Late Appearance of 14q32/IGH Translocation in Chronic Lumphocytic Leukemia

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2429-2429
Author(s):  
Francesco Cavazzini ◽  
Gian Matteo Rigolin ◽  
Lara Rizzotto ◽  
Antonella Bardi ◽  
Elisa Tammiso ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clonal Evolution ◽  
Fish Analysis ◽  
Line Treatment ◽  
First Line ◽  
Group 2 ◽  
First Line Treatment ◽  
14Q32 Translocation ◽  
Group 1

Abstract Abstract 2429 Up to 80% of Chronic Lymphocytic Leukemia (CLL) harbour clonal chromosome aberrations having important clinical implications (i.e. 13q deletion, +12, 11q/ATM and 17p/TP53 deletions). 14q32/IGH rearrangements were recently found in 6–19% of CLL patients and were associated with therapy-demanding disease and inferior outcome. Whereas evidence was provided that some of the classical aberrations, such as 11q-, 17p-, may appear late in CLL clinical history, no information is presently available concerning 14q32/IGH translocations. The aim of this study was i) to analyze the incidence of 14q32/IGH translocations occurring at clonal evolution in CLL, ii) to analyze the clinicobiologic significance of late-appearing 14q32/IGH translocations. One hundred-five CLL cases seen at our institution in a 10-year period were submitted to FISH analysis at diagnosis or before 1st line treatment as part of routine diagnostic workup. In 47 patients with indolent disease (untreated or treated with 1 line without relapse, group 1) FISH analysis was repeated after 48–96 months (median 72). In 58 relapsed patients who started 2nd line treatment (group 2), FISH was performed sequentially before administration of the 2nd line and before each subsequent line of therapy. These 105 patients fulfilled the following criteria: a) diagnosis of bona fide CLL based on morphology and immunophenotyping (CD5/CD19+, CD23+ as minimal requirement), b) clinical records available for review, c) successful FISH analysis at diagnosis and during follow-up. Those cases with t (11;14)(q13;q32)/CCND1-IGH or other 14q32/IGH translocations present at diagnosis were excluded from this study. Sequential FISH studies were performed in all patients on peripheral blood (PB) samples using commercially available probes for the identification of deletions at 13q14, 11q22/ATM, 17p13/TP53, of trisomy 12 and of 14q32/IGH translocations. In 10 patients bone marrow (BM) aspiration and/or lymph node (LN) biopsy were studied by FISH as well. The patients were treated at disease progression as defined by NCI criteria. Refractory disease was defined by stable disease or progressive disease during treatment or disease progression within 6 months of from antileukemic treatment using fludarabine alone or in combination with other agents. Time to chemorefractoriness was measured from date of first line treatment to date of refractoriness to fludarabine containing regimen or date of last follow-up. Overall survival was measured from diagnosis to date of last follow-up or death and from initiation of first line treatment to the date of death or last follow-up. At diagnosis 39% of the cases had 13q-, 14% had +12, 7% had 11q- and 3% had 17p-. A late-appearing 14q32/IGH rearrangement was not detected among 47 patients in group 1, whereas 7/58 cases (12,1%) in group 2 showed a 14q32/IGH break in 16–25% of the cells. These 7 patients had the following aberrations at diagnosis: 13q- and 11q- in 1 case, 13q- in 2 cases; 11q- in 1 case, +12 in 2 cases, no aberrations 1 case. The 14q32 translocation appeared after a median time of 64 months (range 51–91). It was associated with the appearance of 17p- in 3/7 cases with one of these presenting also biallelic del13q. In two cases paired BM or LN sample and PB samples were available for FISH studies and the appearance of IgH translocation in the BM or in the LN sample preceded its appearance in PB by 13–58 months. All 7 cases with late appearing 14q32/IGH translocation developed chemorefractoriness to fludarabine regimen with a median TTC of 27 months (range 12–40 months), as compared with a TTC of 67 months (range 1–143 months) in 51 treated patients who did not develop the 14q32 translocation (p=0.0002). Overall survival did not differ significantly either when measured from diagnosis or from 1st line treatment in 7 patients with 14q32 translocation as compared with the appropriate control. We arrived at the following conclusions: i) a late-appearing 14q32/IGH translocation occurred at a relatively high incidence (12,1%) in patients with relapsing disease and not in patients with stable disease, ii) this aberration involved a minority of cells and, in approximately half of the cases, it was associated with other aberrations, reflecting complex clonal evolution, iii) in 2 assessable cases it first appeared first in the BM or LN; iv) the appearance of 14q32/IGH translocation was associated with shorter TTC. Disclosures: No relevant conflicts of interest to declare.

Thalidomide–Containing Regimens Induce Recovery of Normal Immunoglobulins in Newly Diagnosed Patients with Multiple Myeloma; Recovery of Normal Immunoglobulins Improves Survival.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2738-2738
Author(s):  
Eirini Katodritou ◽  
Evgenia Verrou ◽  
Anastasia Banti ◽  
Dimitra Mihou ◽  
Vassiliki Gastari ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Time ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
Time To Progression ◽  
First Line ◽  
Group 2 ◽  
First Line Treatment ◽  
Group 1

Abstract Normal immunoglobulins, which are important for the host defense, are often decreased in Multiple myeloma (MM), either at the time of diagnosis or even after achieving response. Thalidomide, which is an immunomodulatory drug, in combination with other chemotheraputic drugs is effective for the treatment of newly diagnosed multiple myeloma (MM) patients, yielding 60–80% response rate. The purpose of this study was to examine, if the addition of Thalidomide to standard regimens, in newly diagnosed MM patients, induces recovery of normal immunoglobulins and whether this normalization has any impact on time to progression and overall survival. Two hundred twenty–six newly diagnosed symptomatic MM patients were evaluated. One hundred sixty–nine patients, 95 males and 74 females, with a median age of 66 years (range 29–90) who presented with normal immunoglobulins’ value below the minimum normal limit at the time of diagnosis, were selected for analysis. One hundred twenty-seven patients (group 1) received standard regimens not containing Thalidomide (93 received Vincristine /Adriamycin /Dexamethasone and 34 received Melphalan /Prednisone). Forty-two patients (group 2) received regimens containing Thalidomide (27 patients received Vincristine /Adriamycin /Dexamethasone /Thalidomide, 10 patients Dexamethasone /Thalidomide and 5 patients Melphalan /Prednisone /Thalidomide). All patients were evaluated after at least 4 cycles of treatment (median time of evaluation 6mo, range 4-8mo) for recovery of normal immunoglobulins (defined as the return of the normal immunoglobulins within the normal range). Statistical analysis was performed with the Pearson’s chi square test, Mann Whitney-U test and binary logistic regression analysis. The patients in both groups were well-balanced concerning age, sex, ISS score, B2-micriglobulin, creatinine and LDH (p<0.05). Recovery of normal immunoglobulins was achieved in 14,2% in group 1 and 33,3% in group 2 (p=0.006). The multivariate analysis, including age, ISS, type of myeloma and addition of Thalidomide in the first line treatment regimens, showed that the addition of Thalidomide in first line treatment was the only factor predicting for recovery of normal immunoglobulins (p=0.04). With a median follow up of 32mo (range 4–231mo), the median overall survival of patients in whom recovery of normal immunoglobulins was observed and of patients without any immunoglobulin recovery, was 35mo (SD=23mo) and 31mo (SD=31,6mo), respectively (p=0.004) and the median time to progression was 16mo (SD=23mo) and 6mo (SD=22mo), respectively (p=0.005). These results suggest that, Thalidomide-containing regimens used as first–line treatment, induce significant recovery of normal immunoglobulins compared to regimens without Thalidomide and that, the recovery of normal immunoglobulins overall, positively influences time to progression and overall survival. Conclusively, this study highlights the important role of normal immunoglobulins in MM biology and outcome and may suggest that the recovery of normal immunoglobulins could be possibly another criterion for defining complete remission.

The Addition of Thalidomide in Any Line of Treatment of Multiple Myeloma, Improves Overall Survival: Single Center Experience in 246 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4813-4813
Author(s):  
Eirini Katodritou ◽  
Evgenia Verrou ◽  
Anastasia Banti ◽  
Vassiliki Gastari ◽  
Dimitra Mihou ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Dose ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Group 2 ◽  
First Line Treatment

Abstract Thalidomide is effective for the treatment of either newly diagnosed or relapsed/refractory multiple myeloma (MM) patients. However, the contribution of Thalidomide to the overall survival in MM has not yet been clarified. The aim of this study was to examine, if the incorporation of Thalidomide either in first or in any line regimens, positively influences overall survival, in a large cohort of MM patients, with a long follow up. Two hundred forty-six newly diagnosed symptomatic MM patients, 139 males and 107 females, with a median age of 67 years (range 29–90) were studied. One hundred ninghty-two patients (group 1A) received regimens not containing Thalidomide as first line treatment (129 received Vincristine /Adriamycin /Dexamethasone, 58 received Melphalan /Prednisone and 5 received Dexamethasone). Fifty-four patients (group 2A) received regimens containing Thalidomide as first line treatment (32 patients received Vincristine /Adriamycin /Dexamethasone /Thalidomide 14 patients Dexamethasone /Thalidomide and 8 patients Melphalan /Prednisone /Thalidomide). One hundred-ninety patients received second or more than second line therapy. One hundred twenty-three patients received standard regimens not containing Thalidomide (group 1B) and 77, regimens containing Thalidomide (group 2B). The standard regimens in group 1B and 2B were similar to first line regimens. Totally, 100 patients received regimens containing Thalidomide at any time of the disease. Twenty and 8 patients in group 1A+1B and 2A+2B, respectively, received high dose therapy. The evaluated parameters, for predicting overall survival were: age, ISS score, creatinine, B2 microglobulin, LDH, Thalidomide-containing regimens in first line (group 2A) and in any line of treatment (group 2, A and B), time to response to first line treatment and quality of response (CR+PR versus less than PR). Cox regression was used for the univariate and multivariate analysis and Mann Whitney-U test and Pearson’s chi square test, for comparisons of patients’ characteristics. The median follow up was 31 months (range 1–231). Patients in both groups were well-balanced concerning age, sex, ISS score, B2-micriglobulin, creatinine and LDH (p<0.05). There was no statistical difference concerning the number of patients who proceeded to high dose therapy in both groups at any time of treatment (P>0.05). The univariate analysis showed that, age, ISS score, creatinine, B2 microglobulin, LDH, Thalidomide-containing regimens either in first or in any line of treatment and time to response to first line treatment, predicted for survival. The multivariate analysis demonstrated that age, ISS score and regimens containing Thalidomide in any line of treatment (group 2, A and B), independently predicted for overall survival (p<0.05). The median survival in the group 1 and 2 was 28mo (SD=35mo) and 34mo (SD=26mo), respectively (p=0.04). This study showed that, the incorporation of Thalidomide in any line of treatment, improves overall survival. Considering that the type of the standard regimens applied, either including or not Thalidomide, were similar and there was no statistical difference in the percentage of patients who underwent high dose therapy, between the two groups, these results produced by the analysis of a large cohort of newly diagnosed MM patients, with a long follow up offer important information about the impact of Thalidomide on the overall survival.

Impact of Second-Generation Tyrosine Kinase Inhibitors As Second Line Treatment for Patients with Chronic Myeloid Leukemia,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3780-3780 ◽  
Author(s):  
J Valentin Garcia-Gutierrez ◽  
Pilar Herrera ◽  
Lorena L Abalo ◽  
Maria Dolores Rey ◽  
Maria Calbacho ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Second Generation ◽  
Kinase Inhibitors ◽  
Salvage Treatment ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Group 2 ◽  
Group 1

Abstract Abstract 3780 Background: Imatinib has shown an outstanding improvement in the prognosis of chronic myeloid leukemia (CML) patients. Nevertheless, some of them have proven to be resistant or intolerant to imatinib. For these patients, second-generation tyrosine kinase inhibitors (TKIs) are available. These drugs may be indicated in different circumstances as primary or second resistance, suboptimal responses or intolerance.The real benefits of second-generation TKIs as salvage treatment are surely in dependence with the indication in each case and are, therefore, difficult to evaluate. Second-generation TKIs are being evaluated as first line treatment compared to imatinib with quite favourable outcomes so long, but have not yet been compared with a strategy combining imatinib followed by second-generation TKIs for patients with previous unfavourable responses. Aims: Evaluate the real benefit of second-generation TKIs in second line treatment for CML patients regardless of the indication for its use. Study groups and methods: We have studied 98 patients treated with imatinib as first tyrosin kinase inhibitor (TKI) in our centre. These patients have been classified according whether second-generation TKIs were available or not. Group 1 includes 60 patients treated since 2001 to 2005, when the only salvage treatment was an increased imatinib dose, chemotherapy or allogenic stem cell transplantation. Group 2 includes 38 patients treated since 2005 until today. In the second group second-generation TKIs (dasatinib or nilotinib) were used according to the indications mentioned above. Follow up period was 39 months and 32 months for group 1 and 2 respectively. Sokal risk index was high in 14% and 16%; intermediate 42 % and 40%; and low in 44% and 44 % for group 1 and 2 respectively. Results: The use of second-generation TKIs as second line resulted in significant benefit to patients in terms of responses. Complete cytogenetic responses (CCR) at any time were achieved in 73% and 86% for patients in group 1 and 2 (p=.09). Probability of the achievement of mayor molecular responses (MMR) was 42% vs 71% for group 1 and 2 respectively [p=.009; ratio=0.3 (0.1–0.7)]. Response rates at the last follow up for group 1 and 2 were: MMR: 33% vs 62%; CCR: 68% vs 94% and failure 32% vs 6% (p=.008). Progression free survival (including all the patients who started treatment) was 88% vs 94% for group 1 and 2 respectively. We found no correlation among responses and some prognostic factors (Sokal index, mutations at the TK domain or imatinib plasma levels). Imatinib doses were increased in 21 patients (35%) in group 1 (reasons for increasing doses were failure in 14 patients and suboptimal responses in 7 patients). 10 patients (26%) in group 2 received second-line TKIs as second line treatment (4 because imatinib failure, 3 by suboptimal responses and 3 due to intolerance). Conclussions: The use of second-generation TKIs as salvage has improved the responses of CML patients treated with TKIs. Once the second-generation TKIs has shown benefit compared to imatinib in first line treatment, this therapeutic strategy should be compared vs the use of imatinib followed of second-line TKIs for patients without optimal responses to imatinib. Disclosures: Montalban: Red Temática de Investigación Cooperativa en Cancer (RETICC): Research Funding; Asociación Española contra el Cancer: Research Funding.

First Line Treatment of Advanced Stage Hodgkin Lymphoma with Six Cycles of BEACOPPescalated Results in Superior Overall Survival Compared to ABVD: Results of a Network Meta-Analysis Including 10,011 Patients

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 551-551
Author(s):  
Peter Borchmann ◽  
Sven Trelle ◽  
Michaela Rancea ◽  
Heinz Haverkamp ◽  
Volker Diehl ◽  
...  
Keyword(s):  
Overall Survival ◽  
Initial Treatment ◽  
Meta Analysis ◽  
Treatment Strategies ◽  
Advanced Stage ◽  
Secondary Malignancies ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Abstract Abstract 551 Background: The best treatment strategy for advanced stage Hodgkin lymphoma (HL) is still a matter of debate. The German Hodgkin Study Group (GHSG) advocates aggressive treatment with BEACOPPescalated (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) to cure as many patients as possible with first-line therapy. However, BEACOPPescalated may expose patients to excessive toxicity. Treatment with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is supposed to be better tolerable. Proponents of primary ABVD therapy acknowledge a lower progression-free survival (PFS) compared to BEACOPPescalated. However, they argue that relapsing patients can subsequently be cured by high-dose chemotherapy resulting in comparable overall survival (OS). All trials evaluating these two strategies directly were either very small or included patient subgroups only. Although they congruently showed a significant PFS advantage for BEACOPPescalated, they were not powered to detect differences in OS, which obviously is the most important endpoint. Purpose: To assess the benefits and risks of different initial treatment strategies for adult patients with advanced stage HL and to provide patients and physicians with a high-level evidence for treatment decisions. Methods: Data Sources: We developed sensitive search strategies for CENTRAL, MEDLINE, and conference proceedings (searched from 01/1980 to 03/2012). Missing data was obtained from investigators. Study selection: Randomized trials that compared at least two out of twelve pre-defined chemotherapy regimens in adults with advanced stage HL. Two authors independently assessed studies for eligibility. Data extraction: We extracted data and assessed quality of trials in duplicate. The primary outcome was OS. Secondary outcomes included freedom-from-treatment failure (FFTF) and secondary malignancies. Data relates to four or five years of follow-up depending on the status of the trial. Data synthesis: We pooled data using network meta-analysis. Direct comparisons within trials were combined with indirect evidence from other trials by using a Bayesian random-effects model. Results are reported relative to ABVD with a hazard ratio (HR) >1 indicating superiority of ABVD. Results: 1,984 references were identified, of which 77 publications, reporting 14 trials, evaluating 11 different regimens were included. A total of 10,011 patients with 59,000 patient-years of follow-up were evaluable for the analyses of survival outcomes. Six cycles of BEACOPPescalated and 8 cycles of BEACOPP-14 were associated with the lowest risk for death of any cause (HR 0.38, 95%-CrI 0.20 to 0.75 and HR 0.43, 95%-CrI 0.22 to 0.86, respectively). Assuming a five-year survival rate of 89% for ABVD this would result in a 5-year survival benefit of 7% and 6% for 6 cycles of BEACOPPescalated and 8 cycles of BEACOPP-14, respectively (95%-CrI 3% to 9% and 2% to 9%, respectively). Eight cycles of BEACOPPescalated were also statistically significantly better as compared to ABVD but the effect was less pronounced. All other treatment strategies showed no statistically significant difference to ABVD. Similar results were obtained for FFTF. Between-trial heterogeneity was negligible in both analyses (tau-square 0.01 and 0.05, respectively). Overall, 327 secondary malignancy and 109 leukemia events accumulated over 57,529 patient-years of follow-up. Given the low number of events we were not able to accurately quantify the risk associated with each regimen; however, Stanford V might be associated with the lowest risk and C(M)OPP/EBV/CAD with the highest risk for secondary leukemias. Limitations: Some of the regimens were only evaluated in one trial. The number of secondary malignancies, especially leukemias, was low. Conclusions: The comparison of different first-line treatment strategies for advanced stage HL in this network meta-analysis shows a significant and relevant OS benefit for both, 6 cycles of BEACOPPescalated and 8 cycles of BEACOPP-14 over standard ABVD treatment. This analysis provides the currently best available evidence on OS of different initial treatment strategies for advanced stage HL patients and therefore adds valid and important information for both, patients and physicians. Disclosures: No relevant conflicts of interest to declare.

Single-agent docetaxel (TXT) as first-line treatment in metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11515-11515
Author(s):  
D. Guarneri ◽  
R. Ratti ◽  
A. Venturino ◽  
G. Addamo ◽  
Z. Coccorullo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Single Agent ◽  
Metastatic Breast ◽  
Line Treatment ◽  
First Line ◽  
Group 2 ◽  
Agent Treatment ◽  
First Line Treatment ◽  
Group 1

11515 Background: Historically anthracyclines have been considered the most active agents in metastatic breast cancer (MBC). Docetaxel (TXT) has challenged this belief. Aims: Evaluate response rates, toxicity and time to progression in patients with MBC receiving single agent TXT as first line treatment. Methods: MBC patients received first line single agent treatment according to one of the following schedules: TXT 35 mg/m2 iv weekly for 6 wks q 8 wks (Group 1) or TXT 100 mg/m2 iv day 1 q 3 weeks (Group 2). Adjuvant chemotherapy was FAC (600,50,600) day 1 q 21 days for 6 courses in all cases so treated. Results: Conclusions: It appears that results with single agent TXT obtained in clinical practice are comparable to those reported in Phase II-III trials (Group 1 and Group 2, respectively ) using the same regimens. [Table: see text] No significant financial relationships to disclose.

Association of progression free survival with the timing of genomic testing in non-small cell lung cancer: Evidence from the GuardantInform clinic-genomic database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21143-e21143
Author(s):  
Mark D. Hiatt ◽  
Junhua Yu ◽  
Nicole Zhang ◽  
Amy McNeal ◽  
Julie Kaylor ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Progression Free Survival ◽  
P Value ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Egfr Tki ◽  
First Line Treatment ◽  
Group 1

e21143 Background: The clinical utility of ctDNA analysis for biomarker identification in advanced non-small cell lung cancer (NSCLC) has been established, supporting clinical adoption of this testing modality. All FDA-approved, immune-checkpoint inhibitor (ICI) immunotherapies require the prerequisite of negativity for ALK rearrangement and EGFR mutation, or prior toxicity or progression on oral therapies targeting mutations in these genes. Despite these recommendations and support from the American Society of Clinical Oncology and National Comprehensive Cancer Network, broad-panel marker testing for targeted therapy options in NSCLC continues to be underperformed. Data are even limited on when those tests are typically conducted and the effects of timing on the treatment outcomes. Methods: The GuardantINFORM™ clinic-genomic database was interrogated for patients over the age of 18 having a Guardant360 test positive for EGFR mutations of L858R or exon 19 after 2016 and known to have a confirmed diagnosis of lung cancer one year prior to testing. Patients had to have at least three claims prior to, and 90 days of follow-up after, their test. Patients were stratified into three groups by pre- and post-test treatment: 1) patients treated with an EGFR tyrosine kinase inhibitor (TKI) as a first-line treatment after the test, with no other chemotherapy, ICI immunotherapy (IO), or targeted therapy before the test; 2) patients with other first-line treatments prior to the test and then EGFR TKI immediately following the test; and 3) patients treated with ICI or chemotherapy after the test and before EGFR TKI or patients not treated after the test. Real-world time to next treatment (rwTTN) was defined as the index date to the treatment different than the index therapy. Progression free survival (PFS) time was defined as rwTTN or time to death, whichever came earlier. Patients who experienced adverse events (AEs) associated with chemotherapy or IO were reported as a percentage (p-value<0.001). Results: Among the 3 cohorts of patients (384 in each group who were matched on age with difference < 3, gender, and follow-up time with difference < 4 months) identified, a statistically significant difference in PFS was discovered between group 1 ( EGFR TKI as first-line treatment) and the other two groups based on the Cox proportional hazard model [hazard ratio=1.8, p-value<0.001, median survival time for group 1= 26 months (95% CI 23-29) vs. 17 months (95% CI 14-19)]. No difference existed in PFS between groups 2 and 3. The proportion of patients experiencing treatment-associated AEs was lowest in group 1 (13.5% vs 15.9% in group 2 vs 30.2% in group 3 for ICI-related AEs, 16.9% vs 23.2% vs 38.5% for chemo-related AEs, p-value<0.001). Conclusions: Performing genomic testing sooner, as early as first-line treatment, may improve the treatment response for patients with NSCLC.

Management of Grade 3B Follicular Lymphoma (FL) Outside Clinical Trials: A Multicentric Retrospective Analysis on Behalf of Fondazione Italiana Linfomi (FIL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2716-2716
Author(s):  
Barbara Botto ◽  
Federica Cavallo ◽  
Manuela Zanni ◽  
Antonella Anastasia ◽  
Chiara Rusconi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Follicular Lymphoma ◽  
Retrospective Analysis ◽  
Progression Free Survival ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Rituximab Maintenance ◽  
First Line Treatment

Abstract Introduction: Follicular lymphoma grade 3 is recognized as a distinct entity in the World Health Organization classification of lymphoma. It is further classified into grade 3a and 3b depending on percentage of centroblasts. There is no consensus about its clinical course because some studies indicate an indolent behavior but others describe a more aggressive. Large systematic studies are missing in particular for 3b follicular lymphoma which is often considered as a separate entity. Methods: We performed a retrospective multicentric study on a group of 3b FL patients diagnosed in nine Italian FIL centers between November 2002 and January 2015. Planned inclusion criteria at enrollment were first line Rituximab containing regimen treatment and diagnostic samples availability for central pathologic review. Aim of the study was to determine clinical response, OS and PFS. Tumor response was based on the International Working Group response criteria. Survival analysis was performed with Kaplan-Meier method. Results: We enrolled a total of 51 patients, 50 evaluable for response at the time of analysis; median age was 62 yrs (range 48-71), 29 (56%) in stage III-IV, 10 (20%) with B symptoms. First line treatment was R-CHOP in the majority of patients 47 (92%), R-Bendamustine and R-CVP in 2 (4%) respectively. Seven patients (14%) received Rituximab maintenance after first line, six (12%) underwent high dose chemotherapy and autologous stem cell transplant (ASCT) as consolidation therapy and 5 (10%) were treated with local radiotherapy on residual disease. We observed CR in 48 patients (96%), PR in 1 (2%), PD in 1(2%). Ten patients relapsed or progressed after first line treatment and four of them died, three for progressive disease and one due to senile dementia while in CR. No relapses were recorded in pts receiving Rituximab maintenance but the advantage was not statistically significant and the number of patients receiving maintenance was low. With a median follow up of 63 months from diagnosis (IQR 33-82), 3-yrs PFS and OS rates were 82% and 93% (fig 1 and 2) with the evidence of a plateau in both survival curves after 5 years observation. Central pathologic review is ongoing. Conclusion: With the limit of a retrospective analysis our study confirms the clinical benefit of a combined modality treatment with Rituximab plus antracycline-containing chemotherapy in patients with 3b FL. Our results compare favorably with those previously reported in studies without Rituximab, that failed to show a plateau with 3-yrs PFS ranging between 22% and 52%. This results need to be confirmed with a longer follow up and after the planned pathologic review. Figure 1. Progression-Free Survival. Median Follow-up 62 months (IQR 33-82). Figure 1. Progression-Free Survival. Median Follow-up 62 months (IQR 33-82). Figure 2. Overall Survival. Median Follow-up 63 months. Figure 2. Overall Survival. Median Follow-up 63 months. Disclosures No relevant conflicts of interest to declare.

Retrospective Analysis of 41 Consecutive Patients with Non Gastrointestinal (GI) Extranodal Marginal Zone B-Cell Lymphoma (EMZL): Correlation of Clinical Characteristics and Outcome with Disease Localization.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4785-4785
Author(s):  
Christina Kalpadakis ◽  
Marina P. Siakantaris ◽  
Marie-Christine Kyrtsonis ◽  
Theodoros P. Vassilakopoulos ◽  
Tatiana Tzenou ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Characteristics ◽  
Marginal Zone ◽  
Advanced Stage ◽  
Line Treatment ◽  
First Line ◽  
Extranodal Site ◽  
Stage Disease ◽  
First Line Treatment

Abstract Extranodal marginal zone B-cell lymphomas of mucosa associated lymphoid tissue (MALT) are indolent lymphomas with specific clinical and pathologic features. MALT lymphomas can arise from any extranodal site. Non-gastrointestinal (non-GI) MALT lymphomas are rarer (<1% of NHL) and have been described in various sites (salivary glands, orbit, lung, skin etc). We retrospectively studied 41 patients with an initial diagnosis of EMZL according to the REAL/WHO classification criteria and presenting with a clinically dominant non-GI site of localization in order to evaluate the clinical characteristics of patients and to correlate disease localization with clinical behaviour, treatment and patient outcome. The studied population included 20 men and 21 women with a median age of 50 years (23–87). The most commonly affected sites were skin (13,32%), salivary glands (11%), followed by lung (7%), orbit (5%), oral cavity non salivary (4%), upper airway (1%) and thyroid (1%). The majority of patients (69%) presented in stage I. Advanced stage disease was due to bone marrow (12%) or/and lymph node involvement (12%), while in 4 patients there was more than one extranodal site involved. Autoimmune disorders were noticed in 7 patients, while monoclonal gamopathy in 5 (12%). Two patients presented B-symptoms (both with BALT ). Patiens with extranodal skin lymphoma (SALT) received treatment with interferon-α (54%), Mabthera iv or intralesionally (31%) or resection alone with a 100% CR rate. With a median follow up of 42 months no disease related death was noticed. Among 11 patients with salivary gland EMZL 5 had stage IV disease at presentation (45%). First line treatment was chlorombucil +/− Mabthera with a 90% CR rate. With a median follow up of 80 months two relapses in another MALT site (stomach) and one disease related death due to disease transformation were noticed. Patients with BALT lymphomas presented some specific clinical characteristics: There was a long time interval between onset of symptoms and diagnosis, B-symptoms were presented in 2 of 7 patients while most of them had symptoms from the respiratory system (cough, dyspnea, expectoration). 3 patients had advanced stage disease. First line treatment was chlorambucil +/− Mabthera +/− surgical excision with response rates of 70%. With a median follow up of 51 months two disease related death were noticed (one due to disease transformation). 4 of 5 patients with orbital MALT lymphoma received chlorambucil while one patient received radiotherapy alone. With a median follow up of 52 months one relapse to another extranodal site was noticed and no disease related death. In conclusion our data confirms the indolent behaviour of MALT lymphomas with a 5- and 10-year overall survival 82±8% and 65±13% respectively. The 5-year overall survival was 90% or more for each non-lung presentation vs 70% for BALT NHL. The optimal management of MALT lymphomas with regard to surgery, chemotherapy, immunotherapy and radiation therapy alone or in combination as well as abstention from therapy is not well defined. Additionally MALT lymphomas of various anatomic sites seem to present a clinical heterogeneity that may reflect heterogeneity at a molecular level.

Long Term Follow-up of the GELF86 French and Belgian Trials: Complete Remission after First Line Treatment with Conventional Chemotherapy in Newly Diagnosed Follicular Lymphoma Patients Correlates with Prolonged Overall Survival Compared with Partial Remission

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2590-2590 ◽  
Author(s):  
E. Bachy ◽  
P. Brice ◽  
M. Fournier ◽  
H. Tilly ◽  
C. Haioun ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Follicular Lymphoma ◽  
Tumor Burden ◽  
Line Treatment ◽  
Newly Diagnosed ◽  
First Line ◽  
Long Term Follow Up ◽  
First Line Treatment

Abstract Purpose . Frontline treatment for newly diagnosed follicular lymphoma (FL) patients, ranging from watch and wait policy to high-dose therapy, still remains debated, even in the rituximab-based combination therapy era. Few studies have addressed the question whether complete remission (CR) translates into better survival compared to partial remission (PR). The aim of this study was to assess the potential correlation between response quality to first line treatment and overall survival in light of a long-term follow-up. Patients and methods. Data from 536 FL patients, 435 enrolled in the French and Belgian GELF86 trials and 101 additional patients treated with the same chemotherapy regimen (CHVP-IFN or CHVP regimen after the accrual stopping date with prospectively collected data), were analysed in the study. Data from the GELF86 trials have been previously reported: 193 patients had low tumor burden (LTB) (Brice et al., JCO, 1997) and 242 and the aforementioned 101 additional patients had high tumor burden (HTB) at diagnosis (Solal-Céligny et al., NEJM 1993). All patients with at least one criteria for HTB were treated as frontline therapy with an anthracycline based CHVP regimen: cyclophosphamide, doxorubicin, teniposide, and prednisone monthly for 6 months and then every 2 months for 1 more year. Patients were randomly assigned to the CHVP arm (n=153) or the CHVP-IFN arm (n=190) when they also received α-interferon three times weekly for 18 months. Patients with LTB FL were randomly assigned to one of the three arms: arm 1, no initial treatment (n=66); arm 2, prednimustine for 5 days per month for 18 months (n=64); or arm 3, IFN three times per week for 15 months (n=63). Results. Median follow-up was 14.3 years and median overall survival (OS) was 9.8 years for the whole cohort. As expected, the Follicular Lymphoma International Prognostic Index (FLIPI) was a strong prognostic factor as well as bone marrow involvement, erythrocyte sedimentation rate (ESR), and B symptoms in univariate analysis or the FLIPI, lymphocytes count, ESR and male sex in multivariate analysis, respectively. Furthermore, treated patients who achieved a CR (n=170, 40%) had a significant longer OS than those only reaching a PR (n=162, 38%) throughout treatment (10-year OS was 64% (95% CI, 57–71%) for CR patients and 46% (95% CI, 38–54%) for PR patients, logrank p=0.0002). In a subgroup analysis by tumour burden, CR remained highly predictive of a better outcome for HTB patients (logrank p=0.001) but not for LTB patients. No difference was observed between patients who went into early complete remission (≤ 6 months) versus late complete remission (&gt; 6 months). Finally, when only HTB patients receiving CHVP-IFN were compared with those receiving the same treatment in the FL2000 trial (Salles et al., Blood, in press), Cox analysis adjusted for the FLIPI indicated a better outcome for FL2000 patients (HR=0.66, 95% CI 0.44–0.99, p=0.047). Conclusion. These data provide a long follow-up of these patients’ cohorts, and indicate strong evidence that better response to first line treatment translates into a favorable outcome for patients with newly diagnosed FL, especially for HTB patients.

Updated overall survival results of WJTOG 3405, a randomized phase III trial comparing gefitinib (G) with cisplatin plus docetaxel (CD) as the first-line treatment for patients with non-small cell lung cancer harboring mutations of the epidermal growth factor receptor (EGFR).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 7521-7521 ◽  
Author(s):  
Tetsuya Mitsudomi ◽  
Satoshi Morita ◽  
Yasushi Yatabe ◽  
Shunichi Negoro ◽  
Isamu Okamoto ◽  
...  
Keyword(s):  
Overall Survival ◽  
Phase Iii ◽  
Line Treatment ◽  
First Line ◽  
Significant Difference ◽  
The Impact ◽  
Egfr Tki ◽  
First Line Treatment ◽  
Platinum Doublet

7521 Background: WJTOG3405 met its primary endpoint of progression free survival (PFS) (9.2 months (mo.) for G vs. 6.3 mo. for CD, hazard ratio (HR) 0.489, 95% confidence interval (CI): 0.336-0.710). (Mitsudomi et al., Lancet Oncol., 2010). However, the impact on overall survival (OS) was not clear then because of relatively short follow-up period. Methods: Overall survival (OS) was re-evaluated using updated data (data cutoff, 31 July, 2011, median follow-up, 34 months) for 172 patients. Results: Eighty-two events had occurred (48%). Median survival time (MST) for G arm was 36 mo. (95% CI: 26.3 -) which was not significantly different from 39 mo. (95% CI: 31.2 -) for CD arm (HR 1.185, 95% CI 0.767-1.829). Multivariate analysis using Cox proportional hazards model revealed that none of covariates (treatment arm, smoking status, sex, age, postoperative recurrence or IIIB/IV, and mutation type) significantly affected OS. In the G arm, MST of patients with exon 19 deletion (36 mo.) was comparable to that of patients with L858R (35 mo.). In the CD arm, 78 patients (91%) received EGFR-TKI as the 2nd or later line treatment, whereas in the G arm, 52 patients (61%) received platinum doublet. Accordingly, 130 patients received both platinum doublet and EGFR-tyrosine kinase inhibitor (TKI) and 34 patients received EGFR-TKI without platinum doublet in their whole courses of therapy. MST for the former and the latter group were 36 months (95% CI: 31.2-45.7) and 45 months (95% CI: 25.6-), without significant difference. Conclusions: This update OS analysis revealed that G for advanced NSCLC with EGFR mutation offers distinct survival benefit of 3 years. There was no difference in OS whether the first-line treatment was G or CD, in accordance with the precedent studies. The reason why PFS difference was not translated into OS difference is probably due to high cross over rate to EGFR-TKI. However, it was noteworthy that 40% of patients in the G arm could be managed without platinum doublet and yet had similar outcome.

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