15 research outputs found
Validation of a new prognostic index in patients with early chronic lymphocytic leukemia : the GIMEMA experience
No full textA gender-based score system predicts the clinical outcome of patients with early B-cell chronic lymphocytic leukemia
No full textTo facilitate the development of a prognostic model for early B-cell chronic lymphocytic leukemia (CLL), the Gruppo Italiano Malattie EMatologiche Maligne dell'Adulto (GIMEMA) proposes its multi-institutional effort as a working model. In total, 1138 newly diagnosed Binet stage A patients managed over the last 10 years outside the setting of clinical trials according to a "wait and see" policy form the basis of the present study aimed at investigating prognostic variables affecting disease progression, a surrogate endpoint for overall survival. A 3-stage risk system, simply obtained by summing the variables that proved significant in the multivariate analysis (i.e. short lymphocyte doubling time, advanced Rai substage, high peripheral blood lymphocytosis), is proposed. Clear-cut differences in the 10 year progression-free survival (PFS) were observed among patients scoring 0 (low risk), 1 (intermediate risk), 2 - 3 (high risk): 67.8, 41.0 and 24.8%, respectively (P < 0.0001). The results of the Medical Research Council (MRC) suggesting a better clinical outcome for females prompted us to verify such a gender-related difference within our prognostic categories. Because changes in PFS only reflected gender for patients scoring 0 (P = 0.04), the following prognostic subgroups are proposed: (1) females scoring 0; (2) males scoring 0; (3) patients scoring 1 - 3 whatever gender (10 year PFS: 76.2, 61.4 and 37.8%; P < 0.00001). Our long-term database provides an adequate patient sample to generate a generalized risk stratification model based on clinical data. The indolent clinical outcome of women with early CLL is also supported by the higher frequency of the immunoglobulin heavy-chain variable (IgVH) mutational status and lower proportion of 17p and 11q deletions found in such a patient subset in the MRC CLL4 trial. © 2005 Taylor & Francis Group Ltd
Relationship between autoimmune phenomena and disease stage and therapy in B-cell chronic lymphocytic leukemia
No full textThe aim of this multicenter GIMEMA study was to correlate autoimmune complications (AIC) in B-cell chronic lymphocytic leukemia (B-CLL) with stage and therapy. Autoimmune hemolytic anemia (129/194 cases) and autoimmune thrombocytopenia (35/194 cases) were typically present in advanced and multi-treated disease. Age over the median, stage C and first and second line therapy were identified as independent risk factors by multivariate analysis. In contrast, non-hematologic AIC (30/194 cases) and the presence of serological markers of autoimmunity were mostly observed in early B-CLL, suggesting different pathogenic mechanisms underlying hematologic and non-hematologic autoimmune phenomena in B-CLL
HBV REACTIVATION IN CLL PATIENTS WITH OCCULT HBV INFECTION TREATED WITH IBRUTINIB WITH OR WITHOUT VIRAL PROPHYLAXIS. A RETROSPECTIVE MULTICENTRIC GIMEMA STUDY
No full textBackground: Chemo-immunotherapy (CIT) is associated to an in-
creased risk of HBV reactivation in patients (pts) affected by lympho-
proliferative disorders. Occult hepatitis B infection (OBI) is defined by
the presence of anti-HBc antibodies, HBsAg negativity with or without
anti-HBs antibodies and HBV-DNA serum negativity. Guidelines suggest
lamivudine prophylaxis in OBI/CLL pts treated with CIT. No data are
available about the need for prophylaxis in OBI/CLL pts treated with
BTK inhibitors.
Aims: The objective of this study is to evaluate if OBI/CLL pts need
lamivudine or HBV-DNA monitoring. Methods:We analyzed 111 OBI/CLL pts (14%), among 781 CLL pts
treated with IBR in 22 Italian GIMEMA centres until January 2019. Me-
dian age was 64 years. At IBR start, 9%, 48%, 42% pts were on Binet
stage A, B, C respectively; 71% pts had unmutated IGHV, 26% pts had 17p deletion. Twenty-six (23%) OBI/CLL pts were treatment naïve at
IBR start; 44 (40%) pts, 18 (16%) and 23 (20%) had been previously
treated with 1, 2 or >2 lines of CIT respectively. Seventy-three OBI/CLL
pts on IBR underwent prophylaxis with lamivudine, while 38 pts were
only subjected to HBV-DNA monitoring every 3 months. Table1.
Results:Viral reactivation was observed in 5 pts. Four of them (2 with
clinical reactivation and 2 with serological one) belonged to the HBV-
DNA monitoring group; one patient experienced clinical reactivation on
the lamivudine prophylaxis group (p=0.046). Both kinds of reactivation
occurred in the first 3-6 months of IBR. In the HBV-DNA monitoring
group, one patient was treatment naïve and experienced only serological
reactivation; 3 pts were previously treated with CIT, at least 12 months
before the IBR, and experienced both serological (1) and clinical (2) ac-
tivation Table1. Serological reactivation was only recorded on the HBV-
DNA monitoring group as those were the only pts who underwent a
systematic screening schedule in the following months, thus were diag-
nosed with HBV reactivation (and treated with lamivudine) in the ab-
sence of any clinical suspicion.
Conclusions:From the collected evidence, it seems reasonable to sug-
gest that prophylactic treatment should be considered appropriate and
started in pts who were previously treated with CIT. For the treatment
naïve group, a clinical choice could be performed, knowing that reacti-
vation could seldomly occur and be detected in time to promptly treat
the pts, but prophylaxis is not mandatory for a favourable clinical course
An Italian retrospective study on the routine clinical use of low-dose alemtuzumab in relapsed/refractory chronic lymphocytic leukaemia patients
No full textLow-dose alemtuzumab has shown a favourable toxicity profile coupled with good results in terms of efficacy in relapsed/refractory chronic lymphocytic leukaemia (CLL). We conducted a multicentre retrospective study on the routine clinical use of low-dose alemtuzumab in this patient setting. One hundred and eight relapsed/refractory CLL patients from 11 Italian centres were included in the analysis. All patients had an Eastern Cooperative Oncology Group performance status ≤2 and the majority (84%) had adenopathies <5cm. Low-dose alemtuzumab was defined as a total weekly dose ≤45mg and a cumulative dose ≤600mg given for up to 18weeks. The overall response rate was 56% (22% complete remissions). After a median follow-up of 42·2months, the median overall survival and progression-free survival were 39·0 and 19·4months, respectively. In univariate analysis, response was inversely associated with lymph node (P=0·01) and spleen (P=0·02) size, fludarabine-refractoriness (P=0·01) and del(11q) (P=0·009). Advanced age and del(17p) were not associated with a worse outcome. Cumulative dose of alemtuzumab was not associated to response. Toxicities were usually mild and manageable; severe infections occurred in seven patients (7%) during therapy. This retrospective analysis confirms that low-dose alemtuzumab is a valid and currently used therapeutic option for the treatment of relapsed/refractory CLL. © 2011 Blackwell Publishing Ltd
Efficacy of front-line ibrutinib and rituximab combination and the impact of treatment discontinuation in unfit patients with chronic lymphocytic leukemia : results of the Gimema LLC1114 Study
No full text: 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
PROGNOSIS IN CHRONIC LYMPHOCYTIC-LEUKEMIA - A RETROSPECTIVE MULTICENTRIC STUDY FROM THE GIMEMA GROUP
No full textClinical and biological data were evaluated using Desu univariate analyses or Cox multivariate analyses in a series of 1,777 chronic lymphocytic leukemia (CLL) patients from an Italian Cooperative Group. In univariate analyses, age and sex of patients, presence of bone marrow (BM; greater than or equal to 50%), and peripheral blood (PB; greater than or equal to 60,000/microL) lymphocytosis, anemia (hemoglobin [Hb] less than 11 g/dL), thrombocytopenia (less than 100,000/microL), direct Coombs' test positivity, hepatomegaly, splenomegaly, and extent of lymph node involvement were shown to be of significant prognostic value. Multivariate analyses, through a stepwise procedure, showed that the most important prognostic variables are Hb, hepatomegaly, lymph node involvement, PB lymphocytosis, and age and sex of patients. Further covariates would produce an improvement having a nonsignificant P value. Based on the results of multivariate analyses, a four-step staging using the significant variables of the Cox model is proposed
Efficacy of Front-Line Ibrutinib and Rituximab Combination and the Impact of Treatment Discontinuation in Unfit Patients with Chronic Lymphocytic Leukemia: Results of the Gimema LLC1114 Study
No full textThe 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
DP043 | AN MRD-GUIDED FRONTLINE TREATMENT FOR YOUNG PATIENTS WITH HIGH-RISK CLL INCLUDING VENETOCLAX AND OBINUTUZUMAB FOLLOWED BY VENETOCLAX AND ZANUBRUTINIB IN PATIENTS WITH DETECTABLE MINIMAL RESIDUAL DISEASE: PRELIMINARY RESULTS FROM GIMEMA CLL2222 – VIS TRIAL
No full textA significant proportion of patients with chronic lymphocytic leukemia (CLL) who undergo a fixed-duration treatment with the venetoclax and obinutuzumab (VenO) combination achieved undetectable minimal residual disease (uMRD) with more prolonged progression-free survival than those with detectable MRD (dMRD). Therefore, a treatment strategy aimed at reducing residual disease may enhance outcomes for this latter group of patients. The GIMEMA CLL2222 (VIS) study is a multicenter, phase 2 trial investigating a front-line MRD-guided treatment approach for young (≤65 years) patients with high-risk CLL, defined by the presence of unmutated IGHV and/or TP53 disruption (TP53 mutation and/or deletion). Here, we provide preliminary data from this study. The study design includes an initial phase with six VenO courses. At the end of the VenO combination therapy (EOCT, month 9), MRD is evaluated by ASO-PCR, both in the peripheral blood (PB) and bone marrow (BM). Patients with uMRD (<10-4) continue treatment with 6 additional courses of venetoclax. Those patients with dMRD receive the venetoclax and zanubrutinib combination (VenZan) until cycle 21. This study has two co-primary endpoints: 1. the rate of patients who achieved uMRD at the EOCT with VenO. 2. the rate of patients with dMRD at the EOCT who reach uMRD at the EOT with the VenZan combination. The planned enrollment for this study is 78 patients. As of March 2025, 49 patients started treatment. The median age was 59 years, 98% of patients were IGHV unmutated, and one IGHV mutated withTP53 disruption. Currently, the study's primary endpoint has been met, with 22 out of 26 (85%) evaluated patients showing uMRD in both PB and BM at the EOCT. The remaining 4 patients with dMRD at the EOCT started the VenZan combination. Adverse events were those usually described in patients receiving study drugs. Obinutuzumab was discontinued in one patient due to a severe infusion reaction. No disease progression or deaths have been reported. The preliminary data from this study show a high rate of deep responses with uMRD in patients carrying high-risk genetic features who received VenO. In the next phase of this study, the threshold for uMRD will be lowered to <10-6, extending treatment with VenZan to patients with residual leukemic cells between <10-4 and ≤10-6 to reduce further residual disease improving outcomes for patients with high-risk genetics, who tend to lose response rapidly
The utility of a prognostic index for predicting time to first treatment (TFT) in early chronic lymphocytic leukemia (CLL): the GIMEMA (Gruppo Italiano Malattie Ematologiche dell' Adulto) experience
No full textBACKGROUND: A prognostic index based on widely available clinical and laboratory features was recently proposed to predict survival in patients with previously untreated chronic lymphocytic leukemia. We assessed the utility of this index for predicting time to first treatment in early chronic lymphocytic leukemia. DESIGN AND METHODS: An observational database of the GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto), which included 310 patients with newly diagnosed Binet stage A chronic lymphocytic leukemia who were observed at different primary hematology centers during the period 1991 - 2000, was used for the purpose of this study. RESULTS: The new prognostic index enabled Binet stage A patients to be divided into two subgroups that differed with respect to time to first treatment (P=0.003). The original prognostic index was derived from a database that included cases observed at a reference academic center; these patients were younger (P<0.0001) and had more advanced disease (P<0.0001) than those in the current investigation, which studied community-based patients whose data were recorded at presentation. With this in mind, we used an optimal cut-off search to determine how best to split patients with Binet stage A disease into different prognostic groups. According to the recursive partitioning (RPART) model, a classification tree was built that identified three subsets of patients who scores were 0-2 (low risk), 3-4 (intermediate risk) and 5-7 (high risk). The probability of remaining free from therapy at 5 years was 100% in the low risk group, 81.2% in the intermediate risk group and 61.3% in the high risk group (P<0.0001). CONCLUSIONS: The results of this study confirm the utility of a new prognostic index for predicting time to first treatment in a large sample series of community-based patients with early stage chronic lymphocytic leukemia at presentation. Our effort to develop a revised scoring method meets the need to separate Binet stage A patients into different prognostic groups in order to devise individualized and tailored follow-up during the treatment-free period
