scholarly journals Choosing the Right Treatment Option for the Right R/M HNSCC Patient: Should We Adhere to PFE for First-Line Therapy?

2021 ◽  
Vol 11 ◽  
Author(s):  
Katharina Lübbers ◽  
Mykola Pavlychenko ◽  
Theresa Wald ◽  
Susanne Wiegand ◽  
Andreas Dietz ◽  
...  
Keyword(s):  
Cox Regression ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Real World Evidence ◽  
Consumption Benefit ◽  
Outcome Differences ◽  
The Right ◽  
High Level

BackgroundThe landmark EXTREME trial established cisplatin, 5-fluorouracil and cetuximab (PFE) as first-line chemotherapy (1L-ChT) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We were interested in outcome differences of R/M HNSCC in 1L-ChT and factors influencing outcome in certain subgroups, especially patients receiving PFE, and the value of PFE compared to other 1L-ChT regimens to provide real world evidence (RWE).MethodsFor this retrospective monocentric study, 124 R/M HNSCC patients without curative surgical or radiotherapy options receiving at least one cycle of 1L-ChT were eligible. We analyzed their outcome using Kaplan-Meier plot and Cox regression to identify predictors for prolonged survival.ResultsSubgroups benefiting significantly from PFE were patients suffering from an index HNSCC outside the oropharynx. The PFE regimen proved to be superior to all other 1L-ChT regimens in clinical routine. Significant outcome differences between PFE treatment within or outside controlled trials were not seen.ConclusionThis retrospective analysis provides RWE for factors linked to improved outcome. Subgroup analyses highlight the lasting value of PFE among the growing spectrum of 1L-ChT. Importantly, fit smokers with high level alcohol consumption benefit from PFE; considering the patient’s lifestyle factors, PFE should not be ignored in decision-making.

191 Association of immune related adverse events with the efficacy of immune checkpoint inhibitors in metastatic renal cell carcinoma

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A205-A206
Author(s):  
Vasilii Bushunow ◽  
Leonard Appleman ◽  
Roby Thomas
Keyword(s):  
Renal Cell Carcinoma ◽  
Adverse Events ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier

BackgroundImmune checkpoint inhibitors (ICI) are first-line therapy for tumors including metastatic renal cell carcinoma (mRCC). Use of ICI is complicated by diverse immune-related adverse events (irAEs), which can add significant morbidity but are also associated with improved efficacy of therapy.1 2 Risk factors for development of irAE are still poorly understood. We hypothesized that patients with mRCC treated with ICI as first-line therapy have higher rates of developing irAE’s than patients previously treated with other therapies.MethodsWe conducted a single-institution, retrospective medical record review of patients with mRCC treated with immune-checkpoint inhibitors from March 2011 through April 15, 2020. We identified therapy duration, and presence, severity, and treatment of adverse events. We defined overall survival as time elapsed from date of diagnosis until death or until completion of study. We classified severity of adverse events according to CTCAE guidelines. Statistical methods included univariate Cox proportional hazards and logistic regression models, and Kaplan-Meier curves were plotted for subgroups.ResultsA total of 64 unique charts were reviewed. 18 patients (28%) of patients were treated with ICI as first-line therapy. 28 patients (44%) experienced immune-related adverse events with a total of 40 irAE’s identified. Most irAE were grade I-II (78%), with 7 (17%) grade III and 1 (2.4%) grade IV irAE’s. Most common sites were skin (29%), thyroid (20%) and gastrointestinal (15%). Patients with irAE had increased survival compared to those who did not have irAE (median survival not reached, vs 139 weeks, p=0.0004) (figure 1). This finding remained after excluding patients who had only experienced dermatologic irAE (median survival not reached in non-derm irAE subgroup, vs 144 weeks for dermatologic or no irAE, p=0.01) (figure 2). Patients treated with ICI as first line therapy had greater rates of developing irAE (72%) than those who had prior therapies (32%) (OR 5.4; p = 0.006). There was no association between histology type and rate of irAE.Abstract 191 Figure 1Kaplan-Meier survival plot of OS between patients with any irAE and those without any irAEAbstract 191 Figure 2Kaplan-Meier survival plot of OS between patients with non-dermatologic irAE and those without any irAE or only dermatologic irAEConclusionsThe development of irAE’s in patients with mRCC treated with ICI is associated with longer survival. This study joins the growing body of evidence showing that presence of irAE’s is associated with increased treatment efficacy. Use of ICI as first-line therapy is associated with higher risk of irAE. Given growing use of ICI as first-line therapy, further study to predict onset and severity of irAE’s is required.AcknowledgementsHong Wang, PhD, for statistical support.Ethics ApprovalThis study was approved by the University of Pittsburgh Institutional Review Board. Approval number STUDY19100386.ReferencesElias R, Yan N, Singla N, Levonyack N, Formella J, Christie A, et al. Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients. J Clin Oncol 2019;37(7):S645.Verzoni E, Cartenì G, Cortesi E, et al. Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. J Immunother Cancer 2019;7(1):99.

Anaphylactic shock: are we doing enough and with the right timing and order?

2015 ◽  
Vol 53 (3) ◽  
pp. 191-198
Author(s):  
H. Bălan ◽  
Adriana Gurghean
Keyword(s):  
Anaphylactic Shock ◽  
Good Practice ◽  
Fluid Replacement ◽  
First Line ◽  
Good Opportunity ◽  
First Line Therapy ◽  
Line Therapy ◽  
Practice Parameters ◽  
Golden Standard ◽  
The Right

Abstract Anaphylactic shock became, unfortunately, a common presence in Romanian mass-media, due to some fatal cases in the last months. The coincidence that in December 2014 the American Academy of Allergy, Asthma and Immunology, the American College of Allergy, Asthma and Immunology, and the Joint Council of Allergy Asthma and Immunology released Practice parameters offers a good opportunity to renew for all practitioners what is now considered the “golden standard” of good practice. Epinephrine must be considered the cornerstone and the most urgent measure to be applied in these cases, immediately after the diagnosis. A very important notice is to forget the administration of antihistamines or corticosteroids as first line therapy instead of epinephrine. Proper positioning of the subjects and quick fluid replacement (1-2 l of normal saline in a few minutes) are also mandatory.

scholarly journals Impact of ARDS Etiology on the Failure of Noninvasive Ventilation and 28-Day Mortality: A Multicenter Prospective Observational Study

2021 ◽  
Author(s):  
Weiwei Shu ◽  
Shuliang Guo ◽  
Fuxun Yang ◽  
Bicui Liu ◽  
Zhongxing Zhang ◽  
...  
Keyword(s):  
Observational Study ◽  
Noninvasive Ventilation ◽  
Prospective Observational Study ◽  
Distress Syndrome ◽  
Cox Regression ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Propensity Matching ◽  
Multicenter Prospective Observational Study

Abstract Background: The failure rate of noninvasive ventilation (NIV) remains high in patients with acute respiratory distress syndrome (ARDS). The etiology of ARDS may play an important role in NIV failure.Methods: A multicenter prospective observational study was performed in 17 ICUs in China from September 2017 to December 2019. ARDS patients who used NIV as a first-line therapy were enrolled. The etiology of ARDS was recorded at study entry. Results: A total of 306 patients were enrolled. Of the patients, 146 were classified as having pulmonary ARDS (ARDSp) and 160 were classified as having extrapulmonary ARDS (ARDSexp). NIV improved PaO2/FiO2 from initiation to 24 h of NIV in both groups. However, it improved more slowly in patients with ARDSp than in those with ARDSexp (interaction effect: p < 0.01). ARDSp patients experienced more NIV failure (55% vs. 28%; p < 0.01) and higher 28-day mortality (47% vs. 14%; p < 0.01). The multivariate Cox regression also showed that ARDSp was independently associated with NIV failure (hazard ratio [HR] = 2.81, 95% confidence interval [CI]: 1.89-4.18) and 28-day mortality (HR = 7.49, 95% CI: 4.32-13.01). After propensity matching, 62 patients remained in each group. The baseline data were comparable between the two groups. ARDSp was still independently associated with NIV failure and 28-day mortality (HR = 2.62, 95%CI: 1.49-4.61; and 5.70, 2.59-12.55, respectively). Sensitivity analysis also confirmed these results. Conclusions: Among ARDS patients who used NIV as a first-line therapy, ARDSp was associated with slower improvement in oxygenation, more NIV failure, and higher 28-day mortality than ARDSexp.

scholarly journals Progress and Challenges of Integrated Drug Efficacy Surveillance for Uncomplicated Malaria in Thailand

2021 ◽  
Author(s):  
Prayuth Sudathip ◽  
Aungkana Saejeng ◽  
Nardlada Khantikul ◽  
Thannikar Thongrad ◽  
Suravadee Kitchakarn ◽  
...  
Keyword(s):  
System Integration ◽  
Treatment Guidelines ◽  
Drug Efficacy ◽  
Fiscal Year ◽  
Efficacy Rate ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
History Of

Abstract BackgroundIntegrated drug efficacy surveillance (iDES) was formally introduced nationally across Thailand in fiscal year 2018 (FY2018), building on a history of drug efficacy monitoring and interventions. According to the National Malaria Elimination Strategy for Thailand 2017–2026, diagnosis is microscopically confirmed, treatment is prescribed, and patients are followed up four times to ensure cure.MethodsRoutine patient data were extracted from the malaria information system for FY2018–FY2020. Treatment failure of first-line therapy was defined as confirmed parasite reappearance within 42 days for Plasmodium falciparum and 28 days for Plasmodium vivax. The primary outcome was the crude drug efficacy rate, estimated using Kaplan–Meier methods, at day 42 for P. falciparum treated with dihydroartemisinin-piperaquine plus primaquine, and day 28 for P. vivax treated with chloroquine plus primaquine; day 60 and day 90 efficacy were secondary outcomes for P. vivax.ResultsThe proportion of patients with outcomes recorded at day 42 for P. falciparum malaria and at day 28 for P. vivax malaria has been increasing, with FY2020 follow-up rates of 61.5% and 57.2%, respectively. For P. falciparum malaria, day 42 efficacy in FY2018 was 92.4% (n = 249), in FY2019 93.3% (n = 379), and in FY2020 98.0% (n = 167). P. falciparum recurrences occurred disproportionally in Sisaket Province, with day 42 efficacy rates of 75.9% in FY2018 (n = 59) and 49.4% in FY2019 (n = 49), leading to an update in first-line therapy to pyronaridine-artesunate at the provincial level, rolled out in FY2020. For P. vivax malaria, day 28 efficacy was 98.5% in FY2018 (n = 2,048), 99.1% in FY2019 (n = 2,206), and 99.9% in FY2020 (n = 2,448), and day 90 efficacy was 94.8%, 96.3%, and 97.1%, respectively.ConclusionsIn Thailand, iDES provided operationally relevant data on drug efficacy, enabling the rapid amendment of treatment guidelines to improve patient outcomes and reduce the potential for the spread of drug-resistant parasites. A strong case-based surveillance system, integration with other health system processes, supporting biomarker collection and molecular analyses, and cross-border collaboration may maximize the potential of iDES in countries moving towards elimination.

Outcomes of patients with metastatic colorectal carcinoma (MCRC) treated with first and second line chemotherapy at a multicenter cancer clinic

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13529-13529
Author(s):  
H. J. Lim ◽  
C. Lohrisch ◽  
C. Kollmannsberger ◽  
S. Gill ◽  
H. Kennecke ◽  
...  
Keyword(s):  
Median Number ◽  
Second Line ◽  
First Line ◽  
Related Factors ◽  
Second Line Chemotherapy ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Group B ◽  
Line Chemotherapy

13529 Background: In British Columbia (BC), FOLFIRI and FOLFOX were approved for the treatment of MCRC in 2002. The effect on survival of various treatment and patient related factors was determined for patients with MCRC treated with sequential doublet chemotherapy. Methods: Eligible patients received either FOLFOX or FOLFIRI first-line with a cross over to the alternative regimen for second-line therapy. Patient records were retrospectively reviewed for patient and disease characteristics, treatment, toxicity and survival. Analysis of survival was performed by the Kaplan-Meier method. Results: Between March 2002 and June 2004, 106 new patients met the criteria above. Sixty five patients were treated with a sequence of FOLFOX-FOLFIRI (Group A): 67% M, median age 57y, rectal 20%. Forty-one were treated with the sequence FOLFIRI-FOLFOX (Group B): 64% M, median age 58y, 27% rectal. Survival was statistically similar in both groups. Progression requiring second line chemotherapy within 4 weeks of a first line treatment was associated with inferior survival (13 months vs. 21 months (p<0.018). Grade 3 or 4 toxicity was experienced in 27.5% of the patients treated with FOLFOX and 22% of the patients treated with FOLFIRI. Conclusions: In the general population with MCRC, the median survival achieved with sequential doublet therapy is consistent with that reported in clinical trials. A superior sequence was not identified. The median number of first line chemotherapy cycles with FOLFOX and FOLFIRI was similar, reflecting the general clinical practice in BC to give 10 - 12 cycles of therapy followed by a planned break. Patients who required initiation of second line chemotherapy within 4 weeks of stopping the first line therapy experienced an inferior prognosis. Univariate and multivariate analysis showed no significance of sex, age, site (colon versus rectal), and ECOG status as predictive factors. [Table: see text] No significant financial relationships to disclose.

Next Generation Sequencing (NGS) to reveal mutations in IDH1 and its effect on patient (pt) outcomes in advanced biliary tract cancer (aBTC) who received gemcitabine and cisplatin (GC).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 287-287
Author(s):  
Daniel H. Ahn ◽  
Chul Ahn ◽  
Apurva Jain ◽  
Sameh Mikhail ◽  
Christina Sing-Ying Wu ◽  
...  
Keyword(s):  
Somatic Mutations ◽  
Cox Regression ◽  
Progression Free Survival ◽  
Idh1 Mutation ◽  
Cancer Center ◽  
First Line ◽  
Free Survival ◽  
First Line Therapy ◽  
Line Therapy ◽  
Dismal Prognosis

287 Background: aBTC is uncommon and has a dismal prognosis with limited therapeutic options. First-line therapy for untreated aBTC is GC, with no approved therapies in the refractory setting. To assess for tumor-specific genetic variants that affect outcomes in patients (pts) who received GC in aBTC, we performed NGS in pts treated with who received GC as first-line therapy. Methods: Archival formalin-fixed, paraffin-embedded samples from pts with mBTC from Ohio State University and MD Anderson Cancer Center who received GC in the first-line and underwent NGS as part of routine care. 315 cancer-related genes plus select introns from 28 genes altered in solid tumors were included in the NGS panel. Univariate Cox regression model was used to determine the association between gene mutations with progression free survival (PFS) and (OS). Results: 80 evaluable pts with aBTC treated with first-line GC chemotherapy underwent successful genomic profiling. A total of 414 cancer-specific mutations were identified, where 49 (12%) genes had mutations with > 5% frequency. 17 of the 49 were known mutations. From the comprehensive analysis, somatic mutations in IDH1 (11 of 80 pts; 13%) (HR 0.31; p = 0.035) was associated with improved overall survival (OS) and progression free survival (PFS). Pts wild type for IDH1 had a median OS of 17.7 months and PFS of 4.5 months, while those with an IDH1 mutation had a median OS that was not reached and an improved PFS of 5.7 months. Conclusions: Somatic mutations in IDH1 were associated with improved clinical outcomes in pts with aBTC who received GC as first-line therapy which is consistent with other solid tumor malignancies. IDH1 is a therapeutic target of interest, where future prospective studies will be necessary to validate the predictive utility and its relevance in pt outcomes in aBTC.

Treatment-free survival (TFS) after discontinuation of first-line nivolumab (NIVO) plus ipilimumab (IPI) or sunitinib (SUN) in intention-to-treat (ITT) and IMDC favorable-risk patients (pts) with advanced renal cell carcinoma (aRCC) from CheckMate 214.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 564-564 ◽  
Author(s):  
David F. McDermott ◽  
Brian I. Rini ◽  
Robert J. Motzer ◽  
Nizar M. Tannir ◽  
Bernard Escudier ◽  
...  
Keyword(s):  
Risk Groups ◽  
First Line ◽  
Free Survival ◽  
Intention To Treat ◽  
Poor Risk ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Risk Patients ◽  
Clinical Trial Information

564 Background: TFS characterizes the antitumor activity of immuno-oncology agents after treatment discontinuation. In CheckMate 214, pts with IMDC intermediate/poor-risk aRCC who discontinued first-line NIVO+IPI experienced significantly longer TFS than those who discontinued SUN (McDermott et al, ESMO 2018). Here, we continue the analysis of TFS from CheckMate 214 in ITT and IMDC favorable-risk pts. Methods: Pts with previously untreated, predominantly clear cell aRCC were randomized 1:1 to intravenous NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks for 4 doses followed by NIVO 3 mg/kg every 2 weeks, or oral SUN 50 mg daily for 4 weeks on, 2 weeks off (6-week cycles). TFS was defined as the time from protocol therapy cessation to the start of subsequent systemic anticancer therapy or death, whichever occurred first. TFS in pts who discontinued NIVO+IPI or SUN was compared using Kaplan–Meier methods and log-rank tests. This analysis was conducted for all ITT (NIVO+IPI, 550; SUN, 546) and IMDC favorable-risk (NIVO+IPI, 125; SUN, 124) pts in CheckMate 214. Results: Among 463 NIVO+IPI and 477 SUN ITT pts who discontinued protocol therapy, the median TFS was 3.0 months with NIVO+IPI vs 1.3 months with SUN (HR [95% CI]; 0.54 [0.46–0.62]; P<0.0001); the TFS rates 2 years post-discontinuation were 21% vs 7%, respectively. In IMDC favorable-risk pts, 111 and 94 pts discontinued from NIVO+IPI and SUN, respectively. TFS in IMDC favorable-risk pts was also significantly longer with NIVO+IPI vs SUN (median, 6.3 vs 1.1 months; HR [95% CI]; 0.47 [0.34–0.65]; P<0.0001). The TFS rates 2 years post-discontinuation in favorable-risk pts were 29% for NIVO+IPI vs 13% for SUN. Conclusions: Similar to the TFS benefit seen in intermediate/poor-risk pts with aRCC, first-line therapy with NIVO+IPI resulted in reduced need for second-line therapy in ITT and IMDC favorable-risk pts compared with SUN. The durable TFS benefit across risk groups despite discontinuation of therapy provides further evidence of the encouraging benefit-risk profile of NIVO+IPI over SUN in pts with previously untreated aRCC. Clinical trial information: NCT02231749.

Survival outcomes with the use of immunotherapy (IO) in patients (pts) with metastatic non-small cell lung cancer (mNSCLC) at a large hybrid cancer institute.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21192-e21192
Author(s):  
Joanna Alyse Young ◽  
Christina Clarkson ◽  
Jiaxian He ◽  
Daniel Slaughter ◽  
Daniel Ernest Haggstrom ◽  
...  
Keyword(s):  
Real World ◽  
Smoking Status ◽  
Driver Mutations ◽  
First Line ◽  
Cox Models ◽  
First Line Therapy ◽  
Line Therapy ◽  
Kaplan Meier ◽  
Treatment Type ◽  
Former Smokers

e21192 Background: Landmark trials have shown increased survival in pts who receive IO for NSCLC as compared to chemotherapy (chemo). Median overall survival (mOS) ranged from 17-26 months (mo); however, mOS in several published “real-world” retrospective studies are lower, ranging from 8-12 mo, with about 4-5 months on IO treatment. We sought to define mOS of pts with mNSCLC who received IO as monotherapy or in combination with chemo as first line therapy at Levine Cancer Institute. Methods: We retrospectively reviewed 315 adult pts with mNSCLC without driver mutations diagnosed between 2016 and 2019. The Kaplan-Meier method was used to estimate and compare OS between IO and IO + chemo. Univariate and multivariate Cox models were used to evaluate risk factors (RF) for OS. RFs considered included age, sex, race, smoking status, histology, first-line treatment type, and metastatic (mets) sites. Results: Baseline pt characteristics were: 40% female, 77% white, 20% Black, 34% current smokers and 60% former smokers. Median age was 69 years (45-88) in pts receiving IO alone and 63 years (28-84) in pts receiving IO + chemo. Tumor characteristics were: 76% adenocarcinoma and 17% squamous cell carcinoma. PD-L1 TPS distribution was: 39% for 0%, 22% for 1-49%, and 39% for ≥50%. Distribution of mets was 10% adrenal, 40% bone, 30% brain, 14% liver, 31% lung. mOS for pts receiving IO and IO + chemo as first line therapy was 17 and 14.8 mos, respectively (P = .209). Median duration of IO received was 4.25 months (0 to 43.6). mOS as stratified by PD-L1 TPS was 14.5 mos for PD-L1 0%, 13.3 mos for PD-L1 1-49%, and 19.5 mos for PD-L1 ≥50% (P = .163). OS was significantly different between IO and IO + chemo after adjusting for age. No OS differences were seen between white and Black or between all pts vs pts with brain mets (brain-specific interventions not reviewed). The table summarizes significant findings only (P < 0.05). Conclusions: Pts with mNSCLC treated first-line with IO either alone or with chemo at Levine Cancer Institute lived longer than those in similar published “real-world” cohorts. Median OS was highest in patients with PD-L1 TPS ≥50%, although not statistically significant. While not unusual to identify worse outcomes in those with bone and liver mets, interestingly brain metastasis was not associated with worse survival. In this cohort, when adjusted for age, IO alone trends toward improved survival. Although there was no OS difference based on race, further investigation will seek to uncover any other disparities contributing to outcomes, such as insurance status and zip code mapping. To our knowledge, this provides the largest analysis of this patient population outside of a clinical trial.[Table: see text]

Genetic Aberrations and Response to Fludarabine as First Line Treatment in a Serie of B-CLL Patients.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2131-2131
Author(s):  
Pilar Giraldo ◽  
Araceli Rubio-Martinez ◽  
Valle Recasens ◽  
Mikel Valganon ◽  
Paz Latre ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Genetic Alterations ◽  
Fisher Exact Test ◽  
Line Treatment ◽  
First Line ◽  
Genetic Aberrations ◽  
First Line Therapy ◽  
Line Therapy ◽  
First Line Treatment

Abstract Background: Genetic factors have been established in the recent years as the most important independent predictors of disease progression and survival in patients with B-chronic lymphocytic leukaemia (B-CLL). Fludarabine is an approved first-line treatment for B-CLL, which achieves superior remission rates than traditional therapies. The drug is equally effective in early and advanced disease and in younger and elderly patients with B-CLL but different results have been found in patients with cytogenetic aberrations as methylation in the TP53 promoter Aims: To evaluate the response to Fludarabine as first-line therapy in B-CLL patients with advanced stages. Patients and methods: In the study 55 B-CLL patients were enrolled. The diagnosis was established based on standard morphologic and immunophenotypic criteria, and classified on high clinical risk category Rai stage III/IV treated with Fludarabine (25 mg/m2 daily for 5 days IV in a 28-day cycle) as first-line therapy from January 00 to December 03. Response was evaluated after 4 cycles of therapy and in those patients which had not achieved complete remission (CR) two additional cycles were administrated. Criteria for response were established using the revised 1996 NCIWG. FISH studies were performed using the probes LSI p53 (17p13), LSI D13S25 (13q14), CEP 12 and ATM gene (11q22). The sequences of the IGVH genes were determined in cDNA of the patients. Responses to therapy, time to progression disease and overall survival were available to analyse in 41 patients. Association was studied using contingence tables followed by Fisher exact test and to evaluate survival by acturial method of Kaplan Meier and Cox regression. Results: Mean age 64 (36.9–83.9), female 53.7%. 75% of patients presented genetic aberrations associated with worse prognosis: del (17p) and/or del (11q) (45%). No-mutated IGVH genes (57%). Response: 83.5% of patients achieved response (CR 47.8%). Related to genetic aberrations the responses were: 55.5% in patients with del(17p), 75.0% del(11q), 100% +12, 88.8% del(13q) and 100% of patients without genetic alterations showed response to Fludarabine. The 48.8 % of patients developed progression of disease with mean duration of the response of 15.1 months. Related to genetic aberrations the progression was over 81% of patients with genetic aberrations versus 55.5% without genetic alterations (p=0.044). The overall survival was 68.0 months. 34.1% of patients are alive in CR, 36.6% are alive with stable disease 7.3 % are alive with disease in progression and 22.0 % have died. Conclusions: A high response to Fludarabine in first line therapy was observed, however only 55.5% of patients with del(17p) showed response. Patients with genetic aberrations had higher significant rate of progression in comparison with those containing normal genotypes.

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