Prognostic impact of serum cytokeratin 19 fragments in patient with metastatic urothelial cancer (mUC) treated with first-line chemotherapy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 473-473
Author(s):  
Yuki Endo ◽  
Go Kimura ◽  
Jun Akatsuka ◽  
Masato Yanagi ◽  
Hikaru Mikami ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Urothelial Cancer ◽  
Cytokeratin 19 ◽  
Intermediate Risk ◽  
Line Treatment ◽  
First Line ◽  
Poor Risk ◽  
Metastatic Urothelial Cancer ◽  
First Line Treatment

473 Background: Even today, when several immune checkpoint Inhibitors have been approved for the treatment of metastatic urothelial cancer (mUC), cytotoxic chemotherapy (CTC) still remains the mainstay for first-line treatment. We believe that the prognostic factors for the first-line CTC have become more important again and need to be re-analyzed. Current guidelines do not yet provide recommendations for any serum tumor markers in patients with mUC. Previous studies have shown that serum cytokeratin 19 fragments levels (sCK) were correlated with depth of tumor invasion and metastatic burden in patients with bladder cancer. In this study we evaluated whether sCK, and other clinical parameters could predict overall survival (OS) in patients with mUC treated with CTC. Methods: Two hundreds fifty two patients with mUC received CTC from December 2006 to 2016 at our institution. sCK had been measured in 128 patients at diagnosis of mUC. OS rate were analyzed by Kaplan–Meier curves and log–rank test. Multivariate analysis was carried out using the Cox hazards model. Tumor burden (TB) was measured based on Response Evaluation Criteria In Solid Tumor (version 1.1). Results: Of 128 patients, with median age of 72 (44-93), 36 (28%) had lung metastasis, 11 (9%) had bone metastasis, 10 (8%) had liver metastasis (LM). Ninety five (74%) patients received platinum based chemotherapy as a first-line treatment. During the median follow-up period of 19 (1-89) months, 72 patients (70%) had died. A 1-year (1y) OS was 51% and a 2y-OS was 36%. On univariate analysis, performance status (PS) (HR2.0, p<0.005), sCK (HR3.9, p<0.001), CRP (HR4.0, p<0.001), neutrophil-lymphocyte ratio (HR1.9, p<0.049), LM (HR2.0, p=0.042) and TB (HR2.4, p<0.001) were the significant prognostic factors for OS. On multivariate analysis, PS (HR2.0, 95%CI (1.05-3.85) p=0.036 ), sCK (HR3.1, 95%CI (1.3-8.3), p=0.011), and LM (HR3.0, 95%CI (1.06-6.98), p=0.022) were the independent prognostic factors for OS. Based on these 3 factors we divided patients into three groups, good risk (G, 0 factor), intermediate risk (I, 1 factor) and poor risk (P, 2-3 factors). There was a significant difference between the three groups. (G vs I: p<0.001, I vs P: p=0.001). Conclusions: PS, sCK, and LM were the independent prognostic factors for OS in patients with mUC receiving CTC. For the patients in good or intermediate risk with this score, early exposure of ICIs should be performed after CTCs. Treatment strategy should be changed in patients with poor risk since CTC is primary refractory in such population.

Comparison of bevacizumab versus pemetrexed in combination with platinum-based doublets in first-line treatment of advanced non-small cell lung cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18078-e18078 ◽  
Author(s):  
Augusto Akikubo Rodrigues Pereira ◽  
Sandro José Martins ◽  
Rafael Costa Lessa ◽  
Flavio Augusto Ismael Pinto ◽  
Debora De Melo Gagliato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Small Cell ◽  
Line Treatment ◽  
Small Cell Lung ◽  
Adrenal Metastases ◽  
First Line ◽  
Nonsquamous Nsclc ◽  
First Line Treatment

e18078 Background: First-line treatment of advanced nonsquamous non-small cell lung cancer (NSCLC) with platinum-based doublets, including pemetrexed (P) or bevacizumab (B), has achieved more than 12 months of survival. At the moment, there are no phase III head-to-head comparisons of these combinations. Methods: We retrospectively analyzed, from 05/2007 to 02/2011, in a single institution, all pts with stage IIIB or IV nonsquamous NSCLC treated with B or P combined with platinum compounds in first-line treatment to determine differences in OS, PFS, ORR and toxicity. We performed multivariate analysis to identify prognostic factors for survival. Results: Of the 82 pts included, 40 pts (48,8%) received carboplatin/paclitaxel or cisplatin/gemcitabine combined with B (BEV group), while 42 pts (51,2%) received cisplatin or carboplatin combined with P (PEM group). BEV had significantly fewer pts with age > 70 years (p=0,01) and CNS metastases (p<0,001) than PEM. Maintenance therapy was administered in 65,0% and 52,4% of pts in BEV and PEM groups, respectively (p=0,17). Significantly more pts in BEV received second-line treatment (72,5% vs. 52,4%; p=0,04) than in PEM, prevailing P as drug of choice (79,3%). ORR (60,0% vs. 35,7%; p=0,04) and median survival (26,4 vs. 16,4 months; p=0,009) were significantly superior for BEV. Median PFS were not different between BEV and PEM (10,5 vs. 7,7 months; p=0,06). In multivariate analysis, ECOG 2 (p=0,005), bone (p=0,01) and adrenal metastases (p=0,005) were independent prognostic factors for worst survival, while treatment with BEV did not reach statistical significance (p=0,07). Grade 3-4 neutropenia (27,5% vs. 9,5%; p=0,03) and neuropathy (17,5% vs. 0%;p=0,005) were more frequent in BEV. Conclusions: First-line treatment of advanced nonsquamous NSCLC patients with platinum-based doublets combined with B resulted in better ORR and higher rate of toxic effects as compared with P-based regimens. ECOG 2, bone and adrenal metastases were independent prognostic factors for poor survival. Although there was a survival benefit at univariate analysis, use of B combination was not an independent prognostic fator.

Association of hypothyroidism with improved outcomes in first-line treatment of renal cell carcinoma with sunitinib.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 466-466 ◽  
Author(s):  
Flavio Augusto Ismael Pinto ◽  
Augusto Akikubo Rodrigues Pereira ◽  
Maria Nirvana Formiga ◽  
Marcello Ferretti Fanelli ◽  
Ludmilla T. D. Chinen ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Prognostic Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Kinase Inhibitor ◽  
Univariate Analysis ◽  
Intermediate Risk ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

466 Background: Sunitinib, a multitarget tyrosine-kinase inhibitor, has become a standard of care for first-line low and intermediate risk metastatic renal cell carcinoma (mRCC). Sunitinib-induced hypothyroidism and hypertension have been correlated with better outcomes in those patients. Methods: Fifty patients with mRCC, treated in the first-line with sunitinib, were retrospective analyzed at one brazilian institution, for overall survival (OS), progression free survival (PFS), overall response rate (ORR) and toxicity. We evaluated clinical and laboratory parameters, such as hypothyroidism (TSH level > 5,5 mIU/L) and hypertension, to identify prognostic factors. Results: The median age of patients was 58 years (range: 37-73 years), 82% were male, 54% were ECOG 0 or 1, and 76% were classified in low or intermediate risk. Nefrectomy was performed in 96% of cases. Lung and bone were the most common sites of metastases. The incidence of hypothyroidism and hypertension during treatment were 40% and 34%, respectively. ORR for the entire population was 40% and it was statistically superior in patients that developed hypothyroidism during treatment (90% vs. 20%; p<0,0001). Median survival and PFS were 21.7 months (10.65-17.70 months, 95% CI) and 14.2 months (15.77-27.58 months, 95% CI), respectively. In univariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001), hypothyroidism (p<00001) and hypertension (p=0,001) were associated with OS. In multivariate analysis, ECOG (p<0,0001), MSKCC criteria (p<0,0001) and hypothyroidism (p<00001) were independent prognostic factors for OS. The most common severe adverse events (G3-4) were asthenia (14%), diarrhoea (6%), neutropenia (14%), thrombocytopenia (10%), hand-foot syndrome (6%) and hypertension (8%). Conclusions: Efficacy in survival and toxicity profile of sunitinib in first-line treatment of mRCC in patients out of clinical trials were comparable to prior studies. Hypothyroidism, MSKCC criteria and ECOG were independent prognostic factors for survival.

Autologous Stem Cell Transplantation in Patients with Mantle Cell Lymphoma: A Retrospective Study of the Geltamo Group (1994-2011)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3980-3980
Author(s):  
Ana García-Noblejas ◽  
Eulogio Conde ◽  
Alejandro Martín ◽  
María Jesús Vidal ◽  
Rafael Rojas ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Cell Lymphoma ◽  
Disease Status ◽  
Line Treatment ◽  
First Line ◽  
Kaplan Meier ◽  
Mantle Cell ◽  
First Line Treatment

Abstract INTRODUCTION Autologous stem cell transplantation (ASCT) is one of the current treatment options for first-line treatment of mantle cell lymphoma (MCL) in young and fit patients in first complete response (CR). Nevertheless its role in less than CR, after intensive chemotherapy schemas or as consolidation after salvage regimens has not been established. AIM To analyze the impact of patient and treatment characteristics on outcome of MCL patients treated with ASCT. METHODS Retrospective analysis of MCL patients treated with ASCT and registered in the GELTAMO database from 1994 to 2011. An outcome up-date was performed on December 2013. The study was approved by local ethical committees. Statistical analysis was performed using SPSS 15.0. RESULTS Two hundred and forty eight patients were registered from the GELTAMO database. Patients’characteristics : median age was 55 years old (range 21-70 y), 70% male. One hundred and fifty eight patients (68%) were transplanted in CR, 125 were in first CR (79% of all CR) and 33 in second or third CR (21%). Fifty two patients (22%) were transplanted in first partial response and 15 (6%) with chemosensitivity disease after relapse. Only 8 patients (3%) were transplanted with refractory disease. Response : forty-eight out of 75 patients (64%) without CR at ASCT converted to CR after transplant. Survival: Sixteen percent of patients were lost to follow-up one year after transplantation. Median follow-up for alive patients was 47 months (range 0-245 months). Progression free survival for patients transplanted in first CR was 45 months (CI95%: 33-56 months), for patients transplanted in first partial response (PR) was 28 months (CI95%: 15-21months) and for patients transplanted in other response was 19 months (CI95%: 12-26 months). In the whole series, median overall survival (OS) from transplantation was 69 months (CI95% 51-87 months) and for those patients transplanted in first CR was 98 months (CI95% 67-130 months). When patients without CR before transplant are analyzed separately, those who achieved CR after transplantation have better PFS (38 vs 10 months, p<0.001) and OS (74 vs 16 months, p<0.001) than others. Treatment related mortality was 4%. We analyzed the variables that could be associated with PFS and OS. We considered age (≤60 vs >60), ECOG (<2, ≥2), IPI (<2, ≥2), status at transplant (1st CR vs others), conditioning with TBI and HDAC in first line treatment. In univariate analysis, ECOG (p=0.04) and status at transplant (p=0.01) were the variables associated with PFS. For OS, the same variables resulted significant (p<0.001 and p=0.07, respectively) and also, HDAC emerged as significant variable associated with outcome. (p=0.05). In multivariate analysis, ECOG and status at transplant remained as independent prognostic factors for PFS while ECOG and HDAC in first line had impact for OS, see Table 1. Table 1. Variables identified as independent prognostic factors for PFS and OS in multivariate analysis. PFS OS p RR (95% CI) p RR ECOG 0.01 3.6 (1.3-9.9) 0.04 4.5 (1.6-12.5) Status at trasplant 0.03 1.4 (1-2) 0.09 (ns) ---- HDAC at 1st line 0.7 (ns) ---- 0.014 0.5 (0.3-0.8) Afterwards, a survival analysis for PFS and OS was performed according to have received high dose AraC (HDAC) in first line treatment or not and disease status (DS) before ASCT (Table 2). Table 2. Survival analysis according to have received HDAC in 1st line treatment and disease status (DS) before ASCT DS before ASCT N Firts line treatment N PFS (CI95%)(Kaplan Meier) p OS (CI95%)(Kaplan Meier) p 1st CR 125 No HDAC 52 37 (22-51) 0.13 64 (37-91) 0.01 HDAC 72 56 (33-78) No reached 1st PR 52 No HDAC 35 33 (3-63) 0.59 61 (0-126) 0.9 HDAC 17 27 (18-37) 69 (46-92) ≠1st CR/PR 51 No HDAC 46 20 (13-27) 0.16 35 (5-66) 0.9 HDAC 5 11 (7-16) No reached CONCLUSION This retrospective study reproduces previous results published about the role of ASCT in MCL: ASCT consolidation in first CR induces high survival rates with a median PFS of 45 months and median OS of 98 months. Patients without CR after ASCT had a significant inferior outcome. ECOG < 2 and status at transplantation are crucial for PFS and first line treatment with AraC improves significantly OS, particularly in patients with first CR. Disclosures No relevant conflicts of interest to declare.

Progression-free survival as an endpoint for clinical trials in first-line metastatic urothelial cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 251-251
Author(s):  
Matt D. Galsky ◽  
Susanne Krege ◽  
Chia-Chin Lin ◽  
Noah M. Hahn ◽  
Thorsten Ecke ◽  
...  
Keyword(s):  
Phase Ii ◽  
Urothelial Cancer ◽  
Performance Status ◽  
Progression Free Survival ◽  
Line Treatment ◽  
Phase Ii Trials ◽  
First Line ◽  
Free Survival ◽  
Metastatic Urothelial Cancer ◽  
First Line Treatment

251 Background: Advances in the first-line treatment of metastatic urothelial cancer (UC) have proven elusive. The lack of appropriate intermediate endpoints to screen the activity of novel regimens may be a barrier to progress, particularly in this disease state characterized by relatively high response rates but short response durations. Progression-free-survival (PFS) at fixed time points may overcome several of the limitations of response rate-based endpoints, but would be further supported by establishing benchmarks and demonstrating a correlation between PFS and overall survival (OS). Methods: Data were pooled from eight phase II and III trials evaluating first-line cisplatin-based chemotherapy in metastatic UC. Landmark analyses for progression at 3, 6, and 9 months after treatment initiation were performed to minimize lead-time bias. A proportional hazards model was used to assess the utility of PFS for predicting OS. Results: 545 patients were included in the analysis. The median PFS was 7.75 months (95% CI, 7.06, 8.18) and the median OS was 12.35 months (95% CI, 10.97, 13.44). The results of the landmark analysis, adjusted for performance status ≥ 1 and presence of visceral metastases, is shown in the Table. By using the Fleischer model, the estimated correlation between PFS and OS was 0.86 (bootstrap standard error 0.001, 95% CI 0.83, 0.89). Conclusions: PFS at 3, 6, and 9 months predicted OS in this analysis of patients with metastatic UC treated with first-line cisplatin-based chemotherapy. This analysis provides benchmarks, and support, for the use of PFS as an endpoint for phase II trials screening the activity of novel regimens as first-line treatment for metastatic UC. [Table: see text]

Molecular Prognostic Factors in Acute Myeloid Leukemia (AML) Patients Receiving First Line Therapy with Azacytidine (AZA)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 482-482
Author(s):  
Judith Desoutter ◽  
Julie Gay ◽  
Céline Berthon ◽  
Lionel Ades ◽  
Jean Pierre Marolleau ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Gene Mutation ◽  
Prognostic Value ◽  
Line Treatment ◽  
First Line ◽  
Secondary Aml ◽  
Mutational Status ◽  
The Impact ◽  
First Line Treatment

Abstract BACKGROUND: AML in elderly patients, secondary AML and/or AML with complex karyotype respond poorly to conventional intensive chemotherapy (CT) and have a poor prognosis. In those patients, however, AZA can bring some benefit, especially in the absence of adverse cytogenetics, if WBC < 15 × 10⁹/L and performance status (PS) < 2 (Thepot, Am J Hemat, 2014; Pleyer Ann Hematol, 2014). Whether molecular findings can predict outcome in AML receiving first line AZA (as they do in AML receiving CT) is however unknown. PATIENTS AND METHODS: 96 AML patients who received between 2007 and 2012 first line treatment with AZA (75mg/m2/d x 7 d/4 weeks SC for a median of 7 cycles, range 1-33) in 8 French centers were retrospectively analyzed. Initial response was evaluated based on blood and marrow examination after 4 -6 cycles of AZA. We analyzed the impact on overall survival (OS) of conventional clinico-biological parameters, and molecular biology parameters including EVI1 expression, MLL-PTD, and the mutational status of 16 genes analyzed by next-generation sequencing (NGS) and Sanger sequencing: ASXL1, CEBPA, DNMT3A, EZH2, FLT3, IDH1, IDH2, NPM1, NRAS, KRAS, RUNX1, SF3B1, SRSF2, U2AF1, TET2, and TP53. RESULTS: Median age was 73 (range, 44-88). Median PS was 1 (range, 0-3). 55% patients had secondary AML, including post MDS or MPN AML (N=39), and therapy related AML (N=14). 64% of patients had high risk cytogenetics and only 14 normal karyotype. Median WBC was 3.87 G/L and 28 patients had WBC >10 G/L. Median platelets and Hb were 61 G/L and 9.25 g/dL respectively. 41 and 55 patients had marrow blasts < 30% and ≥ 30% respectively, and median circulating blast % was 15% (range, 0-95). The median number of somatic mutations per patient was 2 (range, 0-5). The most frequently mutated genes were TP53 (40%), TET2 (22%) and SRSF2 (19%), then DNMT3A (14%), ASXL1 (13.5%), IDH2 (11%) and RUNX1 (11%). EVI1 overexpression (defined stringently in this study as DD CT ≤ 8 EVI1/ABL) was found in 12 patients. Overall response rate was 29% (14% CR, 8% PR and 7% Cri), and median response duration was 9.4 months. Median OS was 10.9 months. In univariate analysis, the following factors were significantly associated with shorter OS: platelets and Hb below median (p<0.0001 and p=0.0007 respectively), PS≥2 (p=0.008), and circulating blasts as continuous variable (p=0.03) while WBC and cytogenetics had no significant impact. OS was significantly worse in patients with TP53 gene mutation (median 8.9 vs 12.3 months in unmutated cases, p=0.01). It tended to be worse for SRSF2 gene mutation (median 8.4 vs 11.5 months, p=0.16) and TET2 gene mutation (median 8.8 vs 11.7 months, p=0.20) and tended to be better in patients with EVI1 overexpression (median 16.1 vs 9.4 months in other patients, p=0.17), while the mutational status of ASXL1, DNMT3A, IDH2 and RUNX1 genes had no impact on OS. Median survival of patients with at least one mutation of TP53, TET2, SRSF2 genes, was 9.1 vs 14.8 months if the 3 mutations were absent (p=0.0008, figure A). In multivariate analysis (logistic regression according to the Wald method), higher PS (p=0.0061), lower Hb (p=0.0014), lower platelets (p=0.0139) higher % circulating blasts (p=0.0145) and presence of TP53, TET2 or SRSF2 mutation (p=0.0035) were associated with poorer OS. Due to the low number of patients with EVI1 overexpression, this parameter was not included in the multivariate analysis. However, the 7 patients with EVI1 overexpression without any poor prognostic mutation had a median OS of 25.1 months ,versus 8.8 in patients carrying TP53, TET2 and/or SRSF2 mutations and 12.6 months in remaining patients without EVI overexpression (p=0.022) (figure B). Figure 1 Figure 1. Figure 2 Figure 2. CONCLUSION: In this first analysis (to our knowledge) of the prognostic value of molecular factors in poor risk AML (55% secondary cases, 64% unfavorable karyotype) receiving first line treatment with AZA, mutations of the TP53 and to a lesser extent TET2 or SRSF2 genes were adverse prognostic factors, and added prognostic value to conventional clinical and hematological parameters. For TET2, the effect seemed different from the favorable prognosis observed in MDS treated with AZA (Itzykson, Leukemia, 2011; Sekeres, Blood, 2012). Surprisingly also, EVI1 overexpression, a poor prognostic factor in AML, seemed associated with better outcome with AZA treatment in the absence of any poor prognostic mutation Those findings will require confirmation in larger prospective series. Disclosures No relevant conflicts of interest to declare.

scholarly journals Waldenstrom's Macroglobulinemia and Overall Survival in Relation to Prognostic Factors and First Line Treatment: An Observational Study from Swedish Lymphoma Registry

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1805-1805
Author(s):  
Lena Brandefors ◽  
Beatrice Melin ◽  
Jack Lindh ◽  
Lundqvist Kristina ◽  
Eva Kimby
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Medical Records ◽  
Line Treatment ◽  
Monoclonal Immunoglobulin ◽  
First Line ◽  
Female Sex ◽  
Waldenström's Macroglobulinemia ◽  
First Line Treatment

Abstract Introduction: Waldenstrom's macroglobulinemia (WM) is a rare disease with a worldwide incidence of approximately 3-4 per million persons per year. The definition of WM includes presence of lymphoplasmacytic lymphoma (LPL) in bone marrow and IgM monoclonal immunoglobulin at any concentration (MI) in serum. LPL with nodal disease is mostly included in most epidemiological studies. In Sweden the age adjusted incidence for WM and LPL is high; 10.6 per million persons per year. The aim of this study is to describe the WM population in Sweden from a prospective nationwide population-based registry and to compare outcome in relation to prognostic factors and first line treatment. Methods and study population: Between January 1, 2000 and December 31, 2014, in total 1511 patients with WM/LPL were registered in the Swedish Lymphoma Registry (SLR). The diagnosis was verified from medical records in 1135 patients and were classified as following; WM 978 (86.2 %), LPL 124 (10.9 %), other diagnosis 15 (1.3 %), and unclassified 18 (1.6 %). Results: For the WM population (n = 978) the median age at diagnosis was 73 years (range: 29 to 94) with a male/female ratio of 1.5 and with no difference in age between males and females. Only 26 patients (2.7 %) were diagnosed below 50 years of age and 718 (73.4 %) patients were older than 65 years. The median size of the IgM monoclonal immunoglobulin (MI) in 960/978 patients at diagnosis was 19 g/l, and only 33 (3.4 %) patients had an IgM MI >70 g/l. The most common IgM MI was of kappa type; 642/794 (81 %). Twenty-six (3 %) patients had biclonal immunoglobulins. The median overall survival (OS) for all WM patients was 96 months with a 3-years and 5-year OS of 78 % and 66 %, respectively. The OS has improved over the time. Significant prognostic factors for OS in newly diagnosed patients (symptomatic and asymptomatic) in univariate analysis were; age (p < 0.001), WHO performance status (PS) 1-4 (p < 0.001), B-symptoms (p < 0.001), elevated LDH (p < 0.001), haemoglobin ≤ 115 (p < 0.001), albumin ≤ 35 (p < 0.001), Beta-2-microglobuline (B2M) > 3 (p < 0.001), platelets ≤ 100 (p < 0.001), and lymphocytosis ≥ 5x109/l (p < 0.001), but not the size of the IgM MI (p = 0.36), IgM MI > 70 (p = 0.66), the light chain (kappa/lamda) (p = 0.32) or hypogammaglobulinemia. In multivariate analysis age (p > 0.001), elevated LDH (p = 0.01), PS 1-4 (p < 0.001), and haemoglobin ≤115 (p < 0.001) remained significant (B2M, platelets and lymphocytosis were excluded due to many missing values). Female sex emerged as a positive prognostic factor (p = 0.003). In Sweden is "watch and wait" (w&w) the recommended strategy in asymptomatic patients and w&w patients had a superior median OS compared to symptomatic patients, 101 and 77 months respectively. Approximately one fourth of the patients were symptomatic at diagnosis and data on first line treatment 0 - 3 months after diagnosis are available for 203 patients. Univariate and multivariate analyses on prognostic factors were performed separately for the patients with systemic therapies initiated 0 - 3 months after diagnosis (n = 203). Age (p < 0.001), PS 1-4 (p < 0.001), and haemoglobin ≤ 115 (p > 0.001) were significant prognostic factors in multivariate analysis. The size of the IgM MI (p = 0.87) or IgM MI > 70 (p = 0.58) was not significant prognostic factors. Rituximab was introduced in WM therapy in the years 2007/2008 and when including treatment with rituximab (single or in combination with chemotherapies) and treatment with chemotherapies in the multivariate analysis emerged rituximab (p = 0.005), female sex (p = 0.002) as positive prognostic factors and LDH (p = 0.002), albumin ≤ 35 (p = 0.045) as negative prognostic factors. Conclusion: The incidence of WM is higher in Sweden compared to the worldwide incidence. In this large unselected nation-wide WM population with trough medical records confirmed diagnosis, earlier known prognostic risk factors were confirmed, except the size of the IgM MI. Treatment with rituximab was independently associated with improved OS in multivariate analysis. The OS had improved over the time, the reason for that is unclear but one explanation could be the introduction of rituximab to the treatment. Disclosures Kimby: Gilead: Honoraria, Other: honoraria for educational lecture in meeting sponsored by Gilead; Jansen: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lecture at educational session; Celgene: Other: Honoraria for lecture. educational meeting; Pfizer: Other: Research grant; Roche: Other: Honoraria for lecture in educational meetings.

scholarly journals Clinical and Biological Characteristics and Outcomes of Richter Transformation : A French Multicenter Study from the Filo Group

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4112-4112
Author(s):  
Charline Moulin ◽  
Romain Morizot ◽  
Thomas Remen ◽  
Hélène Augé ◽  
Florian Bouclet ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Intermediate Risk ◽  
Line Treatment ◽  
First Line ◽  
Advisory Committees ◽  
Long Term Survivors ◽  
First Line Treatment

Introduction: About 2 to 10% of patients (pts) diagnosed with Chronic Lymphocytic Leukemia (CLL) develop diffuse large B-cell lymphoma (DLBCL, so-called Richter transformation (RT)) over long-term follow-up. The outcomes of pts with RT are variable and poorly understood and there is no consensus on the best therapeutic approach. The aim of this study was to analyze the clinical characteristics, outcomes and factors predictive of survival in a large series of RT from the French Innovative Leukemia Organization (FILO). Methods: Biopsy-confirmed RT (limited to DLBCL and excluding Hodgkin lymphoma) diagnosed from 2001 to 2018 were identified from eight FILO centers. Clinical and biological characteristics of CLL and RT at diagnosis, including cytogenetics, clonal relation with the pre-existing CLL, Epstein-Barr virus (EBV) status, cell of origin (COO) analyzed by immunohistochemistry and RT score (Tsimberidou AM et al, J Clin Oncol, 2006) were analyzed as well as treatment and outcomes. Overall survivals (OS) were defined as time from CLL and RT diagnosis to death from any cause and analyzed using the Kaplan-Meier method. Statistical analyses were performed with SAS version 9.4. Results: A total of 70 CLL pts who developed RT were identified. The median age at CLL diagnosis was 62 years old (range 35-82), and 50 (71.4 %) were male. The median time to transformation was 5.5 years (range 0 to 22 years), with 12 simultaneous diagnosis of CLL and RT. Prior to RT, 20 (29%) pts had not been treated for CLL, 50 received one (n=21) or more (n= 29) line of treatment ; 6 pts had received a novel agent (ibrutinib, idelalisib or venetoclax). The median age at RT diagnosis was 68 years old (range 42-88). All biopsies were centrally reviewed; 38/58 pts (66%) had elevated LDH (>1.5N) ; 35/65 pts (54 %) had bulky disease (≥ 5 cm); 10/54 (18.5%) pts had del(17p) or TP53 mutation ; 9/42 pts (21%) had a complex karyotype (at least 3 abnormalities). The CLL and RT were clonally related in 27/27 (100%) tested pts. COO by Hans algorithm was non germinal center B cell-like (GCB) in 26/28 pts (93%). EBV was positive or detected in 5/40 (12.5%) pts. The median of Ki67 positivity was 70% (range 30% to 100%). The RT score (based at RT diagnosis on ECOG performance status 2-4, LDH >1.5 x normal, platelets<100 x 109/L, tumor size >5 cm and >1 prior therapy for CLL) was : low risk in 17 pts (31%), low-intermediate risk in 10 pts (19%), high-intermediate risk in 14 pts (25%) and high risk in 14 pts (25%). The most common first-line treatment of RT was immunochemotherapy (n=57, 87%) including R-CHOP-like regimen (n=48, 73%). Autologous or allogeneic transplantation was performed for 7 pts (11%). Response to first-line treatment was complete or partial response in 26 pts (40%), and stable disease or progression in 39 pts (60%). After a median follow-up of 8 years, 51/64 pts (80%) have died. The main causes of death were progressive DLBCL (n=36, 71%), infection (n=8, 16%) or progressive CLL (n=2, 4%). The median OS of the cohort from CLL and RT diagnosis (Figure 1) were 7.8 years and 9.5 months, respectively. In univariate analysis, patients with TP53 disruption at CLL stage, low platelets count, elevated LDH, elevated beta2-microglobulin, high ECOG score, high RT score, EBV positivity and absence of response to first-line RT treatment had worse OS. The ECOG score, platelets count and TP53 disruption remain significant in multivariate Cox-regression. Last, we compared the clinical and biological parameters of two Richter groups defined as: (i) short-term survivors (<12 months, n = 34) and (ii) long-term survivors (>48 months, n = 18). Long survival was significantly associated with elevated platelets count, low LDH, low ECOG, low RT score and response to RT first-line treatment. Discussion: The clinical outcomes of RT patients is poor and novel treatment options are needed. However, a group of long-term survivors was identified, characterized by elevated platelets count, low LDH, low ECOG, low RT score and response to immunochemotherapy. Disclosures Leblond: Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Cymbalista:Janssen: Honoraria; Gilead: Honoraria; AstraZeneca: Honoraria; Sunesis: Research Funding; Roche: Research Funding; Abbvie: Honoraria. Guièze:Abbvie: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Roche: Honoraria. Broseus:Janssen: Honoraria; Gilead: Honoraria; Novartis: Research Funding. Feugier:gilead: Honoraria, Research Funding, Speakers Bureau; janssen: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau.

scholarly journals Predictive and Prognostic Factors in HCC Patients Treated with Sorafenib

Medicina ◽  
2019 ◽  
Vol 55 (10) ◽  
pp. 707 ◽  
Author(s):  
Oronzo Brunetti ◽  
Antonio Gnoni ◽  
Antonella Licchetta ◽  
Vito Longo ◽  
Angela Calabrese ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Factors ◽  
Prognostic Markers ◽  
Kinase Inhibitor ◽  
Quality Standard ◽  
Advanced Hepatocellular Carcinoma ◽  
Line Treatment ◽  
First Line ◽  
Advanced Hcc ◽  
First Line Treatment

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

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