Outcome Of t(4;14) In Multiple Myeloma - Princess Margaret Cancer Centre Experience Over The Last 10 Years

Abstract Translocation (4;14) is identified by FISH cytogenetics in approximately 15% of myeloma patients (pts). Pts with this translocation have a poor outcome characterized by initial response to induction chemotherapy but followed by rapid relapse and resistance to alkylating agents. Recent studies have suggested that novel agents such as bortezomib may improve both event-free survival and overall survival (OS). We reviewed the outcome of 74 consecutive myeloma pts with t(4;14) managed at Princess Margaret Cancer Centre between October 2002 and July 2012. Our goal was to evaluate the impact of specific pts' characteristics on OS and to assess outcome according to treatments received. Clinical characteristics at time of diagnosis for the 74 myeloma pts with t(4;14) are presented in table 1. The average age was 57 years (range 31-82 years) and 58% were male. Pts received a median of 2 lines of therapy (range 1-6). Of the 69 pts requiring treatment, 46% of pts received one year of bortezomib as part of the Canadian t(4;14) clinical trial, 32% of pts were treated with novel agents including bortezomib (given for an average of 4 months) and lenalidomide, 22% of pts received conventional treatment such as dexamethasone alone, thalidomide and/or melphalan. 20 pts underwent autologous stem cell transplantation (ASCT) as part of their first line treatment; 16 were single ASCT, 4 were tandem ASCT. The overall response rate to induction chemotherapy was 70%, with 60% complete response/very good partial response and 10% partial response. The median OS was 5 years and 3 year OS was 66%. Presence of p53 significantly decreased the 3 year OS (71% vs 29% for absence and presence of p53, respectively, log-rank p value=0.0017). Median follow-up was 2.43 years (range: 0.24-11.81 years). There was no significant difference in OS based on the type of first line treatment received. The 3 year OS was 69% for pts enrolled in the t(4;14) clinical trial, 65% for pts who received novel agents and 53% for pts who received conventional treatment (log-rank p value=0.33). In a multivariable analysis looking at pts' initial characteristics, p53 deletion, LDH, bone lesions and age at diagnosis were found to be significant predictors of overall survival while ISS staging and immunoglobulin isotype were not found to be significant for overall survival. In conclusion, in our retrospective single institution study, the median OS for pts with t(4;14) was 5 years. Older age, addition of p53 deletion, high LDH and presence of bone disease predicted a worse OS. Although the lack of significant difference in OS based on the type of first line treatment received may be due to the limited number of pts in our study, there was a trend towards improvement in OS for pts that received a bortezomib containing regimen versus those who received conventional agents. While the median OS for pts with t(4;14) in our study has increased compared to historical controls, new therapeutic options are still needed to further improve the outcome in this subset of pts3. 3 Keats JJ et al. In multiple myeloma, t(4;14)(p16;q32) is an adverse prognostic factor irrespective of FGFR3 expression. Blood. 2003 Feb 15;101(4):1520-9.Table 1Clinical characteristics for the 74 myeloma pts with t(4;14)Clinical characteristicsAverageRange%Hemoglobin (g/L)10051-157Creatinine (μmol/L)13933-796Calcium (mmol/L)2.41.89-3.84B2-microglobulin (mg/L)4.51.58-20.25Albumin (g/L)3518-46ISS stage 145%ISS stage 236%ISS stage 319%Presence of bone lesions68%Mean % of nuclei positive for t(4;14)3%-71.5%25%Presence of del 13q/monosomy 13 by FISH77%Presence of del 17p by FISH10% Disclosures: Reece: Celgene: Honoraria, Research Funding; Jansen: Honoraria, Research Funding; Onyx: Honoraria; Novartis: Honoraria; BMS: Research Funding; Merk: Honoraria, Research Funding; Millennium: Research Funding.

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Prognostic importance of primary tumor resection and synchronous metastasis on overall survival in metastatic colorectal cancer: Data from the FIRE-3 (AIO KRK-0306) study.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.4070 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 4070-4070

Author(s):

Jobst C. von Einem ◽

Sebastian Stintzing ◽

Ludwig Fischer von Weikersthal ◽

Thomas Decker ◽

Alexander Kiani ◽

...

Keyword(s):

Overall Survival ◽

Primary Tumor ◽

Tumor Resection ◽

Primary Tumor Resection ◽

P Value ◽

Line Treatment ◽

First Line ◽

Significant Difference ◽

The Impact ◽

First Line Treatment

4070 Background: The FIRE-3 study (AIO KRK-0306) was designed as a randomized multicenter trial to compare the efficacy of FOLFIRI plus cetuximab (cet) to FOLFIRI plus bevacizumab (bev) as first-line treatment in KRAS WT mCRC patients. FOLFIRI plus cet as first-line treatment of KRAS WT mCRC patients resulted in comparable overall response rates (ORR) and progression free survival (PFS) when compared to FOLFIRI plus bev. Overall survival (OS) was significantly longer in the FOLFIRI plus cet arm. Methods: In the present analysis of the FIRE-3 trial we explored the impact of primary tumor resection on outcome in relation to anti-EGFR vs. anti-VEGF treatment. Furthermore, we investigated the prognostic value of synchronous versus metachronous metastases. Results: In patients with synchronous disease no significant difference in OS was detected when comparing resected (n=339) vs. non-resected (n=97) patients (p-value: 0.29, HR: 1.17, 95%-CI: 0.88 – 1.55). In the cetuximab arm, resection (n=167) showed no significant benefit in OS when compared to non-resection (n=52) (p-value: 0.51, HR: 1.15, 95%-CI: 0.77 – 1.71). Treated with bevacizumab, similar results were present, when comparing resection (n=172) vs. non-resection (n=45); (p-value: 0.29, HR: 1.25, 95%-CI: 0.83 – 1.9). A strong trend was seen when comparing OS in treatment arms cet. (n=219) vs. bev. (n=217)) for patients with synchronous disease; (p-value: 0.05, HR: 1,26, 95%-CI: 1.0 - 1.59). 436/592 pts suffered from synchronous, 153/592 from metachronous disease (in 3/592 pts the information was not given). Median OS in pts with synchronous disease was 24.5 months and 29.5 in pts with metachronous disease (p-value: 0.02, HR: 0.76, 95%-CI: 0.6 - 0.96). In pts treated in the cetuximab arm metachronous disease (n=77) was associated with a trend towards longer OS when compared to synchronous disease (n= 219) (p-value: 0.13, HR: 0.76, 95%-CI: 0.54 – 1.1). The same effect was present in the bevacizumab arm (p-value: 0.05, HR: 0.73, 95%-CI 0.53 – 1.0) when comparing pts with synchronous disease (n=217) vs. pts. with metachronous disease (n=76). Conclusions: In the FIRE-3 study, metachronous disease was associated with superior OS compared to synchronous disease. This finding was accentuated in the bevacizumab arm. The role of resection of the primary tumor had no impact on survival. Clinical trial information: NCT00433927 .

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Rituximab (Mabthera) Improves the Treatment Results of DHAP-VIM-DHAP and ASCT in Relapsed/Progressive Aggressive CD20+ NHL. A Prospective Randomized HOVON Trial.

Blood ◽

10.1182/blood.v108.11.328.328 ◽

2006 ◽

Vol 108 (11) ◽

pp. 328-328 ◽

Cited By ~ 1

Author(s):

Edo Vellenga ◽

Annelise Notenboom ◽

Mars van ‘t Veer ◽

Josée Zijlstra ◽

Willem E. Fibbe ◽

...

Keyword(s):

Disease Free Survival ◽

Response Duration ◽

Rank Test ◽

P Value ◽

Line Treatment ◽

First Line ◽

Post Transplantation ◽

Free Survival ◽

Significant Difference ◽

First Line Treatment

Abstract A total of 239 patients with relapsed/progressive aggressive CD20+ NHL after/during adriamycin containing regimens, were recruited to the randomized HOVON-44 trial comparing DHAP-VIM-DHAP followed by BEAM and autologous stem cell re-infusion (ASCT)(“DHAP-arm”) with DHAP-VIM-DHAP in conjunction with Rituximab (375 mg/m2) and ASCT (“R-DHAP arm”). Of the included patients, 202 were evaluable and randomized to the DHAP arm (n=101) or R-DHAP arm (n=101). Only patients with CR/PR after two courses of intensive chemotherapy were eligible for ASCT. Patients were well balanced for risk factors. In both arms the majority of patients had not been exposed to Rituximab during first line treatment. As of July 2006, median follow-up of all patients still alive is 24.5 months. After two courses of chemotherapy PR/CR was obtained in 49 % of the patients in the DHAP arm and 77% in the R-DHAP arm (p=<.01;intention to treat analysis). Post-transplantation PR/CR was obtained in 41% and 58% of the patients respectively (p=.40). A significant difference between both arms was observed for failure free survival (FFS), disease free survival (DFS) and overall survival (OS) in favor of the Rituximab arm (p<.05, table 1). The less pronounced difference in OS between both arms is most likely due to the fact that non-responding or relapsing patients in the DHAP arm received salvage treatment with a Rituximab containing regimen. Additionally, a subgroup analysis was performed according to type of response to first-line treatment:1) Response duration more than 3 months (n=138); 2) Progression or response duration less than 3 months (n=64). Within both subgroups, the hazard ratio’s for the endpoints were of equal magnitude (.40–.60), indicating that the beneficial effect of Rituximab existed in both subgroups. In conclusion these results demonstrate that the addition of Rituximab to second line of chemotherapy followed by ASCT results in a significant improved FFS, DFS, and OS in patients with relapsed/progressive aggressive CD20+ NHL. Table 1 FFS DFS OS *: 2 years estimate DHAP-arm* 21% 46% 48% R-DHAP arm* 52% 82% 62% Hazard ratio .40 .32 .61 p-value log rank test <0.001 0.003 0.03

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Major Improvement of Invasive Aspergillosis Outcome Is Not Enough to Improve Overall Survival In Allogeneic Hematopoietic Stem Cell Transplant Recipients: Results From a Single-Center Retrospective Analysis

Blood ◽

10.1182/blood.v116.21.1244.1244 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1244-1244

Author(s):

Géraldine Salmeron ◽

Raphaël Porcher ◽

Anne Bergeron ◽

Marie Robin ◽

Regis Peffault de Latour ◽

...

Keyword(s):

Overall Survival ◽

Board Of Directors ◽

Cumulative Incidence ◽

Research Funding ◽

Line Treatment ◽

First Line ◽

Advisory Committees ◽

Hematopoietic Stem ◽

Risk Of Death ◽

First Line Treatment

Abstract Abstract 1244 Background. Voriconazole (V) treatment has been shown to improve the 12 week (W) survival rate of hematological patients (pts) with invasive aspergillosis (IA), including recipients of allogeneic hematopoietic stem cell transplants (HSCT). We investigated whether this early survival advantage could translate into a significant increase in overall survival. Methods. We retrospectively reviewed all consecutive pts who received a transplant between Sept. 1997 and Dec. 2008 at Saint-Louis Hospital and were diagnosed as having IA. The temporal origin of the study was the date of IA diagnosis for each patient. Factors associated with survival were analyzed using Cox proportional hazard models. Separate models were estimated for survival up to 12 W and for survival between 12 W and 24 months (M) in pts surviving longer than 12 W. The deaths of pts with and without IA were analyzed with a competing risk framework. Cumulative incidence curves were compared using Gray's tests. Results. Our study examined 89 IA pts. The median follow-up was 70 M (range, 11–130 M). Two pts did not receive any antifungal treatment and were excluded from subsequent analyses. Of the 87 pts, 42 received first-line V and 45 primarily received a lipid formulation of amphotericin B (n=25), amphotericin B deoxycholate (n=10), caspofungin (n=8) or itraconazole (n=2). The primary characteristics of pts with IA and their causes of death, separated by V as first-line treatment, are shown in the table below. The median survival was 2.6 M, and the overall survival at 24 M was 19% (95% CI 12–30 M) (see figure). Overall, the survival rates of the two groups were significantly different (P= 0.010). However, the differences in survival were quite dramatic prior to 10 M, whereas both survival curves became very close after one year. At 18 M, the numbers of surviving pts were almost identical in the two groups [19% (95% CI: 11–34%) in pts who did not receive V as first-line treatment vs. 21% (95% CI 11–38%) in pts who did]. Pts who did not receive V as a first-line treatment displayed a higher probability of dying from IA than those who did (P=0.004), whereas opposite results were found for mortality in pts without IA (P=0.006). The 24-M cumulative incidence of death from IA was 47% (95% CI 31–61%) in the no V group and 19% (95% CI 9–33%) in the group treated with V. The 24-M cumulative incidence of death in pts without IA was 4% (95% CI 7–14%) in the no V group and 27% (95% CI 14–42%) in pts treated with V. The probability of death from another cause, with IA, was similar in both groups (29% vs. 36% at 24 M; P=0.46). After adjusting for donor type, conditioning regimen, progressive GVHD at diagnosis of IA and cumulated steroid dose (mg/kg) in the W preceding IA diagnosis, administration of V as first-line treatment was found to decrease the risk of death during the first 12 W by approximately 70% [HR=0.31 (95% CI 0.16–0.60); P=0.0005]. Conversely, analysis of mortality between 12 W and 24 M failed to identify any significant predictor of risk of death; however, only 24 pts died during this period. Conclusions. The finding that first-line treatment with V, which is associated with a tremendous improvement in IA outcome, does not translate into an increase in overall survival (even in the context of early diagnosis) is striking. Diagnosis of IA following HSCT, whatever the outcome, appears to be a strong marker for poor long-term prognosis. Disclosures: Bergeron: Pfizer: Speakers Bureau, none; Merck: Speakers Bureau, none; Schering: Speakers Bureau, none. Sulahian:Pfizer: Research Funding, non; Merck: Research Funding, none. Ribaud:Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau, none; Schering: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau, none; Gilead: Speakers Bureau, none.

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Comparison of quality-adjusted survival in patients with advanced renal cell carcinoma receiving first-line treatment with temsirolimus (TEMSR) or interferon-α (IFN) or the combination of IFN+TEMSR

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.5049 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 5049-5049 ◽

Cited By ~ 7

Author(s):

S. Parasuraman ◽

G. Hudes ◽

D. Levy ◽

A. Strahs ◽

L. Moore ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Overall Survival ◽

Cell Carcinoma ◽

Renal Cell ◽

Health State ◽

Line Treatment ◽

First Line ◽

Significant Difference ◽

Grade 3 ◽

First Line Treatment

5049 Background: In a phase 3, randomized, 3-arm study of TEMSR or IFN or the combination of TEMSR + IFN in the first-line treatment of patients with advanced renal cell carcinoma (RCC) and poor-prognostic features, TEMSR improved overall survival (p=0.0069) and progression-free survival (p=0.0001) vs. IFN (Hudes et al. J Clin Oncol. 2006;24:LBA4). Quality-adjusted survival was a pre-defined endpoint and is reported. Methods: Quality-adjusted time without symptoms and toxicity (QTWiST) was estimated by partitioning overall survival into 3 distinct health states: time with serious toxicity, time with progression, and time without symptoms and toxicity (TWiST). Survival was value-weighted when patients completed quality of life questionnaires (EQ-5D) at weeks 12 and 32, when a grade 3 or 4 adverse event (AE) was reported, upon relapse or progression, or upon withdrawal from the study. Treatment group comparisons used restricted means analyses estimated from censored survival data. Restricted means were computed for duration of each health state by truncating data at median follow-up (17.9 months). Variance and covariance were estimated using bootstrap methods. Results: All 626 randomized patients in the study were included in computation of health state durations. EQ-5D questionnaires were obtained from 260/300 (87%) upon progression and 230/570 (40%) after a grade 3/4 AE. Patients receiving TEMSR alone had 38% greater TWiST than those receiving IFN alone (TEMSR=6.5 months vs. IFN=4.7 months, p=0.00048). There was no significant difference in TWiST between the combination arm and IFN alone (IFN+TEMSR=5.4 months vs. IFN=4.7 months, p=0.1288). Patients receiving TEMSR alone had 23% greater Q-TWiST than those receiving IFN alone (TEMSR=7.0 months vs. IFN=5.7 months; p=0.0015). There was no significant difference in Q-TWiST for the combination arm compared with IFN alone (IFN+TEMSR=6.1 months vs. IFN=5.7 months, p=0.3469). Conclusions: Patients with advanced RCC receiving TEMSR alone had significantly greater quality-adjusted survival than those receiving IFN alone. No significant financial relationships to disclose.

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Impact Of Rituximab Maintenance Schedule On Prognosis In First Line Treatment Of Follicular Lymphoma. Retrospective Analysis From Czech Lymphoma Group (CLG) Database

Blood ◽

10.1182/blood.v122.21.4387.4387 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4387-4387

Author(s):

Andrea Janikova ◽

Zbynek Bortlicek ◽

Vit Campr ◽

Leos Kren ◽

David Belada ◽

...

Keyword(s):

Overall Survival ◽

Follicular Lymphoma ◽

Retrospective Analysis ◽

Research Funding ◽

Statistical Significance ◽

Induction Treatment ◽

Line Treatment ◽

First Line ◽

Rituximab Maintenance ◽

First Line Treatment

Abstract Introduction Results of randomized studies showed benefit of maintenance therapy with monoclonal anti-CD20 antibody (rituximab) in terms of time to progression (PFS) and overall survival (OS) in follicular lymphoma (FL). General recommendation, based on large clinical trial, is to give 2 years of rituximab maintenance á 375mg/m2every 2 months (12 doses) in first line setting. On the other hand, there are various rituximab maintenance schedules; however, the clear comparison of clinical efficacy is missing. Our retrospective analysis compared two different schedule of rituximab maintenance in first-line treatment of FL used in university centers participating on CLG registry. Methods Data were recruited from 1702 FL patients registered in the prospectively maintained multicentric database (Czech Lymphoma Group; CLG). For the analysis, patients with stage II-IV of new diagnosed FL (grade 1-3a) responding (complete or partial remission) to 6-8 cycles first-line RCHOP (rituximab, cyclophosphamide, doxorubicine, vincristine and prednisone) followed with rituximab maintenance (RM) were included. Completed planned maintenance was inclusion criterion. Patients with previous watch and wait or additional first line therapy (radiotherapy, other chemotherapy, transplant therapy) were excluded. Results Totally, 168 evaluable FL patients with median age 57ys (range 28-82) including 70 (41.7%) men treated with RCHOP + RM were found in CLG database. 52/168 patients received totaly 8 doses of rituximab maintenance every 3 months for 2 years (RM8 arm), whereas 47/168 patients were treated with totaly 12 doses (RM12 arm) of rituximab maintenance every 2 months for 2 years. All patients in both subgroups completed planned RM therapy. There was no difference in distribution of age, gender, FLIPI, grade, B-symptoms, bone marrow involvement, performance status, LDH and beta2microglobuline level between both arms. Induction treatment in terms of administered cycles CHOP (6xCHOP in 41/52 and 35/45 pts., for RM8 and RM12 arm) and rituximab doses (8xR in 48/52 and 41/45 pts., for RM8 and RM12 arm) was similar between arms (ns). There were 4/52 (7.7%) and 5/47 (10.6%) relapses in subgroups RM8 and RM12, with no statistical significance. Median PFS was 3.8 (2.1-5.8) years vs. 3.9 (2.4-7.8) years in RM8 and RM12 arms (not significant), and median OS 3.91 (2.2-6.94) years vs. 3.1 (2.48-8.6) years also with no statistical significance. Conclusion Our results show, that rituximab maintenance given every 2 or every 3 months for two years in first line treatment brings similar benefit to the FL patients in terms of remission duration and overall survival. Despite the fact, that presented data are retrospective observation, this is the first report comparing two different rituximab maintenance regimens in FL. Further prospective study and longer follow up are needed to confirm our preliminary data. This work was supported by grant NT/12193-5 and MHCZ-DRO (FNBr 65269705) Disclosures: Mayer: Roche: Consultancy, Research Funding; Glaxo: Consultancy, Research Funding. Trneny:Roche: Honoraria, Research Funding.

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Racial Variations in Disease Characteristics, Presentations, Treatments, and Outcomes in Chronic Lymphocytic Leukemia (CLL)

Blood ◽

10.1182/blood.v124.21.1989.1989 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1989-1989

Author(s):

Chadi Nabhan ◽

Kari G. Rabe ◽

Susan L Slager ◽

Sara J Achenbach ◽

Susan Schwager ◽

...

Keyword(s):

Overall Survival ◽

Research Funding ◽

Line Treatment ◽

First Line ◽

Prospective Data ◽

Purine Analogue ◽

Disease Characteristics ◽

Hispanic White ◽

First Line Treatment ◽

White Patients

Abstract Introduction: Our current understanding of CLL biology and optimal therapies is based on clinical trials that have largely enrolled White patient populations. Whether these findings are applicable to Hispanic or non-White patients is unknown but critical to evaluate given the growing numbers of minority patients in the U.S. While retrospective studies have suggested inferior outcomes in non-White patients, prospective data on these disparities are lacking. Patients and Methods: We utilized the Mayo Clinic CLL database to better understand variations in disease characteristics, molecular differences, and treatment selections between non-Hispanic White patients and those not in this category (referred to hereafter as “other race”). After excluding 49 patients with missing diagnosis date and another 490 patients with missing race and/or ethnicity, the remaining 4104 cases within the registry were included in the analysis. Comparisons by race were made using Chi-square or Wilcoxon rank sum tests for qualitative or quantitative variables, respectively. Overall survival (OS) was calculated from diagnosis until death or last known alive date; time to first treatment (TTFT) was calculated from diagnosis until treatment date or date last known to be untreated. OS and TTFT were displayed via Kaplan-Meier plots, and differences in OS and TTFT by race were calculated using log-rank statistics. Individuals who were enrolled in early intervention trials (n=61) were excluded from analyses involving treatment. Results: In total, 4104 CLL patients were identified: 4011 (97.7%) non-Hispanic Whites and 93 (2.3%) other races. Median age at CLL diagnosis was younger for other race patients (59 vs. 63 years; p=0.002), while gender and stage distributions were comparable between both groups. Serum β-2-microglobulin and absolute lymphocyte counts at diagnosis were similar but more other race patients had elevated LDH (29.5% vs. 16.1%; p=0.02). Cytogenetic data by FISH were available for 1884 non-Hispanic Whites and 46 other race patients; poor-risk cytogenetics (17p and/or 11q deletions) were present in 23.9% of other race and 13.5% of non-Hispanic White patients, respectively (p=0.04). No statistically significant differences were observed for CD38, ZAP-70, or IGHV by race TTFT was similar for both non-Hispanic Whites and other race patients (4.6 vs. 5.5 years, respectively; p=0.12). First-line treatment selection was similar for both groups (Table). . With a median follow-up of 12.1 years, median overall survival was 9.3 years for other race and 12.2 years in non-Hispanic White patients (P=0.15; Figure). Conclusions: This prospective data supports the notion that CLL might be biologically different between non-Hispanic White and other race patients with less favorable FISH present in the latter group. Despite the observation that TTFT and type of first therapy are similar between both groups, the trend towards shorter OS in other race patients argues that other factors might contribute to outcome differences, such as disease biology, access to care, co-morbidities, and socioeconomic considerations. Further studies with larger cohorts are warranted. Table: First-line treatment selection among treated individual by racial First-line Treatment Non-Hispanic Whites(n=1875) Other race(n=41) Chemoimmunotherapy Purine analogue-based Alkylator-based 675 (36.0) 495 (26.4) 180 (9.6) 15 (35.6) 9 (22.0) 6 (14.6) Purine analogue -monotherapy 157 (8.4) 4 (9.8) Alkylator monotherapy 610 (32.5) 9 (22.0) PA+Alkylator 41 (2.2) 1 (2.4) Antibody alone 190 (10.1) 6 (14.6) Other 202 (10.8) 6 (14.6) Figure: Overall survival in CLL cases stratified by race Figure:. Overall survival in CLL cases stratified by race Disclosures Nabhan: Genentech: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; Janssen: Honoraria, Speakers Bureau. Kay:Celgene: Research Funding. Shanafelt:Genentech: Research Funding; GlaxoSmithKline: Research Funding; Celegene: Research Funding; Cephalon: Research Funding; Pharmacyclics/Jannsen: Research Funding; Hospira: Research Funding; Polyphenon E Int'l: Research Funding.

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Impact of New Therapies On the Survival of Elderly (≥75 Years of Age) Previously Untreated Patients with Multiple Myeloma in a Community Hospital

Blood ◽

10.1182/blood.v120.21.4251.4251 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4251-4251

Author(s):

Romany Johnpulle ◽

Simran Sindhu ◽

Lynn Nichols ◽

Lynda Dimitroff ◽

Mehul Patel ◽

...

Keyword(s):

Overall Survival ◽

Elderly Patients ◽

Novel Agents ◽

Response To Treatment ◽

Line Treatment ◽

First Line ◽

Median Serum ◽

One Year ◽

First Line Treatment ◽

Novel Agent

Abstract Abstract 4251 Multiple myeloma (MM) is an incurable clonal plasma cell malignancy. At least 50% of all MM patients are older than 70 years of age and 20% are older than 80 years of age (Siegel R, Naishadham D, Jemal A. CA Cancer J Clin. 2012 Jan-Feb;62(1):10–29). The approach to treatment of patients with MM depends on a multitude of factors including age, underlying comorbidities, and disease characteristics. Elderly patients are under-represented in clinical trials. The purpose of our study was to assess the overall outcomes and impact of novel agents in the treatment of newly diagnosed elderly (≥75 years of age) patients with MM in a community setting. We conducted a retrospective review of the records of MM patients seen at Rochester General Hospital, Rochester, NY, who were 75 years of age or older at the time of diagnosis of MM. The study period was from January 2001 to August 2012. Sixty-six patients met the study criteria. Patients with smoldering MM were excluded. Demographic information, comorbid conditions, disease characteristics, laboratory data, first line treatment given, response to treatment, and disease- and treatment-related complications were collected from medical records. Data were analyzed using SPSS software version 14. Univariate analysis was performed and the mean, median, and standard deviation were calculated. A statistically significant difference between variables was denoted by a p value < 0.05. Response to treatment was calculated using Bladé Criteria. Overall survival was estimated by using Kaplan-Meier curves. Grade III and IV toxicity was determined according to Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI) version 4.0. Sixty-six patients (median age 81 years, range 75–95 years) with symptomatic MM were studied. Sixty-two percent were males. Twenty-seven percent had underlying diabetes mellitus, 29% had experienced a prior stroke or MI, and 68% had hypertension. Charlson Co-morbidity Index (CCI) was high (3–4) in 46% and very high (≥5) in 31%. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was ≥3 in 27% of patients. Sixty-five percent of patients had IgG subtype, while 28% had IgA subtype. There was a predominance of kappa light chains over lambda (55% versus 42%). Twenty percent, 34%, and 40% of patients had International Staging System (ISS) stages 1, 2, and 3, respectively, while in 6% ISS could not be determined. The median hemoglobin level was 10.5 g/dL (range 6.1–14.8 g/dL), the median serum creatinine level was 1.3 mg/dL (range 0.1–8.0 mg/dL), the median serum albumin level was 3.2 g/dL (range 1.4–4.8 g/dL), and the median serum calcium level was 8.7 mg/dL (range 8.0–17.3 g/dL). As first line treatment 75% received standard therapy, while 25% received novel agents. The most commonly used standard therapies were cyclophosphamide + steroid (36%), melphalan + steroid (25%), and steroid alone (8%). First line therapy included bortezomib in 12%, thalidomide in 10%, and lenalidomide in 3% of patients. Median duration of first line treatment was 26 weeks (range 3–103 weeks). The median overall survival was 72 weeks (range 10–406 weeks). In those who received a novel agent as first line therapy the median overall survival was 127 weeks (range 38–318 weeks). Overall response rate (≥ partial response) was 55% in patients treated with a novel agent versus 23.6% in patients treated with standard therapy. There was no significant correlation between grade III/IV toxicity and the use of a novel agent (p=0.68). When including all non-transplant patients (> 65 years of age), there was a positive correlation between the use of a novel agent and overall survival at one year (Correlation coefficient, CC 0.281, p=0.01). The CC for elderly patients (≥ 75 years of age) was 0.175. The CC in 65–74 year-olds was 0.387. Percentage survival at one year was 59.6 % in patients ≥75 years of age versus 70.6% in those aged 65–74 years. In conclusion, our study shows that very elderly patients (≥75 years of age) with MM, who are considerably ill at baseline with a high or very high CCI and poor PS continue to experience shortened survival despite the use of new agents. However, notwithstanding this, the early use of novel agents has a positive impact on survival at one year, with improved response rates to new therapies, and without an increase in toxicity. Disclosures: Patel: Millennium Pharmaceuticals, Inc: Speakers Bureau; Eli Lilly and Company: Speakers Bureau.

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Impact Of Major Molecular Response On Overall Survival and Its Time Of Achievement On Complete Molecular Response Incidence In Chronic Myeloid Leukemia Patients Treated By Tyrosine Kinase Inhibitors In First Chronic Phase

Blood ◽

10.1182/blood.v122.21.2721.2721 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2721-2721

Author(s):

Mauricette Michallet ◽

Mohamad Sobh ◽

Helene Labussiere ◽

Lila Gilis ◽

Fiorenza Barraco ◽

...

Keyword(s):

Overall Survival ◽

Median Time ◽

Research Funding ◽

Kinase Inhibitors ◽

Molecular Response ◽

Line Treatment ◽

First Line ◽

Sokal Score ◽

Hasford Score ◽

First Line Treatment

Abstract Most patients with CML treated with Tyrosine Kinase Inhibitors (TKIs) achieve a major molecular response (MMR), that is, the absence of detectable Philadelphia chromosome. Even after this threshold is achieved, the disease burden continues to progressively decrease with continued treatment. Therefore, more sensitive polymerase chain reaction (PCR)–based molecular methods are required to detect and quantify levels of minimal residual disease leading to complete molecular response (CMR), especially at long time points after TKI initiation. Low levels of minimal residual disease, as measured by real-time quantitative PCR, have been shown to be an excellent surrogate marker for long-term prognosis. The objective of the present study is to describe the different clinical and therapeutic characteristics of chronic myeloid leukemia (CML) patients consecutively treated in first chronic phase (CP1) using tyrosine-kinase inhibitors (TKI) as first line treatment, followed at our centre between years 2001 and 2011, and at a second time to assess response to TKI with the incidence of major molecular response (MMR) and then its evolution to reach complete molecular response (CMR). Among 253 consecutive CML patients treated in CP1 at our centre, we analysed 183 (72%) who received TKI as first line treatment, 117 males and 66 females with a median age at diagnosis of 50 years (17-81)]. Among 135 patients evaluated for Sokal score, 41 (30%) were low, 63 (47%) were intermediate and 31 (23%) were high. According to hasford score (125 evaluated), 57 (46)% were low, 61 (49%) intermediate and 7 (5%) were high. First line treatment was imatinib for 161 (88%) patients, dasatinib for 14 (8%) patients and nilotinib for 8 (4%) patients. Overall, 167 (91%) patients obtained MMR [134 (80%) after first line treatment, 26 (16%) after second line treatment and 7 (4%) after third line treatment] within a median time of 13 months (range: 2-88); and 16 (9%) patients never reached MMR. Non-MMR patients, were as follow: 53% had high sokal score 33% intermediate and 14% low; 6% had high hasford score, 47% intermediate and 47% low; they received a median of 3 TKI-based treatment lines during a median follow-up of 37 months; 6 (37.5%) of them died after disease progression and 10 still under treatment. The median time to obtain MMR was correlated with sokal score: 9 months (range: 2-84) in patients with low score; 13 months (range: 3-78) in patients with intermediate score and 17 months (range: 3-63) in patients with high score, p=0.03, same according to hasford score with 11 months, 13 and 20 months respectively, p=0.05. Among MMR patients, 18 (11%) lost their MMR after a median time of 28 months (range: 3-65) while 57 (34%) achieved a CMR after a median time of 36 months (range: 0-73) from MMR. Interestingly, response enhancement from MMR to CMR was significantly impacted by the time to have a MMR, thus the 5 years incidence of CMR was 67% in patients who had MMR in ≤ 3 months, 56% in patients with MMR > 3 and ≤ 12 months, 28% in patients with MMR > 12 and ≤ 24 months, and 12% in patients with MMR > 24 months, p=0.01 (Figure 1). After a median follow-up of 62 months (range: 6-135), patients who were in MMR at 24 months had 5 years probability of overall survival of 99% compared to 64% for those who did not have it at that time nor later, p <0.001 (Figure 2).Figure 1CMR incidence according to time to obtain MMRFigure 1. CMR incidence according to time to obtain MMRFigure 2Overall survival for patients in MMR at 24 months vs. those never in MMRFigure 2. Overall survival for patients in MMR at 24 months vs. those never in MMR We showed that MMR is a very significant factor predicting patient overall survival independently of treatment line number and delay of its achievement. In addition, we demonstrated that patients with low Sokal and Hasford scores have significant faster time to achieve MMR and that CMR incidence was significantly related to shorter time to obtain MMR. Disclosures: Michallet: Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; MSD: Consultancy, Honoraria, Research Funding; Genzyme: Consultancy, Honoraria, Research Funding.

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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).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.7521 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 7521-7521 ◽

Cited By ~ 47

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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Real life data from Turkey regarding the impact of first-line sunitinib and pazopanib in metastatic renal cell cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e16075 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e16075-e16075 ◽

Cited By ~ 1

Author(s):

Ulas Isik ◽

Osman Kostek ◽

Gokcen Demiray ◽

Ahmet Dirican ◽

Melih Simsek ◽

...

Keyword(s):

Overall Survival ◽

Renal Cell ◽

The Other ◽

Line Treatment ◽

First Line ◽

Treatment Approaches ◽

Common Cancer ◽

Significant Difference ◽

The Impact ◽

First Line Treatment

e16075 Background: Although the distribution in the world varies widely, renal cell carcinoma (RCC) is the ninth most common cancer, especially in males. It’s the seventh most common cancer in Turkey. In this study, the progression-free survival (PFS) and overall survival (OS) of patients with metastatic RCC (mRCC) who were treated at 13 centers in our country were evaluated and the efficacy of first-line treatment approaches was compared. Methods: Data of mRCC patients admitted to 13 outpatient clinics in Turkey between 2008 and 2018 were reviewed retrospectively. Demographic characteristics, pre-treatment clinical evaluations, information about treatment approaches and survival outcomes of the patients were collected. All medical records were collected by a detailed review of the patients’ charts. The median and percentage values were frequently signified for defining of central trends. Kaplan-Meier method was applied for OS analyzes and log-rank test with Cox-regression models were applied for the evaluation of prognostic factors. Results: Data from files of 262 patients were reviewed. Twelve of these patients were excluded from the study because they could not receive treatment due to comorbidities and other reasons at metastatic stage of the disease. Of the patients, 100 (40%) were female and 150 (60%) were male. Median age was 60 (range 21-83). For the entire group, the median PFS (mPFS) was 27.6 months and the median overall survival (mOS) was 46.1 months. In terms of first-line treatment of metastatic disease, 41.3% of the patients received sunitinib, 48.8% of the patients received pazopanib, 15.8% of the patients received other treatments. PFS of the patients receiving sunitinib, pazopanib and the other treatments were 26.3 months, 34.2 months and 14.2 months, respectively. There was no statistically significant difference between PFS of the patients receiving sunitinib and pazopanib (p = 0.05). mOS was 54 months in sunitinib arm, 54.9 months in pazopanib arm and 23.3 months in the other treatment arm. There was no statistically significant difference between two treatment agents in terms of mOS (p = 0.43). Conclusions: Pazopanib was more commonly prescribed in Turkey. There were no statistically significant differences between mPFS and mOS of the patients who received sunitinib and pazopanib for the first-line treatment of mRCC. With increased use of immunotherapeutic agents for the first-line treatment of mRCC in our country, improvement in mOS could be expected.

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