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Background: Recurrence, even after years from the last treatment, characterizes lymphoproliferative disorders. Therefore, patients in complete remission from the disease should be followed up with periodic clinical checks. There is not a consensus on the role of imaging for this aim, because the radiological techniques used at the time of diagnosis expose patients to a risk of ionizing radiation damage. Whole-body magnetic resonance imaging with diffusion-weighted imaging (WB-MRI-DWI) has given similar results to gold standard techniques in detecting lymphoma in the involved sites without ionizing radiation. In this retrospective real-life study, we aimed to assess the accuracy of WB-MRI-DWI during follow-ups of lymphoma patients in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Methods: Lymphoma patients who were subject to at least one WB-MRI-DWI during follow-up between February 2010 and February 2022 were enrolled. Results: Based on our investigation, the calculated sensitivity of WB-MRI-DWI was 100% (95% CI: 99.4-100.0), the specificity was 98.6% (95% CI: 97.4-99.3), PPV was 79% (95% CI: 75.9-81.9), and NPV was 100% (95% CI: 99.4-100.0). Conclusions: Despite the possibility of poor patient compliance and the identification of false positives, WB-MRI-DWI examination demonstrated an excellent sensitivity in ruling out the disease relapse.
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Data on the efficacy of high-dose chemotherapy and autologous stem cell transplantation (ASCT) for classical Hodgkin lymphoma (cHL) patients who failed a PET-driven first-line therapy are limited.We retrospectively evaluated 220 adult cHL patients who underwent ASCT from 2009 to 2021 at 11 centers in Italy. Overall, 49.5% had refractory disease, 23.2% relapsed < 12 and 27.3% ≥12 months from the end of first-line chemotherapy. The 3-year progression-free survival (PFS) and overall survival (OS) were 73.8% and 89.4%. In univariable analysis for PFS events PET-2+ (HR 2.69, p = .001), anemia (HR 2.22, p = .019), refractory disease (HR 1.76, p = .045), less than CR before ASCT (HR 3.24, p < .001) and >2 lines of salvage therapy (HR 2.52; p = .004) were associated with a higher risk of failure after ASCT. In multivariable analysis, >2 lines of salvage therapy (HR 3.28, p = .004) and RT before ASCT (HR 3.00, p = 0.041) retained significance.ASCT is an effective salvage approach for cHL patients treated in the era of PET-adapted therapies.
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Trasplante de Células Madre Hematopoyéticas , Enfermedad de Hodgkin , Adulto , Humanos , Enfermedad de Hodgkin/terapia , Enfermedad de Hodgkin/tratamiento farmacológico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapia Recuperativa , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Retrospectivos , Trasplante Autólogo , Trasplante de Células Madre , Tomografía de Emisión de PositronesRESUMEN
The GIMEMA phase II LLC1518 VERITAS trial investigated the efficacy and safety of front-line, fixed-duration venetoclax and rituximab (VenR) in combination in young (≤65 years), fit patients with chronic lymphocytic leukemia and unmutated IGHV and/or TP53 disruption. Treatment consisted of the venetoclax ramp-up, six monthly courses of the VenR combination, followed by six monthly courses of venetoclax as a single agent. A centralized assessment of minimal residual disease (MRD) was performed by allele-specific oligonucleotide polymerase chain reaction assay on the peripheral blood and bone marrow at the end of treatment (EOT) and during the follow-up. The primary endpoint was the complete remission rate at the EOT. Seventy-five patients were enrolled; the median age was 54 years (range, 38-65), 96% had unmutated IGHV, 12% had TP53 disruption, and 4% had mutated IGHV with TP53 disruption. The overall response rate at the EOT was 94.7%, with a complete remission rate of 76%. MRD was undetectable in the peripheral blood of 69.3% of patients and in the bone marrow of 58.7% of patients. The 12-month MRD-free survival in the 52 patients with undetectable MRD in the peripheral blood at the EOT was 73.1%. After a median follow-up of 20.8 months, no cases of disease progression were observed. Three patients had died, two due to COVID-19 and one due to tumor lysis syndrome. The first report of the VERITAS study shows that front-line VenR was associated with a high rate of complete remissions and durable response with undetectable MRD in young patients with chronic lymphocytic leukemia and unfavorable genetic characteristics. ClinicalTrials.gov identifier: NCT03455517.
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COVID-19 , Leucemia Linfocítica Crónica de Células B , Humanos , Persona de Mediana Edad , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Leucemia Linfocítica Crónica de Células B/genética , Rituximab/efectos adversos , Neoplasia Residual/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversosRESUMEN
Although chemotherapy (CHT) exposure is an established cause of telomere attrition, determinants of telomere length (TL) dynamics after chemotherapy are poorly defined. In this study, we analyzed granulocyte telomere dynamics in 34 adult lymphoma patients undergoing first-line CHT. TL was measured by southern blot at each CHT cycle and after 1 year from CHT completion. Median age was 59 yrs (range 22-77). Median number of CHT cycles was 6 (range 3-6). The majority of patients (79%, n = 27) experienced TL shortening following CHT exposure. Mean telomere loss was 673 base pairs (bp) by cycle 6. Telomere shortening was an early event as 87% of the total telomere loss (mean 586 bp) occurred by the end of cycle 3, with no significant recovery after 1 year. A significant correlation was observed between baseline TL and total or fractional telomere loss (p < 0.001), with telomere shortening by cycle 3 observed predominantly in male patients with long telomeres at pre-treatment evaluation. Stratifying the analysis by gender and age only young women (<51 years of age) did not show significant telomere shortening following chemotherapy exposure. These findings indicate that gender and baseline TL are major determinants of TL dynamics following chemotherapy exposure in lymphoma patients.
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Linfoma , Adulto , Humanos , Masculino , Femenino , Adulto Joven , Persona de Mediana Edad , Anciano , Linfoma/tratamiento farmacológico , Linfoma/genética , Acortamiento del Telómero , TelómeroAsunto(s)
COVID-19/complicaciones , Leucemia Linfocítica Crónica de Células B/terapia , SARS-CoV-2/inmunología , Vacunación/métodos , Anciano , COVID-19/prevención & control , COVID-19/transmisión , COVID-19/virología , Manejo de la Enfermedad , Femenino , Humanos , Italia/epidemiología , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/virología , Masculino , Persona de Mediana Edad , Pronóstico , Factores de TiempoRESUMEN
Combined direct antineoplastic activity and the long-lasting immunological effects of allogeneic hematopoietic cell transplant (HCT) can cure many hematological malignancies, but broad adoption requires non-relapse mortality (NRM) rates and graft-versus-host disease (GVHD) control. Recently, posttransplant cyclophosphamide (PTCy) given after a bone marrow transplant significantly reduced GVHD-incidence, while PTCy given with tacrolimus/mofetil mycophenolate (T/MMF) showed activity following allogeneic peripheral blood stem cell transplantation (alloPBSCT). Here, we report the experience of a larger cohort (85 consecutive patients) and expanded follow-up period (03/2011-12/2019) with high-risk hematological malignancies who received alloPBSCT from Human-Leukocyte-Antigens HLA-matched unrelated/related donors. GVHD-prophylaxis was PTCy 50 mg/kg (days+3 and +4) combined with T/MMF (day+5 forward). All patients stopped MMF on day+28 with day+110 = median tacrolimus discontinuation. Cumulative incidences were 12% for acute and 7% for chronic GVHD- and no GVHD-attributed deaths. For surviving patients, the 12, 24, and 36-month probabilities of being off immunosuppression were 92, 96, and 96%, respectively. After a 36-month median follow-up, NRM was 4%; median event-free survival (EFS) and overall survival (OS) had yet to occur. One- and two-year chronic GVHD-EFS results were 57% (95% CI, 46-68%) and 53% (95% CI, 45-61%), respectively, with limited late infections and long-term organ toxicities. Disease relapse caused the most treatment failures (38% at 2 years), but low transplant toxicity allowed many patients (14/37, 38%) to receive donor lymphocyte infusions as a post-relapse strategy. We confirmed that PTCy+T/MMF treatment effectively prevented acute and chronic GVHD and limited NRM to unprecedented low rates without loss of disease control efficacy in an expanded patient cohort. This trial is registered at U.S. National Library of Medicine as #NCT02300571.
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Host immune homeostasis as an independent prognostic indicator has been inadequately evaluated in aggressive non-Hodgkin's lymphomas (NHL). The present study addresses the prognostic significance in aggressive NHLs of the immunologic profile evaluated by pretreatment serum levels of immunoglobulins (Ig) and lymphocyte-monocyte ratio (LMR). In this series of 90 patients with aggressive lymphoma, the median level for IgG was 1,024mg/dl (range 436-2236), and for LMR was 2.2 (range 0.2-13.8). CR rate was higher with IgG levels ≥1,024mg/dL (91% vs 77% p=0.059). LMR ≤ 2.2 was associated with lower 1-year PFS (73% vs. 92%, p 0.016). Patients with good/very good R-IPI showed a reduced PFS if IgG or LMR was low, while patients with poor R-IPI did better if LMR or IgG levels were high. We combined both parameters with the R-IPI and produced a four-risk prognostic score showing one-year PFS of 95% (95% CI 68%-99%), 100% (95% CI 100%-100%), 73% (95% CI 52%-86%), and 59% (95% CI 31%-79%), in patients with zero, one, two and three risk factors, respectively. The results indicate for the first time the value of baseline serum Ig levels in the prognostic assessment of aggressive lymphoma.
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The GIMEMA group investigated the efficacy, safety, and rates of discontinuations of the ibrutinib and rituximab regimen in previously untreated and unfit patients with chronic lymphocytic leukemia (CLL). Treatment consisted of ibrutinib, 420 mg daily, and until disease progression, and rituximab (375 mg/sqm, given weekly on week 1-4 of month 1 and day 1 of months 2-6). This study included 146 patients with a median age of 73 years, with IGHV unmutated in 56.9% and TP53 disrupted in 22.2%. The OR, CR, and 48-month PFS rates were 87%, 22.6%, and 77%, respectively. Responses with undetectable MRD were observed in 6.2% of all patients and 27% of CR patients. TP53 disruption (HR 2.47; p = 0.03) and B-symptoms (HR 2.91; p = 0.02) showed a significant and independent impact on PFS. The 48-month cumulative rates of treatment discontinuations due to disease progression (DP) or adverse events (AEs) were 5.6% and 29.1%, respectively. AEs leading more frequently to treatment discontinuation were atrial fibrillation in 8% of patients, infections in 8%, and non-skin cancers in 6%. Discontinuation rates due to AEs were higher in male patients (HR: 0.46; p = 0.05), patients aged ≥70 years (HR 5.43, p = 0.0017), and were managed at centers that enrolled <5 patients (HR 5.1, p = 0.04). Patients who discontinued ibrutinib due to an AE showed a 24-month next treatment-free survival rate of 63%. In conclusion, ibrutinib and rituximab combination was an effective front-line treatment with sustained disease control in more than half of unfit patients with CLL. Careful monitoring is recommended to prevent and manage AEs in this patient population.
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Among patients with advanced-stage classical Hodgkin lymphoma (cHL) receiving ABVD chemotherapy, PET performed after the first two treatment cycles (PET-2) has prognostic value. However, 15% of patients with a negative PET-2 will experience treatment failure. Here we prospectively evaluated serum thymus and activation-regulated chemokine (TARC) levels, to improve risk assessment in patients treated according to HD0607 PET-driven trial (#NCT00795613). In 266 patients with available serum samples, who have agreed to participate in a sub-study for assessment of the role of TARC monitoring, serum TARC levels were measured at baseline and at time of PET-2 by commercially available ELISA test kits. The primary end-point was to evaluate the association between TARC after 2 ABVD cycles and PFS. Median TARC-2 values were significantly higher in PET-2-positive patients compared to PET-2-negative patients (P = .001), and in patients with treatment failure compared to those in continuous CR (P = .01). The 4-year PFS significantly differed between patients with TARC-2 >800 pg/mL vs ≤800 pg/mL (64% vs 86%, P = .0001). Moreover, among PET-2-negative patients, elevated TARC-2 identified those with a worse prognosis (74% vs 89%; P = .01). In multivariable analysis, TARC-2 >800 pg/mL was a significant independent predictor of PFS in the whole study population (HR 2.39, P = .004) and among the PET-2-negative patients (HR 2.49, P = .02). In conclusion, our results indicate that TARC-2 serum levels above 800 pg/mL suggest the need for a stringent follow-up in PET-2-negative patients, and the evaluation of new drugs in PET-2-positive, who will likely fail to respond to intensification with escalated BEACOPP.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/sangre , Quimiocina CCL17/sangre , Enfermedad de Hodgkin/patología , Tomografía de Emisión de Positrones/métodos , Adolescente , Adulto , Femenino , Estudios de Seguimiento , Enfermedad de Hodgkin/sangre , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Tasa de Supervivencia , Adulto JovenRESUMEN
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-ß, 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-ß 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.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Becaplermina/sangre , Factor 2 de Crecimiento de Fibroblastos/sangre , Factor de Crecimiento de Hepatocito/sangre , Mieloma Múltiple/sangre , Mieloma Múltiple/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/sangre , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Médula Ósea , Femenino , Estudios de Seguimiento , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Curva ROCRESUMEN
Many patients with B-cell malignancies can be successfully treated, although tumor eradication is rarely achieved. T-cell-directed killing of tumor cells using engineered T-cells or bispecific antibodies is a promising approach for the treatment of hematologic malignancies. We investigated the efficacy of CD19xCD3 DART bispecific antibody in a broad panel of human primary B-cell malignancies. The CD19xCD3 DART identified 2 distinct subsets of patients, in which the neoplastic lymphocytes were eliminated with rapid or slow kinetics. Delayed responses were always overcome by a prolonged or repeated DART exposure. Both CD4 and CD8 effector cytotoxic cells were generated, and DART-mediated killing of CD4+ cells into cytotoxic effectors required the presence of CD8+ cells. Serial exposures to DART led to the exponential expansion of CD4 + and CD8 + cells and to the sequential ablation of neoplastic cells in absence of a PD-L1-mediated exhaustion. Lastly, patient-derived neoplastic B-cells (B-Acute Lymphoblast Leukemia and Diffuse Large B Cell Lymphoma) could be proficiently eradicated in a xenograft mouse model by DART-armed cytokine induced killer (CIK) cells. Collectively, patient tailored DART exposures can result in the effective elimination of CD19 positive leukemia and B-cell lymphoma and the association of bispecific antibodies with unmatched CIK cells represents an effective modality for the treatment of CD19 positive leukemia/lymphoma.
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Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD-negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Enfermedad de Hodgkin/tratamiento farmacológico , Adolescente , Adulto , Bleomicina/administración & dosificación , Ciclofosfamida/administración & dosificación , Dacarbazina/administración & dosificación , Doxorrubicina/administración & dosificación , Etopósido/administración & dosificación , Estudios de Factibilidad , Femenino , Enfermedad de Hodgkin/diagnóstico por imagen , Enfermedad de Hodgkin/mortalidad , Enfermedad de Hodgkin/patología , Humanos , Ganglios Linfáticos/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Prednisona/administración & dosificación , Procarbazina/administración & dosificación , Estudios Prospectivos , Radioterapia , Rituximab/administración & dosificación , Análisis de Supervivencia , Vinblastina/administración & dosificación , Vincristina/administración & dosificación , Adulto JovenRESUMEN
AIM: Our study aimed to investigate the role of qualitative and quantitative whole body MRI with DWI for assessment of bone marrow involvement (BMI) in newly diagnosed lymphoma using FDG PET-CT and bone marrow biopsy (BMB) as reference standard. MATERIALS AND METHODS: We retrospectively evaluated 56 patients with newly diagnosed lymphoma (21 Hodgkin's lymphoma and 35 non-Hodgkin's lymphoma) who underwent random unilateral BMB, FDG PET-CT and Wb-MRI-DWI for initial staging. In a patient-based analysis, results of Wb-MRI-DWI were compared with FDG PET-CT and BMB. For quantitative analysis, mean ADC values of posterior iliac crest were correlated with BMI and bone marrow cellularity. RESULTS: WB-MR-DWI obtained excellent concordance with FDG PET-CT both in HL (k = 1.000; 95% CI 1.000-1.000) and in DLBCL (k = 1.000; 95% CI 1.000-1.000). In other NHL, WB-MRI-DWI obtained a good correlation with BMB (k = 0.611; 95% CI 0.295-0.927) while FDG PET-CT had poor concordance (k = 0.067; 95% CI 0.372-0.505). WB-MR-DWI has no false negative errors but 4 false positive results consisting in focal lesions consensually reported by FDG PET-CT and resolved after therapy. No significant correlation between ADC mean value and BMI was found (p = 0.0586). CONCLUSION: Our data suggest that Wb-MRI-DWI is a valid technique for BMI assessment in lymphoma patients, thanks to its excellent concordance with FDG PET-CT and good concordance with BMB (superior than FDG PET-CT). If further investigations will confirm our results on larger patient groups, it could become a useful tool in the clinical workup.
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Médula Ósea/diagnóstico por imagen , Médula Ósea/patología , Imagen de Difusión por Resonancia Magnética/métodos , Linfoma/diagnóstico por imagen , Linfoma/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Imagen de Cuerpo Entero , Adolescente , Adulto , Anciano , Biopsia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
INTRODUCTION: We investigated for a possible role for peritransplantation involved-field radiotherapy (IFRT) by comparing patients who received IFRT before after autologous stem cell transplantation (ASCT) and patients who received salvage chemotherapy (CT) alone. PATIENTS AND METHODS: We retrospectively evaluated 73 consecutive patients with Hodgkin lymphoma treated with ASCT between 2003 and 2014. Twenty-one patients (28.8%) received peritransplantation radiotherapy. A Cox regression analysis (multivariate analysis; MVA) was performed to evaluate the prognostic role of any risk factor. Overall survival (OS) and progression-free survival (PFS) were calculated from the date of ASCT. Response to CT and ASCT were evaluated with positron emission tomography (PET) scan. RESULTS: Median follow-up was 41 months (range, 1-136 months). Overall, no significant difference appeared between patients who received IFRT and patients treated with CT alone; however, patients who were treated with IFRT had worse prognostic factors. In the MVA, advanced stage at relapse and persistent disease before ASCT (evident on PET scan [PET+]) were related to worse PFS and OS. In patients with limited stage disease at relapse and PET+, peritransplantation radiotherapy showed higher 3-year OS rates (91.7% vs. 62.3%) and PFS rates (67.5% vs. 50%) compared with patients treated with CT alone, although this difference was not significant (P = .14 and P = .22, respectively). CONCLUSION: IFRT used before or after ASCT might partially compensate for worse prognostic factors among the overall population; subgroup analysis showed a trend for survival benefit at 3 years in patients with limited stage disease at relapse and PET+ before ASCT.
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Enfermedad de Hodgkin/radioterapia , Enfermedad de Hodgkin/cirugía , Linfoma/radioterapia , Linfoma/cirugía , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Estudios de Seguimiento , Trasplante de Células Madre Hematopoyéticas/métodos , Enfermedad de Hodgkin/tratamiento farmacológico , Humanos , Linfoma/tratamiento farmacológico , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Tomografía de Emisión de Positrones/métodos , Recurrencia , Estudios Retrospectivos , Terapia Recuperativa/métodos , Trasplante Autólogo/métodosRESUMEN
BACKGROUND: Primary refractory disease is a main challenge in the management of non-Hodgkin's Lymphoma (NHL). This survey was performed to define the rate of refractory disease to first-line therapy in B and T-cell NHL subtypes and the long-term survival of primary refractory compared to primary responsive patients. METHODS: Medical records were reviewed of 3,106 patients who had undergone primary treatment for NHL between 1982 and 2012, at the Hematology Centers of Torino and Bergamo, Italy. Primary treatment included CHOP or CHOP-like regimens (63.2%), intensive therapy with autograft (16.9%), or other therapies (19.9%). Among B-cell NHL, 1,356 (47.8%) received first-line chemotherapy with rituximab. Refractory disease was defined as stable/progressive disease, or transient response with disease progression within six months. RESULTS: Overall, 690 (22.2%) patients showed primary refractory disease, with a higher incidence amongst T-cell compared to B-cell NHL (41.9% vs. 20.5%, respectively, p<0.001). Several other clinico-pathological factors at presentation were variably associated with refractory disease, including histological aggressive disease, unfavorable clinical presentation, Bone Marrow involvement, low lymphocyte/monocyte ration and male gender. Amongst B-cell NHL, the addition of rituximab was associated with a marked reduction of refractory disease (13.6% vs. 26.7% for non-supplemented chemotherapy, p<0.001). Overall, primary responsive patients had a median survival of 19.8 years, compared to 1.3 yr. for refractory patients. A prolonged survival was consistently observed in all primary responsive patients regardless of the histology. The long life expectancy of primary responsive patients was documented in both series managed before and after 2.000. Response to first line therapy resulted by far the most predictive factor for long-term outcome (HR for primary refractory disease: 16.52, p<0.001). CONCLUSION: Chemosensitivity to primary treatment is crucial for the long-term survival in NHL. This supports the necessity of studies aimed to early identify refractory disease and to develop different treatment strategies for responsive and refractory patients.
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Resistencia a Antineoplásicos , Linfoma de Células B/tratamiento farmacológico , Linfoma de Células T/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
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.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Ácidos Borónicos/administración & dosificación , Ácidos Borónicos/efectos adversos , Bortezomib , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Inducción , Estimación de Kaplan-Meier , Quimioterapia de Mantención , Masculino , Melfalán/administración & dosificación , Melfalán/efectos adversos , Persona de Mediana Edad , Neutropenia/inducido químicamente , Enfermedades del Sistema Nervioso Periférico/inducido químicamente , Prednisona/administración & dosificación , Prednisona/efectos adversos , Pirazinas/administración & dosificación , Pirazinas/efectos adversos , Talidomida/administración & dosificación , Talidomida/efectos adversos , Trombocitopenia/inducido químicamente , Resultado del TratamientoRESUMEN
Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six elderly (>65 years) newly diagnosed MM patients from six European randomized trials were retrospectively analyzed and matched for age, albumin, and beta2-microglobulin at diagnosis, 296 patients were selected from the VMP groups, and 294 from MPT. Complete response rate was 21% in the VMP patients and 13% in the MPT patients (P = 0.007). After a median follow-up of 34 months (range, 1-92), VMP significantly prolonged both PFS (median 32.5 vs. 22.9 months, HR 0.65; 95% CI 0.52-0.82; P < 0.001) and OS (median 79.7 vs. 45.1 months, HR 0.44; 95% CI 0.32-0.59; P < 0.001) in comparison with MPT. The benefit in terms of OS of the VMP group was quite similar among patients with different risk factors defined by sex, ISS, ECOG performance status, or serum creatinine but not among patients ≥ 75 years. Multivariate analysis confirmed that VMP was an independent predictor of longer PFS and OS. In a control-case matched analysis, PFS and OS were prolonged in patients who received VMP in comparison with those treated with MPT.