Myeloma in Martinique; Characteristics and Overall Survival

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5772-5772
Author(s):  
Anne Lok ◽  
jean-Come Meniane ◽  
Clarisse Joachim ◽  
Jacqueline Baudin ◽  
Jonathan Macni ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Data ◽  
Median Overall Survival ◽  
Genetic Profile ◽  
French Caribbean ◽  
First Line ◽  
Prognostic Features ◽  
Disease Characteristics ◽  
Caucasian Patients

Abstract Introduction African Americans (AA) are twice as likely to be diagnosed with multiple myeloma (MM) as Caucasian Americans (CA). Differences in overall survival have also been shown between those two populations with no consistent explanation with regard to social status or genetic profile given by gene expression profiling. In Martinique, where most of the population has African or French Caribbean ethnic origin with similar increased incidence in MM, we lack data about disease characteristics and survival as compared to French Caucasian patients. Material and methods The aim of this single center retrospective study was to evaluate characteristics, progression free and overall survival of this population. We analyzed 54 MM elderly patients consecutively treated in Fort de France Hematology department from March 2007 to March 2012. All patients received first line treatment with melphalan 0.2 mg/kg/d, prednisone 2 mg/kg/d and thalidomide 400 mg/d every 6 weeks according to French IFM guidelines. Disease characteristics and survival data were analyzed and compared to French Caucasian elderly MM patients included in first line IFM published trials. Results Population had a median age of 80 years (66 to 93). Concerning prognostic markers, International Scoring System (ISS) was of 3 (high) in 52% of patients and cytogenetic analysis showed rearrangements with translocation 14q32 in 22% with 7% of t(4;14). When considering deletion 13q, it was found in 41% and deletion 17p in 6%. With a median follow up of 35 months, survival features showed median overall survival (OS) of 48.6 months and progression free survival (PFS) of 28.9 months. Discussion Compared to French Caucasian patients, our series showed that Martinique’s population was older and presented more aggressive disease based on ISS. Moreover, almost half patients presented with MDRD clearance lower than 60ml/min which conferred higher B2m and worse prognosis. We also confirmed results recently published by Weiss and all who described lower rate of IgH translocation in African American population with MM. Despite higher median age and ISS, median overall survival of our population was unexpectedly similar to French published studies with IFM 99 06 trial showing median OS and PFS in MPT arm of 51.6 and 27.5 months respectively. In IFM 01/01 trial where patients were aged more than 75 with lower doses of melphalan and thalidomide, survival data showed median OS of 44 months and median PFS of 24.1 months. In meta analysis published by European Myeloma Network, median OS was even lower with 39.3 months. Our data tend to show that French Caribbean patients with first line MM treated in Martinique appear to have similar overall survival as compared to French Caucasian patients despite higher median age and more adverse prognostic features which has not been reported so far. We plan to confirm those data with new analysis with longer median follow up and extensive clinical and biological disease characteristics evaluation. Disclosures Moreau: celgene: Consultancy.

scholarly journals Treatment patterns and outcomes of patients with advanced malignant pleural mesothelioma in a community practice setting

2021 ◽  
Author(s):  
David M Waterhouse ◽  
Esmond D Nwokeji ◽  
Marley Boyd ◽  
John R Penrod ◽  
Janet L Espirito ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
Median Overall Survival ◽  
Treatment Patterns ◽  
Pleural Mesothelioma ◽  
Community Practice ◽  
Community Centers ◽  
First Line ◽  
Third Line

Aim: To assess real-world treatment patterns and outcomes among patients with advanced malignant pleural mesothelioma. Patients & methods: Retrospective database analysis. Results: In all, 469 patients received first-line systemic anticancer therapy (SACT) at community centers. Median follow-up from diagnosis was 11.6 months. Pemetrexed + platinum was the most common first-line SACT; similar proportions of patients received cisplatin or carboplatin with pemetrexed. Only a small proportion of patients received second- and third-line therapies. Median overall survival for first-line SACT was 12.0 months (95% CI: 10.7–14.2). Results were similar with pemetrexed + cisplatin and pemetrexed + carboplatin. Median overall survival with second-line SACT was 6.4 months (95% CI: 5.1–7.6). Conclusion: There is a need for more effective SACTs for advanced malignant pleural mesothelioma.

Treatment patterns following first-line pertuzumab + trastuzumab in patients with HER2+ metastatic breast cancer in the United States.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18746-e18746
Author(s):  
Sandhya Mehta ◽  
Melissa Pavilack ◽  
Jipan Xie ◽  
Raluca Ionescu-Ittu ◽  
Xiaoyu Nie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Treatment Duration ◽  
Median Overall Survival ◽  
Metastatic Breast ◽  
First Line ◽  
Line Of Therapy

e18746 Background: Limited real-world data exists on the treatment of HER2+ metastatic breast cancer (mBC) following pertuzumab (P)+trastuzumab (T) based regimens in first-line (1L) setting. In the EMILIA trial, T-DM1 had higher median progression-free survival (mPFS) (9.6 months vs. 6.4 months) and median overall survival (mOS) (30.9 months vs. 25.1 months) than lapatinib plus capecitabine in patients previously treated with trastuzumab and a taxane. Real-world treatment effectiveness data following 1L P+T could complement clinical trial data to help inform understanding of unmet needs of HER2+ mBC patients requiring second-line (2L) treatment. Methods: IQVIA Oncology EMR (US) database was analyzed to identify adult patients with confirmed HER2+ mBC who were treated with a 1L P+T based regimen between Jan 2015-Sep 2019. An anti-HER2-based regimen might include hormonal therapy and/or chemotherapy. Eligible patients who had ≥60 days of follow-up since 1L P+T regimen initiation were included in outcomes assessment. Treatment discontinuation was defined as a treatment gap of at least 365 days, initiation of a new line of therapy, or death. Treatment failure was defined as the initiation of a new line of therapy or death. A new line of therapy was defined as the use of another anti-HER2 agent, switching to a different class of chemotherapy, or re-initiation of the same regimen after a gap of at least 365 days. Median duration of anti-HER2 regimen, median time to treatment failure (mTTF) and median overall survival (mOS) were estimated using Kaplan-Meier analysis. Results: A total of 710 patients were treated with a 1L P+T based regimen (median age: 57 years; 47% HR+, 26% HR- and 27% unknown HR status; 80% received a taxane). Median follow-up was 20.3 months. Median treatment duration for 1L P+T regimens was 15.3 months. A total of 302 patients (43%) discontinued 1L P+T treatment during the study, of which 222 patients received 2L therapy with a median follow-up of 9.6 months post 2L initiation. Among patients receiving 2L treatment, 214 (96%) received anti-HER2-based regimens. T-DM1 based regimens were most common (n = 159; 72%), followed by trastuzumab-based regimens (n = 29; 13%), lapatinib-based regimens (n = 13; 6%) and neratinib (n = 13; 6%). Overall, median 2L treatment duration was 5.9 months, mTTF was 8.6 months, and mOS was 25.4 months. For patients receiving T-DM1 as 2L therapy, median duration of T-DM1 treatment was 5.7 months, mTTF was 7.9 months, and mOS was 24.4 months. Conclusions: T-DM1 was the most common 2L treatment following 1L P+T based regimen for HER2+ mBC. Median TTF and mOS for T-DM1 in this study were numerically shorter than mPFS and mOS reported in the EMILIA trial, possibly due to the inclusion of a broader patient population beyond those studied in a clinical trial in the current study. There remains an unmet need of a more effective treatment for HER2+ mBC after 1L treatment.

Survival Disparities Between African-American and Caucasian Patients with Multiple Myeloma Are Blunted in the Era of Novel Therapeutics and Autologous Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1395-1395 ◽  
Author(s):  
Nina Shah ◽  
Donna M Weber ◽  
Michael Wang ◽  
Sheeba Thomas ◽  
Jatin Shah ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
African American ◽  
Stem Cell ◽  
Median Overall Survival ◽  
Stage I ◽  
Single Center ◽  
Novel Therapeutics ◽  
Caucasian Patients

Abstract Abstract 1395 Poster Board I-417 Background: Multiple myeloma accounts for approximately 10% of hematologic malignancies diagnosed annually in the U.S. It is well documented that the African-American population is disproportionately affected by multiple myeloma in incidence and mortality. Survival data from the SEER database from 2001-2005 demonstrated higher mortality in African-American patients compared to Caucasian patients. However, more recent retrospective reviews in the era of autologous stem cell transplant (ASCT) did not support this finding. Thus the persistence of racial survival disparities in the era of ASCT and novel therapeutics is an evolving question. Methods: We performed a retrospective review of 170 African-American multiple myeloma patients and 170 age and gender-matched Caucasian patients initially seen at the M.D. Anderson Cancer Center from 1/1/2002 to 12/31/2008. Results: Three hundred forty previously untreated patients were analyzed. Median age at diagnosis was 57 years for both groups. For evaluable patients, the International Staging System at diagnosis was determined. The percentage of stage I, II and III patients in the African-American group was 53%, 28% and 19% respectively. The percentage of stage I, II and III patients in the Caucasian group was 40%, 30% and 29% respectively. These staging data were not significantly different between racial groups. In both groups, 89% of patients received a novel therapeutic (thalidomide, lenalidomide or bortezomib) during their treatment course. We found a statistically significant difference in the percentage of African-American and Caucasian patients who received high dose chemotherapy and ASCT (65% and 76%, respectively, p=0.04). There was no difference observed in the number of second transplants performed in the two groups (19 in both groups). Response to therapy is detailed in Table 1. There was no difference in overall response to any therapy of evaluable patients between the two groups. With a median follow-up time of 35 months, the median overall survival from diagnosis has not been reached in either group. Kaplan-Meir analysis shows that there is no difference in overall survival between black and white patients (p =0.1) Conclusions: In this single-center, retrospective study of multiple myeloma patients treated predominately with novel agents, with or without ASCT, no survival difference was observed between African-American and Caucasian patients. To our knowledge, this is the largest number of African-American myeloma patients analyzed for survival in a single-center study. Recognizing the potential disparities in healthcare access, this may not represent outcomes for all African-American patients with myeloma. Since median overall survival has not been reached in this data, it is possible that survival differences will become apparent in the future, and further follow-up is needed. However, this review suggests that in the era of novel therapeutics and ASCT resulting in improved overall response rates, survival in African-American patients may be equivalent to Caucasian patients. Further efforts are needed to enroll African-American patients on clinical trials to validate this observation prospectively. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Incidence and frequency of cancer cachexia during chemotherapy for advanced pancreatic ductal adenocarcinoma

2020 ◽  
Vol 28 (11) ◽  
pp. 5271-5279 ◽  
Author(s):  
Shuichi Mitsunaga ◽  
Eiji Kasamatsu ◽  
Koji Machii
Keyword(s):  
Overall Survival ◽  
Weight Loss ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Cancer Cachexia ◽  
Ductal Adenocarcinoma ◽  
Cancer Therapies ◽  
First Line ◽  
Timing Of Onset ◽  
Line Chemotherapy

Abstract Purpose Cachexia influences the patient’s physical wellbeing and quality of life, and the patient’s ability to tolerate their cancer therapies, especially cytotoxic chemotherapy. The purpose of this study was to investigate the frequency and timing of onset of cancer cachexia during chemotherapy and its association with prognosis and toxicity in patients with pancreatic ductal adenocarcinoma (PDAC). Methods We performed a retrospective study in patients who underwent first-line chemotherapy after diagnosis of advanced PDAC between 6 June 2008 and 31 March 2017. Base cachexia (weight loss up to 6 months before starting first-line chemotherapy) and follow-up cachexia (after starting first-line chemotherapy) were defined as weight loss > 2% with a body mass index (BMI) < 20 kg/m2 or weight loss > 5%. Results A total of 150 patients were registered. The median age and BMI were 65 years and 21.7 kg/m2, respectively. Base cachexia occurred in 50% of patients. Follow-up cachexia occurred in 32% within 12 weeks of starting first-line chemotherapy, reaching 64% at 1 year. Overall survival was not significantly different between patients with and without follow-up cachexia, regardless of whether cancer cachexia occurred within 12, 24, or 48 weeks of starting first-line treatment. Appetite loss, fatigue, nausea, and diarrhea were more frequent in patients with follow-up cachexia than in those without follow-up cachexia. Conclusion Follow-up cachexia had an early onset, but was not a prognostic factor for overall survival in patients with PDAC. Some adverse events tended to be more frequent in patients with follow-up cachexia than in those without follow-up cachexia.

scholarly journals Minimal Residual Disease Eradication with Venetoclax in Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 12-14
Author(s):  
Alexander Coltoff ◽  
Joseph G. Jurcic ◽  
Peter Campbell ◽  
Daniel J. Lee ◽  
Mark L Heaney ◽  
...  
Keyword(s):  
Overall Survival ◽  
Board Of Directors ◽  
Research Funding ◽  
Median Overall Survival ◽  
Residual Disease ◽  
Institutional Research ◽  
Negative Group ◽  
Advisory Committees ◽  
Research Grants

Introduction The combination of the BCL-2 inhibitor venetoclax with an HMA (HMA/Ven) has improved outcomes in previously untreated patients with AML not eligible for intensive induction therapy. In a phase Ib study, 67% of patients achieved a complete remission (CR) or CR with incomplete recovery of blood counts (CRi) with a median overall survival (OS) of 17.5 months (DiNardo CD et al. Blood 2019; 133(1):7-17). HMA/Ven has also demonstrated efficacy in a heavily pretreated population with relapsed or refractory (R/R) AML, the majority of whom had prior HMA exposure (DiNardo CD et al. Am J Hematol 2018; 93(3):401-7). Measurable residual disease (MRD) is recognized as an independent prognostic indicator important for risk stratification and treatment planning (Schuurhuis GJ et al. Blood 2018; 131(12):1275-91). To date, however, there have been few reports on the effect of HMA/Ven on MRD. Methods This is a retrospective case series of patients with AML at a single-center tertiary-care institution. Patients ≥ 18 years of age who were treated with HMA/Ven between January 2017 and June 2020, either in the upfront or salvage setting, for AML were included. Outcomes included CR/CRi rate, MRD response, relapse free survival (RFS), and OS. MRD was assessed via multicolor flow cytometry with a sensitivity of 10-3 (0.1%). Results Nineteen patients were identified, 12 (63%) of whom were female. The median age at the time of HMA/Ven initiation was 71 years (range, 21 - 87 years). Ten (53%) patients had de novo AML and 9 had secondary or therapy-related AML. By 2017 ELN criteria, 3 (16%) patients had favorable-risk, 9 (47%) had intermediate-risk, and 7 (37%) had adverse-risk AML. Nine (47%) patients had R/R AML; 5 received HMA/Ven as first salvage therapy, and 4 as 2nd or greater salvage. Three (16%) patients had prior HMA exposure. No patient had prior venetoclax exposure. Median follow-up was 9.1 months (range, 1-21.1 months). Ten (53%) patients received azacitidine and 9 (47%) were given decitabine. Venetoclax doses ranged from 50 to 400 mg daily, depending on participation in a clinical trial and concomitant medications. Eight patients achieved a CR and 7 patients achieved a CRi for a combined CR/CRi rate of 79%. The CR/CRi rate was 90% (9/10) in the upfront setting, and 66% (6/9) in the salvage setting. The median time and number of cycles to best clinical response was 2.3 months (range, 0.9-3.9 months) and 2 (range, 1-3 cycles), respectively. Eleven (73%) of the 15 responders achieved MRD clearance after a median of 2 cycles (range, 1-3 cycles) (Table 1). Two of 4 (50%) MRD-positive patients relapsed, while 4 (36%) of 11 MRD-negative patients relapsed (Figure 1). Relapse occurred at a median of 2.0 months (range, 1.3-2.7 months) in the MRD positive group and 11.0 months (range, 2.8-14 months) in the MRD negative group. One patient died of infectious complications while MRD negative. Three patients, all of whom were treated for R/R disease, proceeded to an allogeneic stem cell transplant (HSCT). Two were MRD negative at the time of HSCT and all remained in remission. At the time of data cutoff, 7 (64%) of 11 MRD-negative patients were alive, and all 4 MRD-positive patients were alive. Causes of death in the MRD-negative group included disease relapse (3 patients) and infection (1 patient). Median overall survival in the entire cohort (range, 32 days-NR) was not reached. Conclusions HMA/Ven was highly effective as both upfront and salvage therapy. Surprisingly, the salvage CR/CRi rate in this series was 66%, allowing half of the responders to proceed to HSCT. The majority (73%) of responders achieved MRD negativity. While MRD status influenced RFS, 36% of MRD-negative patients relapsed. Additionally, the same percentage of MRD-negative patients died during follow-up, versus none of the patients with MRD-positivity. This indicates the need for more sensitive methods to assess MRD and for novel therapeutic strategies to eliminate MRD, thereby improving long-term outcomes. Larger prospective studies are needed to define the role of MRD assessment with venetoclax-containing regimens. Disclosures Jurcic: AbbVie:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Celgene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;Syros Pharmaceuticals:Research Funding;PTC Therapeutics:Research Funding;Arog Pharmaceuticals:Research Funding;Kura Oncology:Research Funding;Forma Therapeutics:Research Funding;Astellas:Research Funding;Genentech:Research Funding;Novartis:Consultancy, Membership on an entity's Board of Directors or advisory committees;Daiichi-Sankyo:Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding;BMS:Consultancy, Research Funding.Campbell:AstraZeneca:Consultancy.Lee:Genentech:Research Funding;Sumitomo Dainippon Pharma Oncology, Inc.:Research Funding;AbbVie:Research Funding;Novartis:Research Funding;Bayer:Research Funding;Celgene:Consultancy;Forty Seven:Research Funding.Heaney:Blueprint Medicines Corporation:Research Funding;BMS:Research Funding;CTI Biopharma:Consultancy, Research Funding;Deciphera:Research Funding;Incyte:Research Funding;Novartis:Consultancy, Research Funding;Sierra Oncology:Research Funding;AbbVie:Consultancy;Partner Therapeutics:Consultancy.Lamanna:Janssen:Consultancy, Membership on an entity's Board of Directors or advisory committees;Octapharma:Research Funding;Juno:Other: Institutional research grants, Research Funding;Gilead:Consultancy, Membership on an entity's Board of Directors or advisory committees;Astra Zeneca:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Pharmacyclics:Consultancy, Membership on an entity's Board of Directors or advisory committees;Genentech:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Bei-Gene:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Abbvie:Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Institutional research grants, Research Funding;Oncternal, Verastem, TG Therapeutics:Other: Institutional research grants, Research Funding;MingSight:Other: Institutional research grants, Research Funding;Loxo:Research Funding;Celgene:Consultancy, Membership on an entity's Board of Directors or advisory committees;Columbia University Medical Center:Current Employment.

Three-year follow-up of ATTRACTION-3: A phase III study of nivolumab (Nivo) in patients with advanced esophageal squamous cell carcinoma (ESCC) that is refractory or intolerant to previous chemotherapy.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 204-204
Author(s):  
Keisho Chin ◽  
Ken Kato ◽  
Byoung Chul Cho ◽  
Masanobu Takahashi ◽  
Morihito Okada ◽  
...  
Keyword(s):  
Overall Survival ◽  
Subgroup Analysis ◽  
Survival Data ◽  
Special Interest ◽  
Safety Data ◽  
Phase Iii ◽  
Taxane Chemotherapy ◽  
Favorable Safety ◽  
Safety Signals

204 Background: Previous results from the ATTRACTION-3 phase 3 trial demonstrated a significant improvement in overall survival and a favorable safety profile compared with taxane chemotherapy (CT) in previously-treated ESCC patients. To our knowledge, no long-term efficacy and safety data of this immune checkpoint inhibitor has been reported in ESCC. Herein, we report the three-year survival data of Nivo in ESCC. Methods: In ATTRACTION-3, 419 patients with unresectable advanced or recurrent ESCC refractory or intolerant to 1 prior fluoropyrimidine/platinum-based CT were randomized in a 1:1 ratio to receive Nivo (N = 210) or the investigator’s choice of CT (paclitaxel or docetaxel) (N = 209) until disease progression or unacceptable toxicity. The primary endpoint was overall survival (OS). A subgroup analysis of OS according to the best overall response (BOR) was performed. The onset of treatment-related adverse events of special interest over time in the Nivo arm was also evaluated. Results: As of data cut-off on 25 May 2020, 3 years after the last patient was enrolled, the median OS (mOS) was 10.91 months with Nivo versus 8.51 months with CT [hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.64-0.97]. The OS rates of patients with Nivo and CT were 20.2 % and 13.5 % at 24 months, and 15.3% and 8.7% at 36 months, respectively. In the subgroup analysis of OS by BOR, mOS in CR/PR patients were 19.91 and 15.41 months (HR 0.84, 95%CI 0.46-1.54) and that in SD patients were 17.38 and 9.36 months (HR 0.45, 95%CI 0.26-0.78) in the Nivo and CT arm, respectively. Furthermore, mOS in PD patients were 10.91 and 6.18 months (HR 0.56, 95%CI 0.33-0.95) in the Nivo and CT arm, respectively. No new safety signals were detected during the three-year follow-up. Time to onset of the event of special interest was within the range of events previously observed in other indications. Conclusions: At three-year follow up, Nivo continued to show improved OS over CT in pretreated patients with advanced ESCC patients. Nivo showed a longer mOS than CT regardless of BOR. During the three-year follow-up, no new safety signals were observed. Clinical trial information: NCT02569242.

Larynx preservation after initial non-cisplatin containing combination chemotherapy plus radiotherapy, as opposed to surgical intervention with or without radiotherapy in previously untreated advanced head and neck cancer: final analysis after 12 years follow-up

1993 ◽  
Vol 107 (3) ◽  
pp. 211-216 ◽  
Author(s):  
L. A. Price ◽  
H. J. Shaw ◽  
Bridget T. Hill
Keyword(s):  
Overall Survival ◽  
Combination Chemotherapy ◽  
Median Overall Survival ◽  
Postoperative Radiotherapy ◽  
Local Therapy ◽  
Final Analysis ◽  
Entire Group ◽  
Larynx Preservation

After a median follow-up of 12 years, median overall survival of 73 patients with advanced squamous cell carcinoma of the larynx was 65 months. The 61 per cent of patients responding to two courses of initial schedule A combination chemotherapy, not including cisplatin, and the 81 per cent of patients achieving a final complete remission after definitive local therapy, had median overall survival figures of 95 and 97 months respectively. Overall survival and relapse-free survival in 51 patients treated with radiotherapy only with larynx preservation, were not significantly different from the 21 patients who completed their surgery with pre- or postoperative radiotherapy: median overall figures were 71 versus 65 months. These data add weight to our proposal that use of initial combination chemotherapy followed by radiotherapy may eliminate the need for radical surgery, so preserving the larynx in patients with advanced disease, and provides evidence of some long-term benefit with 32 per cent of this entire group surviving 12 years.

Frontline Therapy for Older Patients (pts) with Acute Myeloid Leukemia (AML): Clofarabine Plus Low-Dose Cytarabine Induction Followed by Prolonged Consolidation with Clofarabine Plus Low-Dose Cytarabine Alternating with Decitabine

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 336-336 ◽  
Author(s):  
Stefan Faderl ◽  
Farhad Ravandi ◽  
Guillermo Garcia-Manero ◽  
Xuelin Huang ◽  
Elias Jabbour ◽  
...  
Keyword(s):  
Overall Survival ◽  
Research Funding ◽  
Median Overall Survival ◽  
Low Dose ◽  
Response Rates ◽  
Newly Diagnosed ◽  
Secondary Aml ◽  
Prolonged Consolidation ◽  
Low Dose Cytarabine

Abstract Abstract 336 Standard therapy (e.g. “3+7”) of newly diagnosed older pts (≥ 60 yrs) with AML is characterized by low response rates, short response durations, and substantial toxicities. New approaches are therefore actively explored in clinical trials. Clofarabine is a second generation deoxyadenosine nucleoside analogue with activity in older pts with frontline AML and presence of unfavorable prognostic factors. In our experience, the combination of clofarabine with low-dose cytarabine achieved higher response rates at no increase of toxicity compared with clofarabine alone (Faderl S et al. Blood 2008). Based on the initial experience, we have designed a combination of lower-dose clofarabine plus low-dose cytarabine induction followed by a prolonged consolidation of these drugs alternating with decitabine to improve survival and maintain the high response rates from the earlier study. Pts were eligible if ≥ 60 yrs of age with newly diagnosed AML. Pts were excluded for ECOG PS > 2, creatinine > 1.5 mg/dL, cardiac ejection fraction < 40%, and prior therapy with clofarabine or decitabine. Induction therapy consisted of clofarabine 20mg/m2 i.v daily × 5 days plus cytarabine 20mg s.c. twice daily × 10 days. Responding pts could receive up to 17 courses of consolidation therapy of clofarabine plus cytarabine (over 3 and 7 days, respectively) during courses 1–2, 6–8, 12–14 alternating with decitabine 20mg/m2 i.v. daily for 5 days during courses 3–5, 9–11, and 15–17. All pts received antibiotic prophylaxis with levofloxacin, valacyclovir and itraconazole (or equivalent). Fifty-nine pts have been accrued with a median age of 70 yrs (range 60–81), of whom 17 pts (29%) were ≥ 75 yrs. Eleven pts (19%) had a PS of 2. Seven pts (12%) had a WBC of > 20,000/mcl at diagnosis. Thirty pts (51%) had abnormal cytogenetics. Molecular profile: FLT3/ITD 5 pts (9%), FLT3/D835 2 (4), NPM1 6 (13), Ras 2 (4). Thirteen pts (22%) had prior MDS (4 pts prior azacitidine; 2 pts prior lenalidomide) and 17 pts (29%) had secondary AML (Hx of prior chemo and/or XRT). Of 57 pts evaluable for response, 35 (61%) achieved CR and 4 (7%) CRp for an ORR of 68%. Six pts (11%) required more than one course to response. The ORR for pts with diploid vs abnormal cytogenetics was 79% vs 57%; for pts with prior MDS 46% vs 82% for pts with neither MDS nor secondary AML. All 7 pts with a FLT3 mutation responded. With a median follow up of 11.6 months (1.1-20.2+), 16 pts relapsed. Responses (CR) are ongoing in 19 pts. Median CR duration is 14.1 mos (1.8-16.4). Six pts (10%) died on study. Only one pt suffered an early death ≤ 28 days from induction (C1D26). Deaths were due to myelosuppression-associated infectious complications. Median overall survival for all 59 pts was 18.1 mos (0.8-20.2+). Median overall survival for responding patients has not been reached. The median number of consolidation cycles received by pts in CR/CRp was 4 (0-14). Fifteen of these pts have so far received at least 6 consolidation cycles. Most toxicities were ≤ grade 2 and included rash (64%), nausea (61%), transaminase elevations (58%), bilirubinemia (51%), diarrhea (32%), mucositis, creatinine evelations, and headache (12% each). Among toxicities > grade 2, transaminase elevations (14%) and bilirubinemia (5%) were most frequent. One pt (65 yr old female) experienced renal failure and pulmonary edema shortly following start of the induction. Myelosuppression and neutropenic fever were common, but prolonged myelosuppression in responders was rare. In summary, clofarabine plus low-dose cytarabine achieves high response rates with a manageable toxicity profile and low induction mortality in pts ≥ age 60 with previously untreated AML. Longer follow up and comparisons with conventional therapy will help establish whether or not this combination also has a survival advantage. Disclosures: Faderl: Genzyme: Honoraria, Research Funding; Eisai: Research Funding. Off Label Use: clofarabine and decitabine in AML. Kantarjian:Genzyme: Research Funding; Eisai: Research Funding.

Prognostic Impact of 3q21 and 3q26 Cytogenetic Abnormalities in Acute Myeloid Leukemia.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2594-2594
Author(s):  
Mario Annunziata ◽  
Piera Angelillo ◽  
Laura Vicari ◽  
Clelia Criscuolo ◽  
Felicetto Ferrara
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Platelet Count ◽  
Myeloid Leukemia ◽  
Median Overall Survival ◽  
Chromosome 3 ◽  
Prognostic Impact ◽  
Acute Myeloid

Abstract Abstract 2594 Background: Abnormalities affecting long arm of chromosome 3 are rare but recurrent in Acute Myeloid Leukemia (AML) and are detected in a variable percentage of AML patients according to different series. The 2008 World Health Organization classification recognizes AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) as a distinct subtype characterized by a poor prognosis. Allogeneic stem cell transplantation seems to improve outcome in eligible patients with these aberrations. Inappropriate expression of the ecotropic viral integration site 1 (EVI1) was demonstrated in virtually all patients with t(3;3)(q21;q26.2) and inv(3)(q21q26.2); as well as in a majority of patients with other 3q26 rearrangements. Other chromosome 3 abnormalities are rarely recognized in AML patients; clinical and prognostic relevance of these alterations is not yet defined. The aim of this study is to assess the prognostic impact of chromosome 3 abnormalities on disease characteristics and treatment outcome in AML. Patients and methods: A total of 580 consecutive adult patients were diagnosed with AML at our institution between February 2002 and July 2012. Conventional cytogenetic analysis performed on diagnostic bone marrow samples detected the presence of 3q abnormalities in 16 patients (2.7%). Two patients were lost to follow-up and were not evaluated for survival analysis. Molecular status of FLT3 and NPM1 was also performed and results are available for 10 patients. Median follow-up time for patients in this series was 47 months ( range 6–125). Results: There were 10 male and 6 female patients, the median age being 64.5 years (range 33–81), 10 patients had de novo AML while 6 evolved from a previously diagnosed myelodysplastic syndrome (MDS). Karyotype from MDS phase was available in 2 patients; both acquired 3q rearrangement at time of progression to AML. At time of diagnosis median haemoglobin value was 9.0 g/dL (range 4–11); median leucocyte count was 10.5 × 103̂/L (range 2.3 – 431). Median platelet count was 116 × 109̂/L (range 28 – 529), consistently with previous studies, which have shown that these patients present with higher platelet count at diagnosis when compared with no 3q rearranged ones. Regarding cytogenetic features 3 patients had t(3;3)(q21;q26), 3 patients had inv(3) (q21; q26), 3 patients showed a balanced rearrangement involving 3q26, while 6 patients harbored a del3q. One patient showed monosomy 3. Additional chromosomal changes were demonstrated in 5 patients, two of them had a complex karyotype (see Table 1), 3 had a monosomy 7. Thirteen patients out of 14 received intensive induction chemotherapy; complete remission (CR) was achieved in 5 patients (CR rate: 35.7%), the remaining 7 patients were resistant to induction as well as to salvage chemotherapy. Four patients underwent autologous stem cell transplantation. Median overall survival in this series is 5.5 months (range 0 – 20). At present only one patient is still alive and in CR, 20 months after diagnosis. Median disease free survival (DFS) for patients achieving a CR was 9 months (range 6–20). Median overall survival for patients resistant to first-line therapy was 3 months (range 0–6). Clinical features and treatment outcome of the patients are summarized in Table 1. Conclusions: The incidence of 3q abnormalities in our single institution series is 2.4%, in keeping with previous studies. Our findings confirm the association between these alterations and thrombocytosis at diagnosis, preceding MDS or multilineage dysplasia, presence in all FAB subtypes (except M3), association with additional chromosomal abnormalities as well as the poor response to conventional chemotherapy (CR rate 35.7%), and very short DFS in spite of obtaining CR. Disclosures: No relevant conflicts of interest to declare.

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