scholarly journals ACT-03 Clinical outcome and radiological findings of patients with recurrent glioblastomas treated by bevacizumab

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii8-ii8
Author(s):  
Hajime Handa ◽  
Ichiyo Shibahara ◽  
Takuichiro Hide ◽  
Toshihiro Kumabe
Keyword(s):  
Clinical Outcome ◽  
Arterial Spin Labeling ◽  
Progressive Disease ◽  
Study Cohort ◽  
Newly Diagnosed ◽  
Radiological Findings ◽  
Double Positive ◽  
Median Period ◽  
High Age ◽  
Brain Barriers

Abstract Object: Seven years have passed since the approval of bevacizumab (BEV) in Japan. We retrospectively reviewed the clinical outcome and radiological findings of patients with recurrent glioblastomas (GB) treated by BEV. Method: We reviewed 116 patients, including 27 cases of newly diagnosed GB and 89 cases of recurrent GB, treated by BEV during the study period between 2013 June and 2019 September. Cumulatively, 116 patients received 1672 cycles of BEV. Among those, we focused on 74 patients with newly diagnosed GB treated by BEV at recurrence to examine clinical characteristics, outcome, and radiological findings of T2-circumscribed or double-positive proposed by Nowosieski et al. or Bahr et al., respectively. Result: The study cohort comprised median age of 66.8 years (range 10 to 81), median KPS of 60% (range, 20 to 100), median cycles of administration 11(1 to 59), median period of treatment 172 days (0 to 1413), median post-BEV survivals 266 days, and overall survival 693 days. Patients without progressive disease at 6 months post-BEV MRI (n = 23) presented favorable post-BEV survival of 713 days than those with progressive disease (n = 8) (p=0.0003). The radiological findings varied by patients, tumor lesions, and sequential imaging; thus, it was difficult to correlate with survival. Our data implied that the T2-circumscribed lesion was accompanied by no enhancement at T1 but hyperperfused at arterial spin labeling imaging, indicating that blood-brain barriers were intact and vascularization is activated. Conclusion: Although our cohort included patients with relatively high age, some had prolonged post-BEV survival. T2-circumscribed or double-positive was not useful to predict the survival; however, MRI at 6 months post-BEV can be an indicator for two years of post-BEV survival.

Chiasmatic optic glioma treated with chemotherapy

1985 ◽  
Vol 63 (6) ◽  
pp. 862-866 ◽  
Author(s):  
Jeffrey G. Rosenstock ◽  
Roger J. Packer ◽  
Larissa Bilaniuk ◽  
Derek A. Bruce ◽  
Jerri-Lynne Radcliffe ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Young Children ◽  
Progressive Disease ◽  
Actinomycin D ◽  
Initial Therapy ◽  
Optic Glioma ◽  
Newly Diagnosed ◽  
Content Type ◽  
Novel Approach ◽  
Clinical Stabilization

✓ Chiasmatic optic glioma is a rare tumor with an erratic natural history, usually seen in young children. A prior study from this institution demonstrated that these lesions were frequently lethal, despite initial clinical stabilization following radiation therapy, and that visual, intellectual, and late endocrinological disabilities were prevalent. A novel approach was developed in 1977, when an initial clinical response to vincristine was recorded in a child with a recurrent optic glioma. Since then, all children with recurrent optic glioma and all children aged 6 years old and under with newly diagnosed optic glioma have been offered a program of initial therapy with vincristine and actinomycin D for six cycles over 18 months. The four children with recurrent tumor who were treated with that regimen remain clinically stable 13 to 115 months after chemotherapy. Twelve children (eight under 24 months old) with newly diagnosed optic glioma have been treated with this program, and three are still on therapy. Four developed progression while on therapy, and five remain stable from 1 to 60 months posttherapy. The four children who developed progressive disease have been treated with radiation therapy and remain stable. Six of the 12 children showed shrinkage of their tumor on computerized tomography while receiving chemotherapy. This program may serve as an alternative to initial radiation therapy in young children.

scholarly journals Serum biomarkers and clinical characteristics of patients with Hodgkin lymphoma

2018 ◽  
Vol 75 (9) ◽  
pp. 911-917
Author(s):  
Olivera Simonovic ◽  
Milena Todorovic ◽  
Biljana Mihaljevic ◽  
Tatjana Stoimenov-Jevtovic ◽  
Ivan Petkovic ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Clinical Status ◽  
Scoring Systems ◽  
Control Group ◽  
Newly Diagnosed ◽  
Risk Patients ◽  
Tumor Environment ◽  
Prognostic Scoring Systems ◽  
The Relationship

Background/Aim. In classical Hodgkin?s lymphoma (cHL) the existing prognostic scoring systems do not include markers that adequately reflect the interaction of malignant Hodgkin and Reed-Sternberg (HRS) cells and tumor environment. The aim of this study was to determine the relationship between serum Galectin-1 (Gal-1) and soluble CD163 (sCD163) and the clinical status of patients with cHL, with special emphasis on the presence of relapse, progression, or resistance to the therapy applied. Methods. The research included 79 patients of whom 63 were patients with cHL, and the control group of 16 healthy volunteers. The study group of 63 patients with cHL included a subgroup of newly diagnosed patients without therapy, newly diagnosed patients with therapy, patients with relapse and progression of the disease and primary refractory patients during 2014 and 2015. Results. Analysis of the levels of sCD163 and Gal-1 within a group of patients suffering from cHL showed that the values of both molecules were higher in relapsed patients and the subgroup with progressive disease comparing to the subgroup of newly diagnosed patients without therapy or patients with therapy onset. Conclusion. Determination of Gal-1 and sCD163 levels is simple and reliable analysis that can contribute to the identification of high-risk patients with cHL and deserves inclusion in current prognostic scoring systems.

Abstract 577: Long Pentraxin 3: A New, Independent Marker of Mortality in Acute Chest Pain

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Frederic Kontny ◽  
Trygve Brügger-Andersen ◽  
Harry Staines ◽  
Heidi Grundt ◽  
Kyoko Miyamoto ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Chest Pain ◽  
Clinical Outcome ◽  
Risk Measures ◽  
Acute Chest Pain ◽  
Study Cohort ◽  
Pentraxin 3 ◽  
All Cause Mortality ◽  
Independent Marker

Long Pentraxin 3 (PTX3) is a newly identified member of the Pentraxin protein family that includes C-reactive protein (CRP). Unlike CRP, PTX3 is produced by the major cell types involved in atherosclerotic lesions in response to inflammatory stimuli. Increased PTX3 levels are found in acute coronary syndromes (ACS). Its role in long-term prediction of clinical outcome is, however, unknown. The aim of the current study was to assess the predictive value of PTX3 concerning all-cause mortality in patients hospitalized for acute chest pain. Plasma PTX3 was measured with a new, high-sensitive ELISA method (PPMX, Tokyo, Japan) in blood samples taken on admission in 784 patients admitted for acute chest pain suggestive of ACS. The patients were followed for 24 months concerning clinical outcome. For statistical analysis, the study cohort was divided into quartiles according to PTX3 levels. A multiple logistic regression model was fitted to include standard risk measures. At 24 months follow-up 121 patients had died. By logistic regression, the odds Odds Ratio for death among patients with highest PTX3 levels was 3.13 as compared to those with lowest levels (p=0.007) (table). Long Pentraxin 3 is a new, independent marker that strongly predicts long-term all-cause mortality in patients with acute chest pain.

scholarly journals Serum Levels of BAFF and APRIL Predict Clinical Response in Anti-PLA2R-Positive Primary Membranous Nephropathy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Giuseppe Stefano Netti ◽  
Barbara Infante ◽  
Federica Spadaccino ◽  
Giulia Godeas ◽  
Maria Grazia Corallo ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
B Cell ◽  
Immunosuppressive Therapy ◽  
Membranous Nephropathy ◽  
Partial Remission ◽  
Molecular Mechanisms ◽  
Serum Levels ◽  
Study Cohort ◽  
Baseline Serum ◽  
Entire Study

Primary membranous nephropathy (PMN) is a renal-specific autoimmune disease caused by circulating autoantibodies that target glomerular podocyte antigens (PLA2R/THSD7A). However, very little is known on the molecular mechanisms controlling B cell response in this nephropathy. The present study was aimed at correlating the serum levels of B cell activators BAFF/BLyS and APRIL with the presence of anti-PLA2R antibodies in PMN patients and with long-term clinical outcome. To this aim, 51 patients with anti-PLA2R-positive biopsy-proven PMN and nephrotic range proteinuria (>3.5 g/24 hours) were enrolled between January 2009 and December 2015 and treated with conventional 6-month immunosuppressive therapy. After 6 months, 29 patients (56.9%) cleared circulating anti-PLA2R, while in remaining 22 (43.1%), they persisted. Intriguingly, in the first group, baseline serum levels of BAFF/BLyS and APRIL were significantly lower than those in the second one. Moreover, after 6 months of immunosuppressive therapy, an overall reduction in both cytokine serum levels was observed. However, in PMN patients with anti-PLA2R clearance, this reduction was more prominent, as compared with those with anti-PLA2R persistence. When related to clinical outcome, lower baseline BAFF/BLyS (<6.05 ng/mL) and APRIL (<4.20 ng/mL) serum levels were associated with significantly higher probability to achieve complete or partial remission after 24-month follow-up. After dividing the entire study cohort into three groups depending on both cytokine baseline serum levels, patients with both BAFF/BLyS and APRIL below the cut-off showed a significantly higher rate of complete or partial remission as compared with patients with only one cytokine above the cut-off, while the composite endpoint was achieved in a very low rate of patients with both cytokines above the cut-off. Taken together, these results provide new insights into the role of BAFF/BLyS and APRIL in both the pathogenesis of anti-PLA2R-positive PMN and the response to immunosuppressive therapy.

scholarly journals Impact of elevated HbA1c on long-term mortality in patients presenting with acute myocardial infarction in daily clinical practice: insights from a ‘real world’ prospective registry of the Zwolle Myocardial Infarction Study Group

2019 ◽  
Vol 9 (6) ◽  
pp. 616-625 ◽  
Author(s):  
Renicus S Hermanides ◽  
Mark W Kennedy ◽  
Elvin Kedhi ◽  
Peter R van Dijk ◽  
Jorik R Timmer ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Clinical Outcome ◽  
Newly Diagnosed ◽  
Diagnosed Diabetes ◽  
Newly Diagnosed Diabetes ◽  
Long Term Mortality ◽  
Diabetes Patients

Background: Long-term clinical outcome is less well known in up to presentation persons unknown with diabetes mellitus who present with acute myocardial infarction and elevated glycosylated haemoglobin (HbA1c) levels on admission. We aimed to study the prognostic impact of deranged HbA1c at presentation on long-term mortality in patients not known with diabetes, presenting with acute myocardial infarction. Methods: A single-centre, large, prospective observational study in patients with and without known diabetes admitted to our hospital for ST-segment elevation myocardial infarction (STEMI) and non-STEMI. Newly diagnosed diabetes mellitus was defined as HbA1c of 48 mmol/l or greater and pre-diabetes mellitus was defined as HbA1c between 39 and 47 mmol/l. The primary endpoint was all-cause mortality at short (30 days) and long-term (median 52 months) follow-up. Results: Out of 7900 acute myocardial infarction patients studied, 1314 patients (17%) were known diabetes patients. Of the 6586 patients without known diabetes, 3977 (60%) had no diabetes, 2259 (34%) had pre-diabetes and 350 (5%) had newly diagnosed diabetes based on HbA1c on admission. Both short-term (3.9% vs. 7.4% vs. 6.0%, p<0.001) and long-term mortality (19% vs. 26% vs. 35%, p<0.001) for both pre-diabetes patients as well as newly diagnosed diabetes patients was poor and comparable to known diabetes patients. After multivariate analysis, newly diagnosed diabetes was independently associated with long-term mortality (hazard ratio 1.72, 95% confidence interval 1.27–2.34, P=0.001). Conclusions: In the largest study to date, newly diagnosed or pre-diabetes was present in 33% of acute myocardial infarction patients and was associated with poor long-term clinical outcome. Newly diagnosed diabetes (HbA1c ⩾48 mmol/mol) is an independent predictor of long-term mortality. More attention to early detection of diabetic status and initiation of blood glucose-lowering treatment is necessary.

scholarly journals SURG-02. LASER INTERSTITIAL THERMAL THERAPY FOR BRAIN METASTASES: OUTCOMES AND PREDICTORS OF LOCAL RECURRENCE

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i31-i31
Author(s):  
Dhiego Bastos ◽  
Ganesh Rao ◽  
Isabella Glitza ◽  
Jonathan Loree ◽  
Jeffrey S Weinberg2 ◽  
...  
Keyword(s):  
Local Recurrence ◽  
Brain Metastases ◽  
Systemic Therapy ◽  
Protective Factor ◽  
Progressive Disease ◽  
Cox Regression ◽  
Radiation Necrosis ◽  
Newly Diagnosed ◽  
Predicting Factors ◽  
Risk Of Treatment

Abstract BACKGROUND: LITT has been used to treat recurrent brain metastasis after stereotactic radiosurgery (SRS). Little is known about how best to assess the efficacy of treatment, specifically the ability of LITT to control local tumor progression post-SRS. Objectives: Evaluate the predictive factors associated with local recurrence after LITT. METHODS: Retrospective study with consecutive patients with brain metastases treated with LITT. Based on radiological aspects, lesions were divided into progressive disease after SRS (recurrence or radiation necrosis) and new lesions. Primary endpoint was time to local recurrence. RESULTS: 61 consecutive patients with 82 lesions (5 newly diagnosed, 46 recurrence and 31 radiation necrosis). Freedom from local recurrence at 6 months was 69.6%, 59.4% at 12, and 54.7% at 18 and 24 months. Incompletely ablated lesions had a shorter median time for local recurrence (p&lt; 0.001). Larger lesions (&gt;6cc) had shorter time for local recurrence (p=0.03). Dural based lesions showed a shorter time to local recurrence (p=0.01). Tumor recurrence/newly diagnosed had shorter time to local recurrence when compared to RN lesions (p=0.01). Patients receiving systemic therapy after LITT had longer time to local recurrence (p=0.01). In multivariate Cox-regression model the HR for incomplete ablated lesions was 4.88 (p&lt; 0.001), 3.12 (p=0.03) for recurrent tumors, and 2.56 (p=0.02) for patients not receiving systemic therapy after LITT. Complication rate was 26.2%. CONCLUSIONS: Incompletely ablated and recurrent tumoral lesions were associated with higher risk of treatment failure and were the major predicting factors for local recurrence. Systemic therapy after LITT was a protective factor regarding local recurrence.

Genetic Polymorphisms Associated with Clinical Outcome in the Intergroup Trial S9321, Comparing High Dose Therapy with Standard Dose Therapy for Myelomaon, on Behalf of ECOG, SWOG, CALGB, and the Bank on a Cure.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1495-1495
Author(s):  
Rafael Santana-Davila ◽  
John Crowley ◽  
Brian Durie ◽  
Bart Barlogie ◽  
Philip Greipp ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Genetic Polymorphisms ◽  
Median Survival ◽  
Dose Regimen ◽  
Standard Dose ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Dose Therapy ◽  
Intergroup Trial

Abstract Genetic variations in patient populations likely contribute to disease progression and therapeutic outcomes. We have begun a systematic approach to examine the association of genetic variations (ie. functional, single nucleotide polymorhisms, SNPs) involved in myeloma growth promotion, metabolic events, drug responses, and DNA repair on clinical outcome in the intergroup trial S9321. This trial tested a single high dose regimen with autologous stem cell support against a conventional dose regimen, with further randomization of responders to maintenance with interferon or not, in newly diagnosed patients with multiple myeloma. ECOG, CALGB and SWOG enrolled 899 patients with newly diagnosed MM to receive VAD induction x 4 cycles followed by randomization to PBSC-supported high dose therapy (HDT) versus standard dose therapy (SDT) of VBMCP, using CTX 4.5 g/m2 + G-CSF for PBSC mobilization in all patients. Responders to VBMCP or HDT were randomized to IFN or no maintenance. Specimens were distributed through ECOG for biologic correlative studies, including candidate SNP analysis. SNP assays have been developed using the Sequenom Mass-extend platform for functional SNPs in IL-6, IL-1, IL-RA, IL-10, TNF, Lta, TGFb, MDR1, MPO, CYP3A4, GST (M, P, T), ERCC2 and XRCC1, and are being evaluated on 803 DNA samples prepared from patients enrolled in S9321. Preliminary findings (n=135) demonstrate functional genetic variants of IL-10 (position -1082), IL-1 (position +3953), TGFb (postion -509), and TNFa (position -308) are showing trends associated with differences in progression free survival; and variants in IL-6 (position -174) are associated with response. Median survival of the IL-10 variants was 31 months for A/A low producer alleles versus 19 months for the G/G high producer alleles (p=.5). For TNFa, 2 cases with the high producer A/A alleles died within a year, while the median survival for the lower producer G/G alleles was 2 years (p=.04). For patients with the high producer C/C/ allele of IL-1 (n=67), median survival was 2 years, versus 5 patients with the T/T low producer alleles that had a median survival greater than 5 years (preliminary p=.29). While these preliminary results are now only suggestive of trends in genetic polymorphisms associated with clinical outcome, completion of the full SNP panel on the entire sample base should provide a extensive association study, and analysis of potential differences in therapy arms of the trial. The full panel and association studies will be presented.ααββααα

A Phase II Study of PS-341 for Patients with High Risk, Newly Diagnosed Multiple Myeloma: A Trial of the Eastern Cooperative Oncology Group (E2A02).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2546-2546 ◽  
Author(s):  
Angela Dispenzieri ◽  
Emily Blood ◽  
David Vesole ◽  
Rafael Fonseca ◽  
Natalie Callander ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Peripheral Neuropathy ◽  
High Risk ◽  
Partial Response ◽  
Progressive Disease ◽  
Response Rate ◽  
Cell Labeling ◽  
Newly Diagnosed ◽  
Grade 3

Abstract Background: Multiple myeloma (MM) is an incurable disease with a anticipated overall survival (OS) ranging from months to decades. Modest improvements in OS have been made with high-dose chemotherapy with peripheral blood stem cell transplant (PBSCT), but to date prognostic factors have a greater impact on OS than do individual therapies. Patients with adverse risk factors such as elevated beta-2 microglobulin (B2M), plasma cell labeling index, deletions of the long arm of chromosome 13 by metaphase cytogenetics (del 13q) require innovative new treatment strategies. Bortezomib has significant activity in patients with both newly diagnosed and relapsed/refractory MM, but its specific role in patients with adverse features has not yet been defined. Methods: Patients with newly diagnosed “high-risk” myeloma (B2M ≥ 5.5., PCLI ≥ 1, or del 13q) and adequate organ and functional status were eligible. Patients were treated with bortezomib 1.3 mg/m2 day 1, 4, 8, and 11 every 21 days for 8 cycles as induction. After induction, patients were scheduled to receive bortezomib 1.3 mg/m2 every other week indefinitely. Elective peripheral stem cell mobilization (growth factor alone) was allowed after 4 cycles of bortezomib. Patients relapsing on maintenance schedule were to have the full induction schedule resumed. Responses were by the EBMT criteria but a very good partial response category was included. The primary end-point was the response rate in these high-risk patients (90% power to detect a response rate of 50% or higher). The study decision rule requires that 16 or more responses, among 39 eligible patients, are seen in order to declare this treatment effective. Results: Between March 15, 2004 and March 10, 2005, 44 patients enrolled on study. Among the 43 eligible patients, median age was 63; 51% were male. All patients had high risk disease: del 13q (6/41); plasma cell labeling index ≥1% (16/34); and B2M≥5.5 (34/43). Preliminary response data are available for 18 of the 44 cases enrolled, of which 7 had partial response, 1 had minimal response, 1 had no response, 2 had progressive disease, and 5 were unevaluable. Among those patients completing induction therapy and with response information, the median number of cycles of therapy administered is 5, range (0,8). The most common non-hematologic adverse events (AEs) of grade 3 or higher included hyponatremia (9 patients) and diarrhea (6 patients). Mild sensory peripheral neuropathy was common: grade 1, 16 patients; grade 2, 2 patients. Only 1 patient had grade 3 peripheral neuropathy. One patient died after receiving 2 doses bortezomib due to heart block and asystole. Two patients had a grade 4, 25 patients had grade 3, and 13 had grade 1 or 2 as the worst grade non-hematologic adverse event. Based on data received by August 1, 2005, 18 patients have gone off study: AEs (2); death (1); progressive disease (9); and other reasons (6). Updated results on the full study population along with FISH data for IgH translocations and deletions of 13q and 17p will be presented at the meeting. Conclusions: Preliminary results suggest that upfront bortezomib has activity in patients with high-risk MM, but further follow-up is required.

The Efficacy of the FLT3 Inhibitor Lestaurtinib in AML Depends on Adequate Plasma Inhibitory Activity (PIA), and Is Unaffected by Rising FLT Ligand Levels: An Update of the NCRI AML15 & 17 Trials

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 421-421
Author(s):  
Steven Knapper ◽  
Paul White ◽  
Mark J. Levis ◽  
Robert K Hills ◽  
Nigel H. Russell ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Outcome ◽  
Tyrosine Kinase ◽  
Relapse Rate ◽  
Inhibitory Activity ◽  
Newly Diagnosed ◽  
Off Label Use ◽  
Off Label ◽  
Flt3 Mutations ◽  
Label Use

Abstract Abstract 421 The receptor tyrosine kinase FLT3 remains the subject of intense clinical interest as a therapeutic target in AML. FLT3-activating mutations are seen in one-third of adults at diagnosis and are associated with adverse prognosis. The multi-targeted kinase inhibitor lestaurtinib (CEP701) has potent activity against FLT3. In monotherapy studies, sustained plasma drug activity sufficient to inhibit FLT3 by >85% was found to be a prerequisite for clinical response (1,2). A recently-reported randomized study of lestaurtinib combined with chemotherapy in relapsed FLT3-mutated AML failed to demonstrate improved clinical outcome with lestaurtinib, but definitive conclusions were limited by the relatively low rate (58%) of patients achieving >85% FLT3 inhibition (3). In that study, rising levels of FLT3 ligand (FL) were noted during chemotherapy; raised FL levels have been reported to impede the in vitro efficacy of FLT3 inhibitors (4). As part of an ongoing randomised assessment (NCRI AML15 and 17 Trials) 118 newly-diagnosed FLT3-mutated non-APL AML patients (median age 49 [range 16–66], 86 ITD, 30 TKD point mutation, 2 both FLT3 mutations, 87% intermediate risk karyotype) received lestaurtinib for up to 28 days following each of 4 courses of chemotherapy. Based on early pharmacokinetic data, starting dose of lestaurtinib was adjusted according to concomitant anti-fungal drug use: 40mg bid in azole treated patients, 80mg bid in other patients. Patients received a median 3 courses of lestaurtinib (range 0–4); no excess severe adverse events have been reported in lestaurtinib-treated patients. Median follow-up is now 30 months (range 9–47). 49 patients underwent allogeneic SCT (37 in 1st CR, 28 myeloablative conditioning, 21 RIC). In a non-randomised comparison of clinical outcome with a matched historical age-matched control population of 118 FLT3-mutated patients entering the AML15 Trial prior to the opening of the lestaurtinib randomisation, there was a modest improvement in complete remission (CR/CRi) rate (92% vs 90% historical control), 2-year cumulative relapse rate (47% vs 55%) and 2-year overall survival (50% vs 47%). Trough FLT3 plasma inhibitory activity (PIA) was measured on day 14 of each lestaurtinib course. 169 timepoints were assessed in 84 patients with 88% of patients achieving at least 1 FLT3 PIA measurement of >85%. FLT3 PIA of >85% was seen at 75% of individual timepoints (127/169). Rates of relapse were significantly lower in patients that achieved FLT3 PIA>85% at all evaluated timepoints: the 2-year relapse rate was 38% in inhibited vs 61% in non-inhibited patients (22/58 vs 16/26) (p=0.01) where results were available for 1 or more timepoints, 23 vs 58% (6/28 vs 10/18)(p=0.01) for 2 or more timepoints and 15% vs 64% (2/14 vs 7/11)(p=0.007) for 3 or more timepoints. Significantly increased 2-year overall survival was seen in patients that achieved >85% PIA at 1 or more timepoints, 64% in inhibited vs 40% in non-inhibited patients (37/58 vs 10/26)(p=0.01). Mean day 14 FL concentrations rose through successive courses of lestaurtinib treatment from 529 pg/ml during course 1 to 1350 pg/ml, 2575 pg/ml and 2467 pg/ml respectively during courses 2,3 and 4. No increase was seen in alpha-1-acid glycoprotein levels. Despite rising FL levels, no fall off was seen in achievement of FLT3 inhibition: day 14 FLT3 PIA>85% was achieved by 75% of assayed patients during course 1 (51/68), 80% during course 2 (39/49), 78% during course 3 (25/32) and 60% during course 4 (12/20). No difference was seen in FLT3 PIA between patients grouped according to high or low FL concentration. These data provide evidence of an emerging relationship between sustained FLT3 inhibition and improved clinical outcome when tyrosine kinase inhibition is combined with standard chemotherapy in newly diagnosed AML. Rising FL levels through successive courses of therapy failed to impede target inhibition. The sequential combination of lestaurtinib with chemotherapy continues to be evaluated in the ongoing randomized NCRI AML17 Trial. Disclosures: Off Label Use: The presentation will include discussion of the off-label use of lestaurtinib (CEP701) in the treatment of newly-diagnosed AML patients with FLT3 mutations.

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