Effectiveness of a Strategy to Proceed to Allogeneic Stem Cell Transplantation in All Elderly AML Patients Treated with Intensive Chemotherapy: Only Patients in Complete Remission After First Induction Show Long Term Survival.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3085-3085
Author(s):  
Peter A. Von Dem Borne ◽  
Constantijn J.M. Halkes ◽  
Erik W.A. Marijt ◽  
Sabina Kersting ◽  
J.H. Frederik Falkenburg ◽  
...  
Keyword(s):  
Overall Survival ◽  
Induction Chemotherapy ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Consolidation Chemotherapy ◽  
Early Relapse ◽  
Kaplan Meier ◽  
Elderly Aml ◽  
Treat Population

Abstract Abstract 3085 Introduction Acute myeloid leukemia (AML) in patients over 60 years has a poor prognosis with 2-year survival rates of less than 10%. Intensive chemotherapy improves interim survival but not long term cure rates compared to non-intensive care. Allogeneic stem cell transplantation (alloSCT) has the potential to cure elderly AML patients, but most reported studies refer to selected patient cohorts. We have developed a T cell-depleted reduced intensity conditioning (RIC) regimen and preplanned post alloSCT donor T-cell infusion, inducing only limited GVHD directly after alloSCT (von dem Borne et al. Curr Opin Oncol 2009) making it a suitable regimen for elderly patients. In 2006, we instituted a center policy to perform RIC alloSCT in every newly diagnosed AML and high grade MDS patient >60 years who qualified for induction therapy. We here report feasibility, toxicity, and outcomes of this strategy. Patients and methods From 2006 to 2011, 45 consecutive patients aged 60–79 years (median: 67) with newly diagnosed AML (n=43) or high-risk MDS (IPSS score >1.5) started induction chemotherapy (continuous infusional cytarabine combined with bolus anthracycline with or without etoposide). Patient not achieving complete remission (CR) after induction received a re-induction cycle with high-dose cytarabine with or without amsacrine. Patients in CR after induction or re-induction were to receive one cycle of consolidation chemotherapy, followed by RIC alloSCT in case of continuous CR. Results Six patients (13%) died during first induction. 19 patients (43%) achieved CR after first induction, of which 12 received a RIC alloSCT (27% of intention-to-treat population) after consolidation chemotherapy. Causes why CR patients did not receive alloSCT were good-risk AML (n=1), early relapse after consolidation chemotherapy (n=2), high age (patient had become over 80 years) (n=1), infectious complication (n=1) and patient choice (n=2). 20 patients (45%) failed to achieve a CR after induction chemotherapy. 16 of these patients received the planned re-induction therapy; 10 of these patients achieved a CR, 7 patients received a third chemotherapy course for consolidation, and 4 underwent RIC alloSCT. There were no long-term survivors in this group. 19 patients without CR after 1st induction died from progressive AML.15 AML deaths after 1st induction failure occurred in patients who were treated according to the institutional strategy (6 patients with progressive disease despite additional chemotherapy, 1 relapse prior to start of re-induction, 3 relapses early after consolidation, and 4 relapses after alloSCT). Relapses in patients not adhering to the pre-specified strategy occurred in patients opting to discontinue therapy while in CR (n=3), inability to find a donor (n=1), and complication preventing alloSCT (n=1). One transplanted patient died from GVHD. For the entire intent-to-treat population, the Kaplan-Meier estimate for overall survival at 1 and 2 years after start of treatment is 38% and 19%, respectively. For patients achieving CR after 1st induction and receiving alloSCT, Kaplan-Meier estimate overall survival at 2 years after start of treatment is 50%. The main reasons for dying when adhering to the protocol were early death (13%) and refractory/relapsing malignancy (47%). Only 2 patients (4%) died after 1st induction as a consequence of TRM. Non-TRM reasons for not adhering to the protocol with subsequent death due to AML were patient preference (n=4; 9%) and inability to identify a matched donor (n=1; 2%). Conclusions This single-center comprehensive cohort study shows that 38% of elderly AML patients that are deemed fit for induction chemotherapy can be brought to alloSCT in CR. At diagnosis, this strategy offers a chance of cure for about 20% of patients. Fifty percent of patients achieving CR after 1st induction and receiving alloSCT are alive 2 years after alloSCT. Since none of the patients who failed to achieve a CR after 1st induction survived long-term, the most important aspect to improve this strategy is to strive for higher primary CR rates, including the prevention of early deaths. Alternative strategies, such as combining alloSCT and consolidation chemotherapy into one coherent regimen may especially improve outcome by preventing early relapse and improving patient compliance. Post-induction TRM and lack of a donor were only minor obstacles to this potentially curative approach. Disclosures: No relevant conflicts of interest to declare.

Elderly AML Patients Treated with Intensive Chemotherapy- Developing A Prognostic Scoring System. A Study On 381 Patients From British Columbia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2561-2561
Author(s):  
Satish Krishnan ◽  
Huihua Li ◽  
Yasser R Abou Mourad ◽  
Michael J. Barnett ◽  
Raewyn Broady ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Induction Chemotherapy ◽  
Cox Regression ◽  
Risk Group ◽  
Performance Status ◽  
Risk Groups ◽  
Remission Induction ◽  
Intensive Chemotherapy ◽  
Consolidation Chemotherapy ◽  
Elderly Aml

Abstract Abstract 2561 Introduction. AML in patients above age 60 is associated with adverse outcomes compared to younger patients. This is due to the higher incidence of adverse risk cytogenetic changes, poor performance status and end organ function that precludes patients from receiving intensive chemotherapy. Large population based studies have reported 5yr survival rates of 5–8% even in patients receiving standard ‘3+7’ induction chemotherapy. Our study looks at the effect of disease and patient characteristics on outcomes in elderly AML patients who received remission induction chemotherapy in the hope of predicting which individuals would benefit most from this treatment. Patients and Methods. Retrospective data was collected from 381 patients > age 60 who underwent conventional cytarabine and daunorubicin (7+3) induction and consolidation chemotherapy after clinical evaluation suggesting they were fit for such treatment, from Jan 1990 to Sept 2009. The follow up duration ranged from 6m–19.5 years. The data collected were age, ECOG performance status,Haematopoetic stem cell transplant comorbidity Index (HCI) (Sorror et al Blood 2005;106:2912),WBC at presentation, bone marrow blast percentage, antecedent hematologic disease (AHD), Cytogenetic risk group by MRC(UK) criteria, remission status, date of relapse, mortality and overall survival (OS). Statistical analysis was performed to determine variables affecting OS using Cox regression analysis. Multivariate Cox regression coefficients were used to generate a nomogram to predict OS based on Akaike's information criterion. Results. The CR rates in the 3 MRC risk groups were 95%,75% and 40% respectively. The 8 week mortalities in the 3 risk groups 10%,8%and 29% respectively. The 3 month survival was 85%, 1year 50% and 5yr 16% for the patients as a whole. Multivariate analysis showed that age at diagnosis, WBC, cytogenetic risk group and AHD affect OS while sex, ECOG, HCI and BM blast count do not. Using the 4 variable significantly predicting OS a nomogram was developed. Its ability to predict OS of individual patients was evaluated using bootstrapping of a set of 200 resamples. To use the nomogram, draw a line straight upwards to the points axis to determine the number of points received for each of the 4 variables. The sum of these numbers is located on the Total Points axis, and a line is drawn downward to the survival axes to determine the likelihood of 1-, 3- or 5-year OS Discussion. AML in patients > age 60 is typically associated with a poor outcome after intensive chemotherapy. However, even among this high risk group results are heterogeneous. This is illustrated in our study where the CR rate and induction mortality varied substantially across cytogenetic risk groups. In addition to the cytogenetic risk group we found age, WBC at diagnosis and the present of AHD to have prognostic value in this elderly group. However, the HCI was not predictive of survival in these AML patients > age 60 receiving standard induction and consolidation chemotherapy. The prognostic patient factors identified in multivariate analysis are easily available in newly-diagnosed AML patients, usually before decisions regarding initial therapy must be made. If confirmed in a larger prospective study, the nomogram we have developed will help clinicians predict the expected survival following intensive chemotherapy, thus helping the patient to make an informed choice regarding risk vs benefit. Disclosures: Sutherland: Centocor Ortho Biotech research & Development: Research Funding.

scholarly journals Physical and Psychological Impairments As Practical Frailty Markers in Elderly AML Fit for Intensive Chemotherapy; Interim Data of a Prospective Cohort Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3831-3831
Author(s):  
GI June MIN ◽  
Byung Sik Cho ◽  
Sung-Soo Park ◽  
Silvia Park ◽  
Young-Woo Jeon ◽  
...  
Keyword(s):  
Cohort Study ◽  
Board Of Directors ◽  
Induction Chemotherapy ◽  
Prospective Cohort ◽  
Research Funding ◽  
Handgrip Strength ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Elderly Aml

Background The comprehensive geriatric assessment (CGA) typically refers to a multidimensional assessment designed to evaluate an older person's functional ability, physical health, cognition, psychological health, nutritional status, and social support. There is a significant heterogeneity in terms of their underlying health and resilience to the burden of disease and treatments in elderly AML (eAML). To date, a few have evaluated the predictive value of CGA among newly diagnosed eAML. The purpose of this study is to investigate the potential clinical value of CGA as a screening test for frailty in eAML. We designed a comprehensive CGA battery with measures which previously validated, standardized, and widely used. This study is a single-center prospective observational cohort study focused on discriminating between those older patients who are fit for intensive therapies and those who are vulnerable and may experience excess toxicity. Patients and method This prospective cohort study is to investigate the predictive values of each domain of CGA to discriminate vulnerable patients in eAML fit for intensive chemotherapy. Between November 2016 and July 2019, we enrolled newly diagnosed eAML patients aged ≥60 years considered fit for intensive chemotherapy, who had adequate performances and organ functions. All the enrolled patients were administered various questionnaires for an initial CGA and functional evaluation divided into 3 categories; (1) Social and Nutritional support (OARS and MNA), (2) Psychological (MMSE-KC, SGDS-K, PHQ-9, NCCN distress thermometer, MADRS, and KNU-DESC), and (3) Physical function (ECOG, KIADL, SPPB, Handgrip strength, and PTA by professional ENT evaluation). Results Seventy-seven patients were enrolled, in whom the median age of 64 years (range, 60-74), 58.4% were males, and 93.5% and 77.9% of patients had on ECOG score of 0~1 and HCT-CI score of 0~2, respectively. All enrolled patients were treated with intensive chemotherapy, and 62.3% achieved the first complete remission. Three patients experienced early death within 60 days (3.9%). During induction chemotherapy, the median recovery period for neutrophil and platelet counts was 26 (range, 24-29) and 30 (range, 27-33) days, respectively. The median hospitalization days for induction chemotherapy were 32 days (range, 21-104), and infection and GI complications (NCI-CTC-AE based any grade 79.2% and 67.5% respectively) were the most common complications primarily affecting tolerance to the initial chemotherapy. The grade III to IV infection, GI complications, hepatopathy, and acute kidney injury developed in 67.5%, 42.9%, 37.7%, and 16.9% of patients, respectively. Physical impairments were significantly associated with a higher incidence of infection (intact vs. any impairments; 46.4% vs. 79.6%, p=0.003), of which handgrip strength was most accurate tool to predict infection risk (p =0.032), and a trend of more GI complications (intact vs. any impairments; 28.6% vs. 51.0%, p=0.056), resulting in prolonged hospitalization (intact vs. any impairments; 32.2±1.7 days vs. 37.5±2.1 days, p=0.088) for the period of induction chemotherapy. Psychological impairment (intact vs. any impairments; 30.9±1.3 days vs. 38.2±2.1 days, p=0.005), particularly cognitive dysfunction measured by MMSE-KC (p=0.033), was also significantly associated with prolonged hospitalization. Conclusions This data demonstrates that a significant proportion of eAML fit for intensive chemotherapy based on performance status and comorbidity had social, nutritional, physical, psychological impairments by initial CGA assessments. These interim data focusing on early events suggest that impaired physical and/or psychological functions would be useful to identify eAML with intolerance to intensive chemotherapy. This ongoing exploratory prospective study will enroll more eAML patients (targets number=100) and further follow up currently enrolled patients, which will give us invaluable data to develop practical frailty marker and a new model for fitness for intensive chemotherapy. Disclosures Kim: Takeda: Research Funding; Novartis: Research Funding; BMS: Research Funding; Pfizer: Research Funding; Il-Yang co.: Research Funding. Lee:Achillion: Research Funding; Alexion: Consultancy, Honoraria, Research Funding. Kim:Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Hanmi: Consultancy, Honoraria; AGP: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; SL VaxiGen: Consultancy, Honoraria; Novartis: Consultancy; Amgen: Honoraria; Chugai: Honoraria; Yuhan: Honoraria; Sanofi-Genzyme: Honoraria, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Handok: Honoraria; Janssen: Honoraria; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees; Otsuka: Honoraria; BL & H: Research Funding.

scholarly journals Incidence of spinal disease and role of spinal radiotherapy in multiple myeloma

2018 ◽  
Vol 25 (6) ◽  
Author(s):  
A. M. Sharma ◽  
M. Sackett ◽  
D. Bueddefeld ◽  
P. Lambert ◽  
A. Dubey ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Systemic Therapy ◽  
Cox Regression ◽  
Cord Compression ◽  
Newly Diagnosed ◽  
Spinal Disease ◽  
Kaplan Meier ◽  
Long Term Survivors

Background Spinal disease (spd) in multiple myeloma (mm) can be a major source of morbidity in newly diagnosed patients and long-term survivors. We retrospectively assessed the incidence of spinal disease in patients newly diagnosed with myeloma, its effect on survival, and the possible effect of spinal radiation therapy (rt).Methods Patients diagnosed with mm between 2010 and 2014 were identified through the provincial cancer registry. Plain radiography, computed tomography, and magnetic resonance imaging were reviewed to detect and document the type of spd. Data related to rt and systemic therapy were collected. Kaplan–Meier and time-varying Cox regression models were used to describe overall survival.Results Of 306 identified patients with newly diagnosed mm, 51% had spd, including 17% with lytic disease, 68% with compression fractures, and 15% with spinal cord compression. Of the patients with spd, 61% received spinal rt. Of those patients, 84% received spinal rt within 3 months after their diagnosis. Median dose was 20 Gy. Most patients (89.2%) received chemotherapy, and 22.5% underwent autologous stem-cell transplantation. Only 6 of the patients treated with spinal rt received re-irradiation to the same site. Overall survival was similar for patients with and without spd. On multivariate analysis, spinal rt had no effect on survival.Conclusions In patients newly diagnosed with mm, spd is a common presentation. With current systemic therapy, the presence of spd had no adverse effect on overall survival. The effect of spinal rt on overall survival was nonsignificant.

Albumin Is a Prognostic Factor for Overall Survival in Newly Diagnosed Patients with Acute Myeloid Leukemia (AML)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4253-4253
Author(s):  
Awais M. Khan ◽  
Jeffrey E. Lancet ◽  
Mohamed A. Kharfan-Dabaja ◽  
Najla H Al Ali ◽  
Alan F. List ◽  
...  
Keyword(s):  
Overall Survival ◽  
Serum Albumin ◽  
Induction Chemotherapy ◽  
Serum Albumin Level ◽  
Cox Regression ◽  
Albumin Level ◽  
Normal Serum ◽  
Newly Diagnosed ◽  
Kaplan Meier ◽  
History Of

Abstract Abstract 4253 Background: Hypoalbuminemia (HA) is a strong predictor of poor clinical outcomes in many medical conditions. Low serum albumin is recognized as an adverse prognostic factor in patients with neoplastic diseases such as multiple myeloma, melanoma, and colon cancer. Severe hypoalbuminemia (<3.0 g/dl) at day +90 post allogeneic hematopoietic cell transplant (AHCT) was reported as an independent predictive variable for non-relapse mortality and overall survival (Kharfan-Dabaja, et al Biol Blood Marrow Transplant 2009; 15). A separate study conducted by our group showed that in patients with relapsed and refractory AML, serum albumin < 3.5 g/dl prior to salvage chemotherapy, correlated with lower complete remission (CR) rate and inferior overall survival (OS) (Komrokji, et al ASH 2009). We examined the prognostic value of serum albumin level prior to induction chemotherapy in patients with newly diagnosed AML. Methods: Data were collected retrospectively in a cohort of newly diagnosed AML patients who received induction chemotherapy (3+ 7 regimen). The primary objective of this study is to examine the relationship between serum albumin at baseline and probability for achieving complete remission (CR) or incomplete remission (CRi) and overall survival (OS). All analyses were conducted using SPSS version 19.0. The Kaplan–Meier method was used to estimate median overall survival; chi-square test was used for comparison of categorical variables and t-test for continuous variables. Log rank test was used to compare Kaplan–Meier survival estimates between two groups and Cox regression for multivariable analysis. Results: Between November 2004 and July 2007, 135 patients who received 3+7 induction chemotherapy at Moffitt Cancer Center were included in this analysis. Patient baseline characteristics were similar between patients with baseline serum albumin < 3.5 g/dl (HA) and those with serum albumin ≥ 3.5 g/dl (no HA) with respect to age, sex, FAB subtype, history of antecedent MDS, karyotype, and chemotherapy. Patients with HA, mean age was 60 years compared to 56.5 years in non HA group. The median OS for patients with HA was 221 days (95%CI 149.5–292.5) compared to 421 days (95%CI 236.7–605) with normal serum albumin (p<0.005). (Figure-1) The CR/CRi rate was 64%% for HA and 77.6% for those with normal albumin (p=0.09). In a multivariable Cox regression analysis including age ≥ 60 years, history of MDS, karyotype, and serum albumin level at baseline; only age, karyotype and serum albumin were independent predictors of OS [Hazard ratio 0.47 (95%CI 0.31–0.71) (p<0.005) for normal serum albumin group]. Conclusion: In this cohort of patients with newly diagnosed AML, we demonstrate that hypoalbuminemia < 3.5 g/dl is an independent covariate for overall survival with conventional chemotherapy management. Serum albumin is a surrogate marker of general health, comorbidities, and performance status. The prognostic value of low serum albumin should be validated in a prospective study. Disclosures: No relevant conflicts of interest to declare.

Albumin as a prognostic factor for overall survival in newly diagnosed patients with acute myeloid leukemia (AML).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6586-6586
Author(s):  
Awais M. Khan ◽  
Jeffrey E. Lancet ◽  
Mohamed A. Kharfan-Dabaja ◽  
Najla Al Ali ◽  
Alan F. List ◽  
...  
Keyword(s):  
Overall Survival ◽  
Serum Albumin ◽  
Induction Chemotherapy ◽  
Prognostic Value ◽  
Serum Albumin Level ◽  
Albumin Level ◽  
Normal Serum ◽  
Newly Diagnosed ◽  
Kaplan Meier ◽  
History Of

6586 Background: Hypoalbuminemia (HA) is an adverse prognostic factor in multiple neoplastic diseases. Severe hypoalbuminemia (<3.0 g/dl) at day +90 post allogeneic hematopoietic cell transplant (AHCT) was reported as an independent predictive variable for non-relapse mortality and overall survival (Kharfan-Dabaja, et al Biol Blood Marrow Transplant 2009; 15). We examined the prognostic value of serum albumin level prior to induction chemotherapy in patients with newly diagnosed AML. Methods: Data were collected retrospectively in newly diagnosed AML patients receiving induction chemotherapy (3+ 7 regimen). Primary objective was to examine the relationship between serum albumin at baseline and probability of achieving complete remission (CR) or incomplete remission (CRi) and overall survival (OS). The Kaplan–Meier method used to estimate median overall survival; chi-square test used for comparison of categorical variables and t-test for continuous variables. Log rank test used to compare Kaplan–Meier survival estimates between two groups. Results: Between November 2004 to July 2007, 135 patients who received 3+7 induction chemotherapy were included. Patient baseline characteristics were similar between patients with serum albumin < 3.5 g/dl (HA) and those with serum albumin ≥ 3.5 g/dl (no HA) with respect to age, sex, FAB subtype, history of antecedent MDS, karyotype, and chemotherapy . In patients with HA, mean age was 60 years compared to 56.5 years in non HA group. The median OS for patients with HA was 221 days (95%CI 149.5-292.5) compared to 421 days (95%CI 236.7-605) with normal serum albumin (p<0.005). (Figure-1) The CR/CRi rate was 64%% for HA and 77.6% for those with normal albumin (p=0.09). In a multivariable Cox regression analysis including age ≥ 60 years, history of MDS, karyotype, and serum albumin level at baseline; only age, karyotype and serum albumin were independent predictors of OS [Hazard ratio 0.47 (95%CI 0.31-0.71) (p<0.005) for normal serum albumin group]. Conclusions: In newly diagnosed AML, we demonstrate that hypoalbuminemia < 3.5 g/dl is an independent covariate for overall survival with conventional chemotherapy management. The prognostic value of low serum albumin should be validated in a prospective study.

A Randomized Open-Label Study To Evaluate The Efficacy Of Azacitidine For Post-Remission Therapy Of Acute Myeloid Leukemia In Elderly Patients (QOLESS AZA-AMLE)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3967-3967
Author(s):  
Esther Natalie Oliva ◽  
Stella Santarone ◽  
Pietro Leoni ◽  
Caterina Alati ◽  
Antonio Volpe ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Best Supportive Care ◽  
Intensive Chemotherapy ◽  
Consolidation Chemotherapy ◽  
Open Label ◽  
Elderly Aml ◽  
Acute Myeloid

Abstract Background The incidence of acute myeloid leukemia (AML) increases with age. In elderly AML patients, intensive chemotherapy has been associated with complete remission (CR) rates of approximately 45%, considerably lower than in younger patients; the duration of remission is shorter and the early treatment-related mortality is high, 30% to 50%, which partially explains a median survival of 7 to 12 months. Several studies have suggested that maintenance therapy may improve CR duration and long-term, disease-free survival (DFS). Grovdal et al (2010) treated 60 elderly patients with high-risk myelodysplastic syndrome (MDS) or AML with cytarabine-based induction therapy resulting in CR in 24 patients who continued on to 5-Azacitidine (5-Aza) maintenance therapy. The median duration of complete response was 13.5 months. The median OS for the 5-Azacitidine-treated group was 20 months. Aims The present phase III, prospective, randomized, open-label, multicenter trial is designed to assess the efficacy of post-remission treatment with 5-Aza versus best supportive care in a cohort of subjects of > 60 years of age with AML, and in CR after conventional induction (“3+7”) and consolidation chemotherapy. Primary objectives are to evaluate overall survival overall survival and DFS at 2 years; secondary objectives are to evaluate the number and length of hospitalizations in the 2 arms in the 2-year post-remission period. Methods Approximately 95 patients with the following criteria: newly diagnosed AML with > 30% myeloid marrow blasts, either “de novo” or evolving from a MDS not previously treated with chemotherapeutic agents; no contraindications for intensive chemotherapy and performance status<3 will be included. Thirty-eight patients will be randomized in the post-remission phase 1:1. Standard induction chemotherapy consists of two courses of 3 + 7 with Daunorubicin at a daily dosage of 40 mg/m2 for 3 days (days 1-3) in combination with 100 mg/m2 cytarabine per day as a continuous IV infusion for 7 days (days 1-7). Consolidation consists of cytarabine 800 mg/m2 3 hour infusion bid (days 1-3). Patients in CR are randomized 1:1 to receive best supportive care (BSC) or 5-Aza according to the following schema: 50 mg/sqm s.c. or i.v. for 7 days every 28 days and increase after 1st cycle, if well tolerated, to 75 mg/m2 s.c or i.v. for 7 days (5 + weekend off + 2) every 28 days for further 5 cycles, followed by 6 cycles every 56 days for 2 years post-remission. Results At the time of the present report 58 patients have been included in the study. Median age at diagnosis was 72, interquartile range (IQR) 65-75 years, M/F 34/24. During induction-consolidation chemotherapy, 16 patients were relapsed/refractory, 9 patients died, 3 patients were excluded for protocol violation, 3 refused to continue and 8 have not yet reached consolidation treatment. Nineteen patients have been randomized; characteristics of patients are shown in the table. Eighteen patients have reached at least a 4 week follow-up. Amongst these, 11 patients are still in CR at a median observation time of 25.4, IQR 12.9-47.4 weeks. Five patients in the BSC arm have experienced AML recurrence at 7, 8, 13, 21, 49 weeks, respectively, verus 2 patients in the 5-Aza arm at 42 and 47 weeks. DFS is longer in the 5-Aza arm (Figure). Grade 3-4 adverse events included neutropenia in 2 cases in the 5-Aza arm and in 1 case in the BSC arm. There were no hospitalizations related to the adverse events in either arm. Conclusions Preliminary results suggest that in elderly AML patients receiving standard induction-consolidation chemotherapy, 5-Aza post-CR is well-tolerated and may prolong survival. Disclosures: Oliva: Celgene: Consultancy. Off Label Use: Azacitidine is indicated for the treatment of adult patients who are not eligible for haematopoietic stem cell transplantation with: • intermediate-2 and high-risk myelodysplastic syndromes (MDS) according to the International Prognostic Scoring System (IPSS), • chronic myelomonocytic leukaemia (CMML) with 10-29 % marrow blasts without myeloproliferative disorder, • acute myeloid leukaemia (AML) with 20-30 % blasts and multi-lineage dysplasia, according to World Health Organisation (WHO) classification.

Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors.

1998 ◽  
Vol 16 (1) ◽  
pp. 210-221 ◽  
Author(s):  
W P Mason ◽  
A Grovas ◽  
S Halpern ◽  
I J Dunkel ◽  
J Garvin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Brain Tumors ◽  
Disease Progression ◽  
Induction Chemotherapy ◽  
Residual Disease ◽  
Significant Proportion ◽  
Intensive Chemotherapy ◽  
Newly Diagnosed ◽  
Consolidation Chemotherapy ◽  
Malignant Brain Tumors

PURPOSE To evaluate a strategy that avoids radiotherapy in children less than 6 years of age with newly diagnosed malignant brain tumors, by administering myeloablative consolidation chemotherapy with autologous bone marrow reconstitution (ABMR) after maximal surgical resection and conventional induction chemotherapy. PATIENTS AND METHODS Between March 1991 and April 1995, 62 children (median age, 30 months) with newly diagnosed malignant brain tumors were enrolled onto this trial. Children received conventional induction chemotherapy with vincristine, cisplatin, cyclophosphamide, and etoposide, repeated every 3 weeks for five cycles. Children without disease progression on induction chemotherapy were offered consolidation with myeloablative chemotherapy that incorporated carboplatin, thiotepa, and etoposide followed by ABMR. Irradiation was used only for residual tumor at consolidation or for progressive/recurrent disease. RESULTS Induction chemotherapy was well tolerated by most patients; however, progression was noted in 17 children (27%) and four (6%) died of treatment complications. Of 37 children who received consolidation chemotherapy with ABMR, 15 are free of disease progression (median post-ABMR without further treatment, >44 months). The remaining 22 all progressed within 15 months of ABMR; three of 37 (8%) died of treatment-related complications. The 3-year overall survival (OS) and event-free survival (EFS) rates from diagnosis for all children are 40% (95% confidence interval [CI], 28% to 52%) and 25% (95% CI, 13% to 37%), respectively. Radiotherapy was administered to 19 of 62 children: 17 for progressive disease (PD) and two for residual disease at the time of ABMR. CONCLUSION A significant proportion of children with malignant brain tumors can avoid radiotherapy and prolonged maintenance chemotherapy yet still achieve durable remission with this brief intensive chemotherapy regimen.

Overall survival benefit from tebentafusp in patients with best response of progressive disease.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9509-9509
Author(s):  
Anthony M. Joshua ◽  
Jean-Francois Baurain ◽  
Sophie Piperno-Neumann ◽  
Paul Nathan ◽  
Jessica Cecile Hassel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Safety Profile ◽  
Progressive Disease ◽  
Analysis Data ◽  
Cell Receptor ◽  
Kaplan Meier ◽  
Immortal Time Bias ◽  
Best Response ◽  
Overall Survival Benefit

9509 Background: Tebentafusp (tebe) is the first T cell receptor (TCR) therapeutic to demonstrate an overall survival (OS) benefit in a randomized Phase 3 (Ph3) study [ NCT03070392 ]. In Ph2, 42% of pts with best overall response (BOR) of progressive disease (PD) survived > 1 year (yr), suggesting RECIST-based radiographic assessments underestimate OS benefit of tebe. Here we analyzed OS in the Ph3 study in a cohort of pts with BOR of PD by comparing tebe to the control arm of investigator’s choice (IC). Methods: 378 pts were randomized in a 2:1 ratio to tebe vs. IC. BOR was assessed by investigators using RECIST v1.1. Treatment beyond first disease progression (TBP) was permitted for both arms. On the IC arm, only patients receiving pembrolizumab (pembro) continued with TBP and were included in the TBP-related analyses. No crossover to tebe was permitted; investigators were free to choose subsequent therapy. This analysis was conducted on the first interim analysis (data extracted Nov-2020). Kaplan-Meier estimates of OS were based on Day 100 landmark to eliminate immortal time bias and to capture majority of the PDs. Results: By Day 100, PD as BOR occurred in 52% (130/252) of tebe pts (PD-tebe) vs. 60% (76/126) of IC pts (PD-IC). Key baseline characteristics including lactate dehydrogenase, alkaline phosphatase, ECOG performance, age, and sex were similar between PD-tebe vs PD-IC. The proportion of pts with PD due to progression of target lesions (TL), non-TL, or new lesions were also similar between the two groups. More pts received TBP among PD-tebe 53% (69/130) vs PD-pembro 16% (10/61). Median duration of TBP was longer for PD-tebe (7 weeks) vs PD-Pembro (3 weeks). The safety profile of PD-tebe pts during TBP was similar to all tebe-treated pts. OS was superior for PD-tebe vs PD-IC, HR = 0.41 (95%CI 0.25-0.66), even when considering key baseline covariates. While some pts had regression of TL despite diagnosis of PD ( < 10% of pts), the OS benefit remained even when limited to pts with best change of tumor growth of TL, HR 0.46 (0.29, 0.73). 58% (75/130) PD-tebe and 52% (40/76) PD-IC pts received subsequent therapies. In a landmark OS analysis of these pts beginning on 1st day of subsequent therapy, prior tebe was associated with better OS vs. prior IC, HR 0.59 (95%CI 0.36-0.96). Conclusions: Tebe is the first TCR therapeutic to demonstrate an OS benefit in a solid tumor. Surprisingly, a strong OS benefit from tebe is observed even in pts with BOR of PD, suggesting that RECIST-based radiographic assessments do not capture the complete benefit from tebe. The safety profile of tebe during TBP was consistent with that for long-term tebe treatment. Clinical trial information: NCT03070392.

Survival Outcomes for Induction vs Adjuvant Chemotherapy in Squamous Cell Carcinoma of the Maxillary Sinus

2018 ◽  
Vol 160 (4) ◽  
pp. 658-663 ◽  
Author(s):  
Phoebe Kuo ◽  
Sina J. Torabi ◽  
Dennis Kraus ◽  
Benjamin L. Judson
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Maxillary Sinus ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Cox Regression ◽  
Rank Test ◽  
Controlled Clinical Trial ◽  
Log Rank Test ◽  
Kaplan Meier

Objective In advanced maxillary sinus cancers treated with surgery and radiotherapy, poor local control rates and the potential for organ preservation have prompted interest in the use of systemic therapy. Our objective was to present outcomes for induction compared to adjuvant chemotherapy in the maxillary sinus. Study Design Secondary database analysis. Setting National Cancer Database (NCDB). Subjects and Methods In total, 218 cases of squamous cell maxillary sinus cancer treated with surgery, radiation, and chemotherapy between 2004 and 2012 were identified from the NCDB and stratified into induction chemotherapy and adjuvant chemotherapy cohorts. Univariate Kaplan-Meier analyses were compared by log-rank test, and multivariate Cox regression was performed to evaluate overall survival when adjusting for other prognostic factors. Propensity score matching was also used for further comparison. Results Twenty-three patients received induction chemotherapy (10.6%) and 195 adjuvant chemotherapy (89.4%). The log-rank test comparing induction to adjuvant chemotherapy was not significant ( P = .076). In multivariate Cox regression when adjusting for age, sex, race, comorbidity, grade, insurance, and T/N stage, there was a significant mortality hazard ratio of 2.305 for adjuvant relative to induction chemotherapy (confidence interval, 1.076-4.937; P = .032). Conclusion Induction chemotherapy was associated with improved overall survival in comparison to adjuvant chemotherapy in a relatively small cohort of patients (in whom treatment choice cannot be characterized), suggesting that this question warrants further investigation in a controlled clinical trial before any recommendations are made.

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