysis (HR: 0.54, 95% CI 0.42-0.69, p < .0001). Finally, in an adjusted illness-progression/death model, the effect of KRd versus EloRd was of higher magnitude among those who achieved CR+VGPR (-39% hazard ratio reduction, p = .02) than among those who achieved < VGPR (-29% hazard ratio reduction, p = .007). With limitations characteristic to any retrospective analysis, this current clinical practice study's overall results demonstrated potential benefits of KRd therapy compared with EloRd. This observation may help the daily clinical practice.


Asunto(s)
Mieloma Múltiple , Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona , Humanos , Lenalidomida , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/tratamiento farmacológico , Oligopéptidos , Estudios Retrospectivos , Terapia Recuperativa
3.
Ann Hematol ; 100(2): 429-436, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33161453

RESUMEN

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.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Dexametasona/administración & dosificación , Dexametasona/efectos adversos , Supervivencia sin Enfermedad , Femenino , Humanos , Lenalidomida/administración & dosificación , Lenalidomida/efectos adversos , Masculino , Persona de Mediana Edad , Oligopéptidos/administración & dosificación , Oligopéptidos/efectos adversos , Recurrencia , Tasa de Supervivencia
4.
Ann Hematol ; 98(6): 1449-1455, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30868307

RESUMEN

This study reports a retrospective multicenter experience by the Rete Ematologica Pugliese (REP) over the past 16 years, aiming to compare the patients characteristics and outcomes of 21 brentuximab vedotin (BV)-pre-treated patients to 51 patients who received reduced-intensity conditioning (RIC) allogeneic stem cell transplantation (SCT) without prior BV. In total, 72 patients with classical Hodgkin's lymphomas who received allogeneic SCT were retrospectively studied. Prior use of BV had no effect on either engraftment or the incidence and severity of acute graft versus host disease (GVHD). Indeed, a lower incidence of chronic GVHD was observed in the BV group, with a 43% cumulative incidence at 3 years versus 47% in the no BV group, although this was not statistically significant. Despite the low incidence of chronic GVHD, survival was not worse in the BV-treated group: 3-year progression-free survival (PFS) was 53%, 3-year overall survival (OS) was 62%, 3-year non-relapse mortality (NRM) was 24%. In the no BV group, the 3-year PFS was 33%, 3-year OS was 44%, and 3-year NRM was 14%. In chemorefractory patients at the time of transplant, we found a statistically significant difference in PFS between the BV and no BV groups (51% vs. 10%, p = 0.013).


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin/terapia , Inmunoconjugados/uso terapéutico , Adolescente , Adulto , Antineoplásicos Inmunológicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trasplante de Médula Ósea , Brentuximab Vedotina , Terapia Combinada , Resistencia a Antineoplásicos , Femenino , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Enfermedad de Hodgkin/tratamiento farmacológico , Enfermedad de Hodgkin/mortalidad , Humanos , Inmunoconjugados/administración & dosificación , Masculino , Persona de Mediana Edad , Trasplante de Células Madre de Sangre Periférica , Premedicación , Supervivencia sin Progresión , Estudios Retrospectivos , Terapia Recuperativa , Acondicionamiento Pretrasplante/métodos , Trasplante Homólogo , Resultado del Tratamiento , Adulto Joven
6.
Ann Hematol ; 97(10): 1817-1824, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30054707

RESUMEN

Brentuximab vedotin (BV) shows a high overall response rate (ORR) in relapsed/refractory (R/R) Hodgkin lymphoma (HL) after autologous transplant (ASCT). The aim of this multicenter study, conducted in nine Hematology Departments of Rete Ematologica Pugliese, was to retrospectively evaluate the efficacy and safety of BV as salvage therapy and as bridge regimen to ASCT or allogeneic transplant (alloSCT) in R/R HL patients. Seventy patients received BV. Forty-five patients (64%) were treated with BV as bridge to transplant:16 (23%) patients as bridge to ASCT and 29 (41%) as bridge to alloSCT. Twenty-five patients (36%), not eligible for transplant, received BV as salvage treatment. The ORR was 59% (CR 26%). The ORR in transplant naïve patients was 75% (CR 31%). In patients treated with BV as bridge to alloSCT, the ORR was 62% (CR 24%). In a multivariate analysis, the ORR was lower in refractory patients (p < 0.005). The 2y-OS was 70%. The median PFS was 17 months. Ten of the 16 (63%) naïve-transplant patients received ASCT, with 50% in CR before ASCT. In the 29 patients treated with BV as bridge to alloSCT, 28 (97%) proceeded to alloSCT with 25% in CR prior to alloSCT. The most common adverse events were peripheral neuropathy (50%), neutropenia (29%) and anemia (12%). These data suggest that BV is well tolerated and very effective in R/R HL, producing a substantial level of CR. BV may also be a key therapeutic agent to achieve good disease control before transplant, improving post- transplant outcomes, also in refractory and heavily pretreated patients, without significant overlapping toxicities with prior therapies.


Asunto(s)
Antineoplásicos/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Inmunoconjugados/uso terapéutico , Terapia Molecular Dirigida , Terapia Recuperativa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Brentuximab Vedotina , Terapia Combinada , Supervivencia sin Enfermedad , Evaluación de Medicamentos , Femenino , Enfermedades Hematológicas/inducido químicamente , Enfermedad de Hodgkin/radioterapia , Enfermedad de Hodgkin/terapia , Humanos , Inmunoconjugados/efectos adversos , Estimación de Kaplan-Meier , Antígeno Ki-1/inmunología , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Recurrencia , Inducción de Remisión , Estudios Retrospectivos , Trasplante de Células Madre , Trasplante Autólogo , Resultado del Tratamiento , Adulto Joven
7.
Br J Haematol ; 172(1): 111-21, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26458240

RESUMEN

High-dose chemotherapy (HDT) with autologous stem cell transplantation is the standard of care for relapsed/refractory (RR) Hodgkin lymphoma (HL). Given that HDT may cure a sizeable proportion of patients refractory to first salvage, development of newer conditioning regimens remains a priority. We present the results of a novel HDT regimen in which carmustine was substituted by a third-generation chloroethylnitrosourea, fotemustine, with improved pharmacokinetics and safety (FEAM; fotemustine, etoposide, cytarabine, melphalan) in 122 patients with RR-HL accrued into a prospective registry-based study. Application of FEAM resulted in a 2-year progression-free survival (PFS) of 73·8% [95% confidence interval (CI), 0·64-0·81] with median PFS, overall survival and time to progression yet to be reached. The 2-year risk of progression adjusted for the competitive risk of death was 19·4% (95% CI, 0·12-0·27) for the entire patient population. Most previously established independent risk factors, except for fluorodeoxyglucose ((18) (F) FDG)-uptake, were unable to predict for disease progression and survival after FEAM. Although 32% of patients had (18) (F) FDG-positrin emission tomography-positive lesions before HDT, the 2-year risk of progression adjusted for competitive risk of death was 19·4% (95% CI; 0·12-0·27). No unusual acute toxicities or early/late pulmonary adverse events were registered. FEAM emerges as an ideal HDT regimen for RR-HL patients typically pre-exposed to lung-damaging treatments.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Niño , Citarabina/administración & dosificación , Citarabina/efectos adversos , Evaluación de Medicamentos/métodos , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/terapia , Humanos , Estimación de Kaplan-Meier , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Compuestos de Nitrosourea/administración & dosificación , Compuestos de Nitrosourea/efectos adversos , Compuestos Organofosforados/administración & dosificación , Compuestos Organofosforados/efectos adversos , Tomografía de Emisión de Positrones , Estudios Prospectivos , Sistema de Registros , Terapia Recuperativa/efectos adversos , Terapia Recuperativa/métodos , Acondicionamiento Pretrasplante/métodos , Resultado del Tratamiento , Adulto Joven
8.
Front Oncol ; 12: 890376, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35924160

RESUMEN

The present study aimed to develop two survival risk scores (RS) for overall survival (OS, SRS KRd/EloRd ) and progression-free survival (PFS, PRS KRd/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 SRS KRd/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 PRS KRd/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, SRS KRd/EloRd and PRS KRd/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.

9.
Ann Hematol ; 90(12): 1449-56, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21437586

RESUMEN

In newly diagnosed multiple myeloma (MM), three/four-drug combinations as induction therapy seem to be more effective compared with two-drug associations in terms of response rate and duration of remission. Moreover, there is an emergent body of evidences that consolidation/maintenance therapy improves the quality of response and remission duration. However, the impact of these strategies in relapsed/refractory MM (r-rMM) is still unknown. This phase II study explored the four-drug combination of thalidomide, dexamethasone, pegylated liposomal doxorubicin (pLD), and bortezomib (ThaDD-V) as induction followed by consolidation therapy based on bortezomib-dexamethasone and thalidomide-dexamethasone and maintenance therapy with thalidomide in r-rMM patients. The primary end points of this study were best response and toxicity of the planned therapy. Forty-six patients were enrolled. At the end of therapy, the best response was as follows: 37% complete response (CR), 34.5% VGPR, and 4.5% PR with an ORR of 76%. Patients receiving ≤ 2 prior regimens had a CR rate significantly higher than those heavily treated (41% vs 0%; p=0.010). With a median follow-up of 31 months, median time to progression (TTP) and OS were 18.5 months and 40 months, respectively. By a 6-month landmark analysis, patients who completed the protocol had a significantly longer TTP compared with those who did not because of toxicity (not reached vs 7 months; p<0.0001). After the dose intensity of bortezomib was reduced due to an excess of peripheral neuropathy (PN), grade 3 PN occurred in 7.5% of patients. ThaDD-V followed by consolidation-maintenance therapy seems to be very effective in patients with r-rMM provided that this procedure is used early on relapse when very deep responses seem to be the rule.


Asunto(s)
Antineoplásicos/uso terapéutico , Ácidos Borónicos/uso terapéutico , Dexametasona/uso terapéutico , Doxorrubicina/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/prevención & control , Pirazinas/uso terapéutico , Talidomida/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bortezomib , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/fisiopatología , Recurrencia , Inducción de Remisión , Resultado del Tratamiento
10.
Br J Haematol ; 144(5): 653-9, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-19036082

RESUMEN

Maintenance therapy was explored in multiple myeloma (MM) patients after conventional thalidomide, dexamethasone and pegylated liposomal doxorubicin (ThaDD). Patients with newly or relapsed MM obtaining at least minor response after 6 ThaDD courses, were randomised to receive alpha-interferon (IFN) 3 MU 3 times a week or thalidomide 100 mg daily until relapse. Both groups also received pulsed dexamethasone 20 mg 4 d a month. Fifty-one patients were randomized in the IFN-dexamethasone (ID) arm and 52 in the thalidomide-dexamethasone (TD) arm. The characteristics of two groups were similar. A significantly better 2-years progression-free survival (PFS; 63% vs. 32%; P = 0.024) and overall survival (84% vs. 68%; P = 0.030) was observed in the thalidomide arm. In high-risk patients and in those achieving less than very good partial response after induction, TD fared better in term of PFS. Main side effects were peripheral neuropathy and constipation in TD group, fatigue, anorexia and haematological toxicity in ID arm. There was a 21% probability of discontinuation at 3 years in the thalidomide arm and 44% in the IFN arm (P = 0.014). Low-dose thalidomide plus pulsed low-dose dexamethasone after conventional thalidomide combination-based therapy was also feasible in the long term, enabling significantly better residual disease control if compared with a standard maintenance therapy.


Asunto(s)
Dexametasona/administración & dosificación , Inmunosupresores/uso terapéutico , Interferón-alfa/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Talidomida/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Dexametasona/uso terapéutico , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Estudios Prospectivos , Recurrencia , Inducción de Remisión , Estadísticas no Paramétricas , Tasa de Supervivencia , Talidomida/uso terapéutico
11.
Clin Lymphoma Myeloma Leuk ; 19(1): 35-40, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30293754

RESUMEN

BACKGROUND: Hodgkin lymphoma (HL) is a potentially curable disease, and modern therapy is expected to successfully cure more than 80% of the patients. However, patients progressing after intensive treatments, such as autologous stem cell transplantation (SCT), have a very poor outcome. Allogeneic SCT offers the only strategy with a curative potential for these patients. This study reports a retrospective multicenter experience of the Rete Ematologica Pugliese (REP) over the past 17 years, aiming to define the impact of each patient's disease and transplant-related characteristics on outcomes. PATIENTS AND METHODS: We retrospectively studied 72 patients with HL who received allogeneic SCT from 2000 to 2017. At the time of allogeneic SCT, 33 (46%) patients had chemosensitive disease, and 39 (54%) were chemo-refractory. All patients received reduced-intensity conditioning, 50% received grafts from a matched sibling donor, and 50% from a matched-unrelated donor. RESULTS: With a median follow-up of 48 months (range, 3-195 months), 30 patients are alive, and 42 have died. The Kaplan-Meier estimates of overall survival and progression-free survival at 5 years were 35% and 34%, respectively. Following transplantation, 12 (17%) patients died of non-relapse mortality at a median of 90 days (range, 1 day-20 months). The causes of death included infection (n = 7), graft-versus-host disease (n = 3), and multi-organ failure (n = 2). CONCLUSIONS: Allogeneic SCT results extend survival in selected patients with relapsed/refractory HL, showing low treatment-related mortality. Patients with active disease at the time of allogeneic transplantation have poor outcomes. Allogeneic SCT may be an effective salvage strategy for patients who relapse after an autologous SCT.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/terapia , Acondicionamiento Pretrasplante/métodos , Adolescente , Adulto , Femenino , Enfermedad de Hodgkin/patología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
12.
Clin Lymphoma Myeloma ; 8(5): 294-9, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18854284

RESUMEN

BACKGROUND: Few studies have focused on factors affecting outcome in patients with multiple myeloma (MM) treated with thalidomide-based therapy. We investigated factors affecting response, progression-free survival (PFS), and overall survival (OS) in patients with MM treated with the thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) regimen with the aim to select patients benefiting more from this therapy. PATIENTS AND METHODS: Sixty-six patients with MM were treated first line with the ThaDD regimen. We analyzed demographics and disease-related characteristics to search for factors affecting response (> or = very good partial remission [VGPR] vs. < VGPR], PFS, and OS. RESULTS: Overall, 45 patients (68%) showed response > or = VGPR; median TTP and OS were 23.5 months and 35.5 months, respectively. Multivariate analysis selected only serum C-reactive protein (sCRP) as a predictive factor for response (P < .0001). By multivariate analysis, normal sCRP level (P = .001) and response to treatment > or = VGPR (P = .007) were found to be associated with longer PFS. The factors that remained significantly associated with a longer OS when assessed by multivariate analysis were normal sCRP level (P = .005) and response to therapy > or = VGPR (P = .019). CONCLUSION: Serum C-reactive protein before therapy and response after therapy are the only factors useful in identifying patients benefiting from anthracycline/thalidomide-based therapy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores/análisis , Proteína C-Reactiva/análisis , Mieloma Múltiple/sangre , Mieloma Múltiple/terapia , Anciano , Antraciclinas/administración & dosificación , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Análisis de Supervivencia , Talidomida/administración & dosificación , Resultado del Tratamiento
14.
Leuk Lymphoma ; 47(12): 2542-6, 2006 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-17169798

RESUMEN

Fifteen consecutive resistant/relapsed chronic lymphocytic leukemia (CLL) patients (median age: 65 years) received alemtuzumab for 16 consecutive weeks. All patients had negative CMV anti genemia at baseline. Five patients received oral acyclovir 800 mg twice a day for CMV prophylaxis and 10 patients got intravenous (iv) ganciclovir 7.5 mg/kg once a week. A total of five CMV reactivations occurred, four in the acyclovir and one in the ganciclovir prophylaxis group. Alemtuzumab was then discontinued and all patients were treated with iv ganciclovir 7.5 mg/kg per day. All patients achieved negative CMV anti genemia after a median of 15 days of therapy. Weekly iv ganciclovir prophylaxis and alemtuzumab treatment were then restarted without any further CMV reactivations. In conclusion, weekly iv ganciclovir appears feasible and effective in preventing CMV reactivation and disease in this setting of high-risk immunocompromised patients, allowing an easier management of a therapy otherwise difficult to be routinely used.


Asunto(s)
Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Antineoplásicos/administración & dosificación , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/administración & dosificación , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Anciano , Alemtuzumab , Anticuerpos Monoclonales Humanizados , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/complicaciones , Femenino , Humanos , Sistema Inmunológico/patología , Infusiones Intravenosas , Leucemia Linfocítica Crónica de Células B/complicaciones , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del Tratamiento
15.
Hematol J ; 4(1): 47-53, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12692520

RESUMEN

Elderly acute lymphoblastic leukemia (ALL) is a rare condition associated with low complete remission (CR) rate and short survival. In order to improve these results, we evaluate the efficacy and toxicity of Daunoxome, a liposomal daunorubicin, exhibiting toxicity profile and pharmacokinetic indices better than standard daunorubicin. In total, 15 consecutive patients with nonmature ALL were enrolled on a prospective phase II study. No exclusion was made because of older age, poor performance status and organ dysfunctions. Median age was 69 years; performance status resulted >/=2 in nine patients (60%), six patients (40%) were bcr-abl positive and two-thirds of the patients had comorbidities. Induction therapy consisted of vincristine, Daunoxome and dexamethasone. Patients in CR received one or two consolidation cycles of cyclophosphamide, cytarabine and topotecan followed, in patients achieving CR, by a two-year rotating maintenance course including vincristine, Daunoxome, cyclophosphamide and prednisone. In all, 11 patients (73%) achieved CR, three patients (20%) died early during the induction phase and one patient (7%) had resistant disease. Five patients (33%) relapsed after 5-21 months. With a median follow-up of 20 months, disease free survival (DFS) and overall survival (OS) at 2 years were 36 and 38%, respectively. Major toxicity included myelosuppression and infection. Our experience demonstrates that a high dose of daunorubicin as liposomal compound can be safely administered in elderly ALL, exhibiting high antitumor activity. Our therapeutic program shows evidence of benefit in DFS and OS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Linfoma de Burkitt/tratamiento farmacológico , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Betametasona/administración & dosificación , Enfermedades de la Médula Ósea/inducido químicamente , Linfoma de Burkitt/mortalidad , Comorbilidad , Ciclofosfamida/administración & dosificación , Citarabina/administración & dosificación , Daunorrubicina/administración & dosificación , Daunorrubicina/efectos adversos , Supervivencia sin Enfermedad , Portadores de Fármacos , Femenino , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Infecciones/etiología , Leucemia de Células T/tratamiento farmacológico , Leucemia de Células T/mortalidad , Tablas de Vida , Liposomas , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidad , Estudios Prospectivos , Inducción de Remisión , Seguridad , Análisis de Supervivencia , Topotecan/administración & dosificación , Resultado del Tratamiento
16.
Hematol J ; 5(4): 312-7, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15297847

RESUMEN

Thalidomide, the prototype of a new class of agents active against multiple myeloma (MM), exerts synergistic/additive effects when combined with other drugs. The aim of this study was to compare the toxicity and efficacy of thalidomide alone and in combination with oral melphalan. Patients with advanced MM received 100 mg/day oral thalidomide escalated weekly up to 600 mg/day (n=23; T group), alone or with 0.20 oral mg/kg/die melphalan administered monthly for four consecutive days (n=27; TM group). A>/=50% paraprotein reduction was observed in 59% of TM compared with 26% of T patients (P=0.009); three TM patients were found to have an absence of paraprotein by immunofixation. After a median follow-up of 13 months (range 6-32), progression-free survival (PFS) at 2 years was significantly longer in the TM group (61 versus 45%; P=0.0376), whereas overall survival did not differ significantly. Toxicity was not significantly greater with the combination therapy; although DVT was more frequent (11 versus 4%), as was grade 3 leukopenia (30 versus 13%; P=0.073), there were no cases of severe infection. Thalidomide administered with oral melphalan improved response rates and PFS in patients with advanced MM without significantly increasing severe toxicity.


Asunto(s)
Melfalán/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Talidomida/uso terapéutico , Administración Oral , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Melfalán/administración & dosificación , Melfalán/toxicidad , Persona de Mediana Edad , Mieloma Múltiple/mortalidad , Mieloma Múltiple/patología , Análisis de Supervivencia , Talidomida/administración & dosificación , Talidomida/toxicidad
18.
Leuk Lymphoma ; 52(5): 776-85, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21338282

RESUMEN

The literature provides scant data concerning infectious complications and their effect on the outcome of patients with multiple myeloma (MM) treated with new drug combinations. Despite no substantial myelotoxic effect, thalidomide increases the risk of severe infections in patients with MM. We studied 202 patients who received regimens containing thalidomide in order to assess the time, type, outcome, and factors affecting development of severe infections, role of antibiotic prophylaxis, and effect of severe infections on final outcome. Thirty-eight patients (19%) developed a severe infection early during induction therapy and most infections were pneumonia. Only one patient died due to septic shock during neutropenia. No significant differences were reported in terms of progression-free survival (PFS) and overall survival (OS) between patients developing a severe infection and those who did not. Multivariate analysis determined a monoclonal component >3 g/dL and platelets <130 ,000/µL as factors associated with increased risk of severe infection. Primary antibiotic prophylaxis significantly decreased the probability of severe infection only in patients having both the above risk factors. Patients with MM receiving thalidomide combinations with high tumor burden are at high risk of developing severe infections and require primary antibiotic prophylaxis, whereas in other patients it is questionable. However, patient final outcome was not affected by infection development.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Mieloma Múltiple/tratamiento farmacológico , Infecciones Oportunistas/inducido químicamente , Talidomida/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Mieloma Múltiple/complicaciones , Mieloma Múltiple/mortalidad , Infecciones Oportunistas/complicaciones , Infecciones Oportunistas/etiología , Infecciones Oportunistas/prevención & control , Probabilidad , Estudios Retrospectivos , Talidomida/efectos adversos , Trombosis de la Vena/etiología
19.
Leuk Lymphoma ; 51(8): 1444-9, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20496998

RESUMEN

The outcome of patients with multiple myeloma (MM) aged over 75 years remains poor, and the best therapeutic approach has still to be defined. We compared the response, toxicity, and outcome of 34 very elderly patients with MM receiving thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) to those of 34 patients matched for age, International Staging System (ISS), and creatinine who received melphalan, prednisone, thalidomide (MPT). ThaDD resulted in a significantly higher response: > or =PR (87.5% vs. 61.5%, p = 0.009) and > or =VGPR (55.5% vs. 29.5%; p = 0.03). No statistical differences were detected in terms of median probability of progression-free survival (PFS) and overall survival (OS) between the two treatments. Patients treated with MPT had more neutropenia, neuropathy, and heart toxicity, whereas thromboembolism resulted more frequently in patients receiving ThaDD. Therapy discontinuation occurred in 9% and 14.5% of patients treated with ThaDD and MPT, respectively. ThaDD can be considered a therapeutic option in very elderly patients with MM since it induces a faster and deeper response than that obtained with MPT, having similar safety profile.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Dexametasona/administración & dosificación , Doxorrubicina/administración & dosificación , Doxorrubicina/análogos & derivados , Humanos , Melfalán/administración & dosificación , Polietilenglicoles/administración & dosificación , Prednisona/administración & dosificación , Tasa de Supervivencia , Talidomida/administración & dosificación , Resultado del Tratamiento
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