scholarly journals High Risk Older AML Patients May be Benefited from the Treatment of Decitabine Combined Wih CAG Regimens

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4953-4953
Author(s):  
Xia Xiao ◽  
Mingfeng Zhao ◽  
Qi Deng ◽  
Qing Li ◽  
Juan Mu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Adverse Events ◽  
Older Patients ◽  
Median Overall Survival ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Ecog Performance Status ◽  
Secondary Aml ◽  
Number Of Patients

Abstract Patients over age 60 maked up more than 50% of newly diagnosed patients with acute myeloid leukemia (AML). Futhermore, with an aging population, more and more older AML patients were diagnosed in China. But the treatment approaches of this disease were variable, with many uncertainties and controversies. Treatment options for older patients with adverse prognostic features, such as poor performance status, unfavorable cytogenetics or an antecedent hematologic disorder were limited, and outcomes were poor. Aggres­sive induction chemotherapy had a high mortality and relatively low efficacy in this population. There were several new therapeutic schemes for older patients with AML. CAG regimens consisting of low-dose cytarabine, aclarubicin and granulocyte-colony stimulating factor for the treatment of older patients with AML showed higher rates of CR (42-68%). Decitabine, a DNA-hypomethylating agent induces differentiation and apoptosis of leukemic cells. The current National Comprehensive Cancer Care guidelines suggested decitabine as alterative options for older patients with AML. Previous studies have shown that decitabine demonstrated efficacy in a phase II multicenter study of older patients with AML, with a CR rate of 25%, 30-day mortality of 7%, median overall survival 7.7 months and little extramedullary toxicity. In our study, decitabine(15 mg/m2/d, d1-5) combined with CAG regimens (aclarubicin 20 mg/d, d3-6, Ara-C 10 mg/m2, q12h, d3-9, G-CSF 300ug, qd, d1-9) treated 27 older patients with AML, repeated every 4 weeks. Effectiveness and safety were assessed. 27 older patients with newly diagnosed AML who were in Tianjin First Central Hospital of China from January 2011 to December 2013 were enrolled in our study. They were all treated with decitabine combined with CAG regimens. The characteristics of the 27 patients were described in Table I. The study population included 15 males and 12 females, with a median age of 68 years (range 60-79 years). All patients had Eastern Cooperative Oncology Group (ECOG) performance status of <3. Cytogenetics were classified according to criteria of the Cancer and Leukemia Group B(CALGB), and were adverse in 11 patients (40.7%) and intermediate in 16 patients (59.3%). No patient had favorable cytogenetics. 12 patients (44.4%) had secondary AML or an antecedent MDS or myeloproliferative disorder. Molecular diagnostics with mutations of FLT3-ITD in 6 patients (22.2%), NPM1 in 7 patients (25.9%) patients and JAK-2 in 4 patients (14.8%). Clinical responses, survival and adverse events of all 27 patients were analyzed. The median treatment cycle was 4 cycles. Rate of complete remission, overall response rate and a 30-day mortality rate were 40.1%, 66.7%, 7.4%, respectively. The median overall survival and median recurrence-free survival were 13.0months (95%CI, 7.0-18.0 months ) and 7.0 months (95%CI, 3.0-11.0 months), respectively. Adverse events in the regimens were mainly included myelosuppression, infection, nausea, vomiting and liver dysfunction. The adverse events could be well tolerated after managements. In conclusion, the treatment of decitabine combined with CAG regimens was found to be feasible and useful in high-risk older patients with AML. This regimen was a well-tolerated therapeutic alternative, was effective in producing remissions lasting several months or disease stabilization in high-risk older patients with AML. Table 1. The characteristics of newly diagnosed patients with AML Total number of patients n=27 median age(range) 68 years(60-79 years) Male/female 15/12 (1.25/1) ECOG performance status, n (%) 0 5 (18.5%) 1 10 (37.0%) 2 12 (44.4%) Cytogenetics, n (%) Adverse 11 (40.7%) Intermediate 16 (59.3%) secondary AML, n (%) MDS 6 (22.2%) myeloproliferative 5 (18.5%) Other tumors 1 (3.7%) Molecular mutations, n (%) FLT3-ITD 6 (22.2%) NPM1 7 (25.9%) JAK-2 4 (14.8%) Disclosures No relevant conflicts of interest to declare.

A Phase II Study Of Tosedostat (TST) In Combination With Either Cytarabine Or Decitabine In Newly Diagnosed Older Patients With Acute Myeloid Leukemia (AML) Or High-Risk Myelodysplastic Syndrome (MDS)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3926-3926
Author(s):  
Raya Mawad ◽  
Pamela S. Becker ◽  
Paul C. Hendrie ◽  
Bart L Scott ◽  
Brent L. Wood ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Older Patients ◽  
Hematopoietic Cell Transplantation ◽  
Controlled Trial ◽  
Performance Status ◽  
Newly Diagnosed ◽  
Open Label ◽  
Ecog Performance Status ◽  
To Receive

Abstract Background Treatment outcomes for older patients with newly diagnosed AML remain poor. TST is an oral aminopeptidase inhibitor that has anti-neoplastic activity in a variety of malignancies, including AML. Phase I/II monotherapy studies in patients with relapsed AML and MDS have shown TST to have adequate safety and promising efficacy. Pre-clinical AML blast proliferation assays have demonstrated synergy between TST and both cytarabine and hypomethylating agents. For this reason, we performed a randomized, open-label Phase II trial using TST in combination with intermediate-dose cytarabine or decitabine in patients with untreated AML or high-risk MDS (i.e. RAEB-2). Methods Patients ≥60 years old with untreated AML or high risk MDS were randomized to receive TST 120 mg daily by mouth days 1-21 with 5 days of either cytarabine 1 g/m2/day IV or decitabine 20 mg/m2/day IV delivered every 35 days. Patients received up to three 35-day cycles if they had at least stable disease with an acceptable toxicity profile following the initial course. Patients who did not achieve a complete remission (CR) or CR with incomplete blood count recovery (CRi) after 3 cycles of therapy were taken off study; patients who obtained CR/CRi were eligible to receive up to 2 additional cycles (maximum of 5). The primary objective was to determine the rates of CR and 4 month survival using TST in combination with either cytarabine or decitabine for older patients with untreated AML or high-risk MDS. Results A total of 26 patients have been treated, with 14 receiving TST/cytarabine and 12 receiving TST/decitabine. The median age was 69 (range, 60-83), and 22 patients (85%) presented with an ECOG performance status of 1. Nineteen patients (73%) had AML and 7 (27%) had MDS RAEB-2. Nineteen patients (73%) had intermediate-risk and 7 (27%) had adverse-risk disease by European Leukemia Net criteria. Fourteen patients (54%) had secondary AML/MDS or antecedent hematologic disorder. The median duration of treatment was 3 months. The overall CR/CRi rate was 54%, with 10 patients (39%) achieving a CR and 4 patients (15%) achieving a CRi. Five patients required 3 cycles, four patients required 2 cycles and five patients required 1 cycle of therapy to achieve maximal disease response. CR/CRi was attained in 3 patients with adverse cytogenetics and 4 additional patients with FLT3 mutations. Of the 14 patients who achieved a CR/CRi (54%), 7 were treated on each of two study arms. Nine of the 14 patients who achieved a CR/CRi were referred for allogeneic hematopoietic cell transplantation (HCT), 3 patients deferred HCT, and 1 patient died of sepsis in CRi 133 days after starting induction. Ten patients were taken off study after a median of 2 cycles due to lack of response or disease progression. With a median follow-up of 5.7 months (range, 0.5-13.4), 21 patients (81%) lived longer than 4 months. Five (19%) of the 26 patients died within 4 months of starting therapy. Of these five patients, three died of sepsis on subsequent salvage protocols, one with a history of myeloproliferative disorder died of splenic infarct within 15 days of starting therapy and a fifth patient died at age 83 during cycle 2 of unknown cause. Eight patients (31%) were treated completely as outpatients without requiring hospitalization, and 15 patients (58%) were hospitalized at some point during treatment for febrile neutropenia. There were no Grade 3-4 non-hematologic toxicities requiring withdrawal from the study. Conclusions These results demonstrate that TST at 120 mg daily in combination with cytarabine or decitabine resulted in a 54% CR/CRi rate in 26 older patients with untreated AML or high-risk MDS. This approach was well tolerated as predominantly outpatient therapy and may warrant further study in a controlled trial. Disclosures: Wang: Cell Therapeutics, Inc.: Employment. Myint:Cell Therapeutics, Inc: Employment. Singer:Cell Therapeutics, Inc: Employment, Equity Ownership.

Initial experience of TAS-102 chemotherapy in Australian patients with chemorefractory metastatic colorectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 71-71
Author(s):  
Azim Jalali ◽  
Hui-Li Wong ◽  
Rachel Wong ◽  
Margaret Lee ◽  
Lucy Gately ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Febrile Neutropenia ◽  
Metastatic Colorectal Cancer ◽  
Real World ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Ecog Performance Status ◽  
Number Of Patients

71 Background: For patients with refractory metastatic colorectal cancer (mCRC) treatment with Trifluridine/Tipiracil, also known as TAS-102, improves overall survival. In Australia, TAS-102 was initially made available locally through patients self-funding, later via an industry sponsored Medicine Access Program (MAP) and then via the Pharmaceutical Benefits Scheme (PBS). This study aims to investigate the efficacy and safety of TAS-102 in real world Australian population. Methods: A retrospective analysis of prospectively collected data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was undertaken. The characteristics and outcomes of patients receiving TAS-102 were assessed and compared to all TRACC patients and those enrolled in the registration study (RECOURSE). Results: Across 13 sites, 107 patients were treated with TAS-102 (non-PBS n = 27, PBS n = 80), The median number of patients per site was 7 (range: 1-17). The median age was 60 years (range: 31-83), compared to 67 for all TRACC patients and 63 for RECOURSE. Comparing registry TAS-102 and RECOURSE patients, 75% vs 100% were ECOG performance status 0-1, 74% vs 79% had initiated treatment more than 18 months from diagnosis of metastatic disease and 39% vs 49% were RAS wild type. Median time on treatment was 10.4 weeks (range: 1.7-32). Median clinician assessed progression-free survival was 3.3 compared to RECIST defined PFS of 2 months in RECOURSE study, while median overall survival was the same at 7.1 months. Two patients (2.3%) had febrile neutropenia and there were no treatment-related deaths in the real-world series, where TAS102 dose at treatment initiation was at clinician discretion. In the RECOURSE study there was a 4% febrile neutropenia rate and one treatment-related death. Conclusions: TRACC registry patients treated with TAS102 were younger than both TRACC patients overall and those from the RECOURSE trial. Less strict application of RECIST criteria and less frequent imaging may have contributed to an apparently longer PFS. However overall survival outcomes achieved with TAS102 in real world patients were comparable to findings from this pivotal trial with an acceptable rate of major adverse events.

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.

Assessment of radioembolization among patients who met the inclusion criteria for Sorafenib Hepatocellular Carcinoma Assessment Randomized Protocol (SHARP).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14654-e14654 ◽  
Author(s):  
Bruno Sangro ◽  
Livio Carpanese ◽  
Roberto Cianni ◽  
Daniele Gasparini ◽  
Rita Golfieri ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Liver Function ◽  
Median Overall Survival ◽  
Performance Status ◽  
Advanced Hepatocellular Carcinoma ◽  
Inclusion Criteria ◽  
Ecog Performance Status ◽  
Advanced Hcc ◽  
Good Liver Function

e14654 Background: SHARP was pivotal in determining the safety and efficacy of sorafenib in advanced hepatocellular carcinoma (HCC) in patients with predominately good liver function. In practice, many patients with advanced HCC receive radioembolization (RE). Investigators from the European Network on RE with yttrium-90 resin microspheres (ENRY) group conducted an analysis of safety and survival among consecutive patients who met the SHARP inclusion criteria. Methods: 58% of patients (189 of 325) who had received RE between 09/2003 and 12/2009 were considered SHARP-equivalents. Of these, 11.6% received sorafenib 4.7 months (median) after RE for a median duration of 2.8 months. Safety and tolerability analyses were conducted up to day 90 post RE; changes from baseline were recorded and transitions in CTCAE grades >3 tested. Statistical analyses used SAS (SAS, Cary NC) version 9.2 XP Pro. Results: Like the SHARP sorafenib cohort, most patients had advanced HCC (BCLC stage C: 72.5%), good liver function (Child–Pugh class A: 100%) and ECOG performance status (0–1: 90.5%). Macroscopic vascular invasion (MVI), extrahepatic spread (EHD) or both was present in 33.9%. 20.1% had received prior surgical procedures, 8.5% prior ablative procedures and 33.3% prior vascular [chemo]embolization. RE was predominantly a single whole-liver procedure (median activity 1.7 GBq). Median overall survival was 10.8 months (95% CI: 8.8–12.8) in the SHARP-equivalent cohort, 10.2 months (8.3–11.8) in patients with MVI/EHD, 9.7 months (7.6–10.9) in advanced HCC (BCLC stage C) and 16.6 months (11.2–22.8) in intermediate HCC (BCLC stage B). Treatment-related adverse events (all grades; grade >3) were: fatigue (50.3%; 2.1%), abdominal pain (25.9%; 2.1%), nausea/vomiting (31.2%; 0.5%) and GI ulcer (3.2%; 1.0%). At baseline, raised bilirubin (all grades) was present in 20.3%, increasing to 49.4% of patients evaluated up to day 90. Bilirubin grade was unchanged in 58.1% and increased in 37.8%; 4.0% had ≥grade 3 events. Conclusions: In patients matching the inclusion criteria for SHARP, RE was well tolerated with a median overall survival which compares favorably with sorafenib.

scholarly journals External Validation of the Impede VTE Risk Score in Newly Diagnosed Multiple Myeloma (MM) Patients

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3148-3148 ◽  
Author(s):  
Fahrettin Covut ◽  
Ramsha Ahmed ◽  
Christy J. Samaras ◽  
Faiz Anwer ◽  
Alex V. Mejia Garcia ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Cumulative Incidence ◽  
Systemic Treatment ◽  
Femur Fracture ◽  
Performance Status ◽  
External Validation ◽  
Risk Groups ◽  
Newly Diagnosed ◽  
Ecog Performance Status

Background: Venous thromboembolism (VTE) is a prevalent cause of morbidity in MM patients. The IMPEDE VTE score was recently proposed by Sanfilippo KM et al. in 2018 ASH annual meeting to predict VTE in MM. Herein, we report on the external validation of this score. Methods: We reviewed consecutive newly diagnosed MM patients who were treated at the Cleveland Clinic between 2010 and 2012. All treatment variables were collected as time-varying variables. Poor cytogenetic features were defined as monosomy 13 or 17, t(4;14), or t(4;16). We calculated the total IMPEDE VTE score for each patient as previously defined; immunomodulatory drug (IMiD) use (+3), BMI >25 kg/m2 (+1), pathologic pelvis/femur fracture (+2), erythropoiesis-stimulating agent use (+1), low/high dexamethasone use (+2/+4), doxorubicin use (+2), Asian race (-3), history of VTE (+3), central venous catheter use (+2), prophylactic aspirin or enoxaparin (-2), therapeutic anticoagulation (-5). Patients with IMPEDE VTE score of <3, 3 to 6, and >6 were defined as low-, intermediate-, and high-risk groups, respectively. Cumulative incidence of symptomatic VTE after initiation of systemic treatment was calculated with death as competing risk and compared with the Gray's test. Overall survival (OS) was estimated by the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox analysis was used to identify independent predictors of OS. Results: We identified 210 MM patients, 102 (49%) were female, 31 (15%) were black, and median age at diagnosis was 63 years (range: 30 - 91). Fifteen (7%) patients had VTE prior to MM diagnosis and 30 (14%) patients had pathologic pelvic or femur fracture at or after MM diagnosis. Poor cytogenetic features were seen in 65 (31%) patients. ECOG performance status at diagnosis was ≥2 for 33 (16%) patients. Sixty-seven (32%), 65 (31%), and 57 (27%) patients had ISS stage I, II, and III disease, respectively. MM subtypes were IgG, IgA, and light-chain disease for 109 (52%), 46 (22%), and 52 (25%) patients, respectively. IMiDs and low-dose dexamethasone were given to 145 (69%) and 205 (98%) patients, respectively. Seventy-seven (37%) patients underwent autologous hematopoietic cell transplant. Patient and treatment characteristics were compared between patients with and without VTE after MM diagnosis in Table 1. Twenty-two (10%) patients had symptomatic VTE within 6 months after initiation of systemic treatment for MM. When IMPEDE VTE score was calculated based on the risk factors during this time period, 37 (18%), 157 (75%), and 16 (8%) patients were in low-, intermediate- and high-risk groups, respectively. Six-months cumulative incidence of VTE in low-, intermediate- and high-risk groups were 2.7% (95% CI: 0 - 7.9), 10.8% (95% CI: 6.0 - 15.7), and 25% (95% CI: 3.8 - 46.2), respectively (p=0.011) (Figure 1A). Whereas, 39 (19%) patients were diagnosed with symptomatic VTE during median follow-up of 86 months. When the highest IMPEDE VTE score for each patient was calculated based on the risk factors at any time after initiation of treatment, 16 (8%), 151 (72%), and 43 (20%) patients were in low-, intermediate-, and high-risk groups, respectively. Seven-year cumulative incidence of VTE in low-, intermediate- and high-risk groups were 9.0% (95% CI: 0 - 25.7), 16.3% (95% CI: 10.3 - 22.3), and 29.3 (95% CI: 15.2 - 43.3), respectively (p=0.014) (Figure 1B). Seven-year OS of patients with and without VTE within 6 months after initiation of treatment was 50% (95% CI: 32% - 79%) and 46% (95% CI: 39% - 55%), respectively (p=0.4). On multivariable analysis, VTE vs no VTE within 6 months after initiation of treatment did not predict OS (HR 1.10, 95% CI: 0.46 - 2.66, p=0.8), whereas each 1-year increase in age (HR 0.99, 95% CI: 0.96 - 1.02, p=0.61), each 1 increase in ECOG performance status (HR 1.77, 95% CI: 1.24 - 2.53, p=0.002) and ISS stage (HR 1.50, 95% CI: 1.06 - 1.14, p=0.024), poor vs non-poor cytogenetics features (HR 4.38, 95% CI: 2.25 - 8.57, p<0.0001), high vs normal LDH (HR 1.94, 95% CI: 1.05 - 3.60, p=0.035), IMiD use vs non-use at first induction (HR 0.52, 95% CI: 0.29 - 0.43, p=0.026), and transplant vs no transplant (HR 0.40, 95% CI: 0.20 - 0.79, p=0.008) were statistically significant predictors of OS (Table 2). Conclusion: In this cohort of MM patients, we showed that IMPEDE VTE score was able to stratify patients into distinct risk groups and can be a helpful tool to provide personalized strategies for thromboprophylaxis. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Valent:Takeda pharmaceuticals: Speakers Bureau; Amgen corporation: Speakers Bureau; Celgene corporation: Speakers Bureau.

P14.76 Bevacizumab (BEV) alone or in combination with chemotherapy in recurrent Glioblastoma Multiforme (GBM): A real world experience

2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii52-ii52
Author(s):  
H I Chalchal ◽  
T Zhu ◽  
C Woitas ◽  
S Ahmed ◽  
O Souied ◽  
...  
Keyword(s):  
Overall Survival ◽  
Glioblastoma Multiforme ◽  
Real World ◽  
Performance Status ◽  
P Value ◽  
Ecog Performance Status ◽  
Number Of Patients ◽  
Significant Difference ◽  
Historic Control ◽  
Recurrent Gbm

Abstract BACKGROUND Patients with glioblastoma multiforme (GBM) have a median survival of about 14 months. In recurrent GBM no active intervention has shown improvement in survival. Clinical trials has shown that bevacizumab (BEV) alone or in combination with chemotherapy is associated with better progression free survival (PFS). The current study aims to assess efficacy of BEV in real-world setting. MATERIAL AND METHODS Population-based retrospective cohort study patients with recurrent GBM diagnosed in the province of Saskatchewan during 2008–2018 and received BEV alone or in combination with chemotherapy were evaluated. Survival was compared with historic control. RESULTS 43 eligible patients with GBM treated with BEV with or without chemotherapy. 25 patients were treated with Bev alone and 18 patients treated with chemotherapy+ BEV. Median age of the patients were noted to be 53 years. 28 male, and 15 female. 80% of patients treated with single agent BEV had a performance status of either 2 or 3 compared to 33% of patient treated with BEV+ chemotherapy. Median PFS was 4.6 months with 95% CI 2.9–6.9. Median Overall survival (OS) from the time of diagnosis was 17.5 month. Median OS from the time of start of BEV was 5.4 months with 95% CI 3.4–6.8. Partial response (PR) was noted in 3 patients (7%) with stable disease (SD) in 6 patients (14%). 33 (77%) had progressive disease (PD). We were unable to confirm response status in one patient (2%). No statistically significant difference in response rate for patients treated with BEV and BEV+ Chemotherapy. From the start of Bev to the best response, 11 patients (30.56%) noted decrease in the dose of steroids, 14 patients (38.89%) dose remained unchanged. 7 patients (19.44%) required increase in the dose of steroids. 4 patients (11.11%) were not on steroids. For 7 patients we did not have the information on use of steroids. PFS was better for patients treated with chemotherapy + BEV with median PFS of 6.9 months, 95% CI 3.2- 22.3 verses BEV alone with median PFS 3.53 months 95% CI 1.4–5.3, P-value 0.0449. The Cox regression model for PFS to test comparing Bev with chemotherapy vs. Bev alone with the co-variables of sex, age, and ECOG performance status (PS). The model showed that patient with higher ECOG PS were noted to have inferior PFS with a Hazard ratio of 1.92 95% CI 1.09–3.37. P value of 0.2. Patient treated with BEV+ chemo had better PFS with a HR of 6.44 95% CI 1.86–22.28. P value of 0.003. CONCLUSION Retrospective real world study confirms that, patients with recurrent GBM, treatment with BEV is associated with similar PFS as reported in literature. Our study showed similar overall survival from the diagnosis compared to historic control. However the Median OS from Start of BEV was noted to be inferior to what is reported in EORTC EH1.3. Better ECOG performance status is associated with better PFS. Higher number of patients with ECOG 2 and 3 received BEV alone.

Combination therapy based on bortezomib for 102 patients with newly-diagnosed multiple myeloma: a Chinese experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5116-5116
Author(s):  
Jingsong He ◽  
Li Yang ◽  
Xiaoyan Han ◽  
Gaofeng Zheng ◽  
Xiaojian Meng ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Peripheral Neuropathy ◽  
Combination Therapy ◽  
Adverse Events ◽  
Chinese Population ◽  
Median Overall Survival ◽  
Chinese Patients ◽  
Newly Diagnosed ◽  
Significant Difference

Abstract Abstract 5116 Multiple myeloma (MM) is a malignant neoplasm of plasma. The rates of complete remission (CR) or very good partial remission (VGPR) for patients received conventional chemotherapy are still low with median overall survival about 3 years. Here we report our results with combination therapy based on bortezomib in the Chinese population and investigat the efficacy and safety of Bortezomib-based therapies in previously untreated MM patients. Metohds: Between 1st Feb. 2006 and 31st Dec. 2010, 102 consecutive newly-diagnosed patients with symptomatic MM were treated with combination therapies based on bortezomib. Sixty-four patients were male and 38 were female. Median age was 59 years (range 31–86 years). Forty-two patients were stage 3 according to the International Staging System, 36 patients were stage 2 and 24 patients were stage 1. The combinations included dexamethasone (BD group ), dexamethasone plus subsequent thalidomide (BDT group ) and dexamethasone plus cyclophosphamide (BDC group ) or epirubicin (BDA group ) based on bortezomib. Thirty-five patients were in BDT group, 19 in BD group, 32 in BDC group and 16 in BDA. All patients received a median of three cycles of therapy (range 1–5 ). The IMWG criteria was used for response evaluation and toxicities were evluated according to the NCI Common Toxicity Criteria version 3. Results: The efficacy of the triplet combination therapy based on bortezomib including BDT, BCD and BAD were better than BD group, with response rate greater than or equal to partial remission(≥PR) 85.7%, 90.6%, 93.7% and 68.4%, respectively. The efficacy of BDA and BDC group were significantly superior to BD group (P=0.048,0.050). Bortezomib in combination with chemotherapy was highly effective as treatment for symptomatic multiple myeloma, even only after one cycle. The efficacy for patients received one cycle of BDT, BD, BCD and BAD was 65.7%, 42.1%, 65.6% and 62.5%, respectively. Patients treated with BD had suboptimal responses to those received BDT, BCD and BAD treatment and one cycle of BCD was superior to one cycle of BD (P=0.019).The median follow-up time was 17m (1–60m), including 31m (1–60m) for 35 patients in BDT group and 16m (2–29m) for the remaining 67 patients. The median progression-free survival (PFS ) of BDT group was 15m (9.8–20.2m ) while BD group was 12m (8.1–15.8m), BCD group was 13m (5.9–20.1m ), and BAD group was 12m (7.8–16.2m ), without significant difference. The median overall survival (OS ) of BDT group was 35m (13.2–56.8m ) while BD, BCD and BAD groups was not reached yet. There was no significant difference in OS among groups, but BCD and BAD were superior to BD group (P=0.104, 0.142 ). The frequent treatment-emergent adverse events includes hematologic adverse events such as neutropenia, anemia, thrombocytopenia and the non-hematologic adverse events like fatigue, infection, constipation, diarrhea, pleural effusion and ascites, herpes zoster and peripheral neuropathy. Patients treated with BDT were more likely to show peripheral neuropathy than those treated with BD, BCD and BAD (91.4% vs 73.6%, 68.7%, 74.9% ), but there is no statistical significant difference (P = 0.131), Grade 2 or 3 peripheral neuropathy was occurred in 45.7% of BDT group significantly higher than BD, BCD and BAD groups. (21.0%, 15.7% and 18.7%, P = 0.028 ). Other related adverse events in all the groups had no significant difference. Routine anticoagulation or anti-thrombsis were not used. Only 1 patient suffered from DVT/PE but did well with treatment. Conclusions: Our preliminary experience in Chinese patients indicated that combination chemotherapy based on bortezomib is highly effective in newly-diagnosed multiple myeloma and BDC, BDA or BDT regimens may be more superior to BD in Chinese population. There were relative lower rates of DVT/PE in the Chinese patients with MM received combination chemotherapy based on bortezomib. Disclosures: No relevant conflicts of interest to declare.

Phase I/II Study on Cytarabine and Idarubicin Combined with Escalating Doses of Clofarabine in Untreated Patients with Acute Myeloid Leukemia and High Risk for Induction Failure (AMLSG 17-10 CIARA)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4038-4038
Author(s):  
Juergen Krauter ◽  
Walter Fiedler ◽  
Richard F. Schlenk ◽  
Peter Paschka ◽  
Felicitas Thol ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Older Patients ◽  
Research Funding ◽  
Historical Control ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Newly Diagnosed ◽  
Allogeneic Hct ◽  
Induction Failure

Abstract Background: Clofarabine is a second-generation purine nucleoside analogue, which has shown synergistic activity with cytarabine. We determined the maximum tolerated dose (MTD, primary endpoint), safety and efficacy (secondary endpoints) of clofarabine in combination with cytarabine and idarubicin in newly diagnosed acute myeloid leukemia (AML) patients with high-risk for induction failure stratified in two age groups (< 60 years and ≥ 60 years). Methods: In this prospective, open-label, multicenter phase I/II study (EudraCT 2010-021719-18, CIARA trial), newly diagnosed AML patients with high risk of induction failure (NPM1 wildtype, FLT3-ITD negative), who were eligible for intensive chemotherapy, received two induction courses (cytarabine 750 mg/m2 d1-5, idarubicin 7.5 mg/m2 in patients <60 years or 6 mg/m2 in patients ≥60 years d1+3) with increasing doses of clofarabine (20-35 mg/m2 d1-5) following a 3+3 design with extension cohorts. Consolidation consisted of up to 3 courses of high-dose cytarabine or allogeneic hematopoietic cell transplantation (HCT). Results: Forty-two patients with de novo (n=32) or secondary (n=10) AML were included. Median age was 58.5 years (range 28-73, 24 patients < 60 years, 18 patients ≥ 60 years). Intermediate/adverse risk cytogenetics were found in 22 and 12 patients, respectively (karyotype missing in 8 patients). All patients received induction 1, 27 (64%) received induction 2; 4 (10%) patients died during induction courses 1 or 2. Eight patients developed a dose-limiting toxicity (6 patients with grade 3/4 non-hematologic toxicity and 3 patients with grade 4/5 hematologic toxicity) and the MTD was determined at 30 mg/m2 clofarabine for both age cohorts (younger patients: 2 of 6 patients with DLT at 35 mg/m2, no DLT at 30 mg/m2 (n=9); older patients: 4 of 6 patients with DLT at 35 mg/m2 in the extension phase, no DLT at 30 mg/m2 (n=3). The most frequent grade 3-5 non-hematologic adverse events were febrile neutropenia, sepsis, increased liver enzymes, pneumonia, decreased appetite and diarrhea occurring in 55, 24, 21, 21, 10 and 10% of patients. The median time to neutrophils ≥0.5/nl and platelets ≥50/nl after induction 1 was 25 and 24 days, respectively. Sixteen patients (38%) proceeded to allogeneic HCT in first CR and 8 (19%) received at least one course of high-dose cytarabine consolidation. Complete remission (CR) or CR with incomplete recovery (CRi) was achieved in 67%. After a median follow up of 2.2 years the 2-year overall survival (OS) was 56% and the 2-year event-free survival was 38% (median EFS 11.4 months). Compared to a matched historical control of 197 younger AML patients (SHG 0199 trial, Schlenk et al. NEJM 2008), the CR rate was 79% in the 24 younger CIARA patients compared to 66% in the control cohort (P=.18), and 2-year OS was higher for CIARA than for control patients (74% vs 49%, P=.021, Figure A). The allogeneic HCT rate in first CR (CR1) was higher in younger CIARA compared to younger control patients (58% vs 27%, P=.002). The CR rate in older CIARA patients was 50% compared to 36% in a historical control of 191 older patients, who were selected using the same genetic inclusion criteria as for CIARA patients (HD98B trial, Schlenk et al. Haematologica 2009, P=.23). Two-year OS in older patients was similar between CIARA and control patients (33% vs 17%, P=.31, Figure B). The allogeneic HCT rate in CR1 was 11% vs 2% in CIARA vs control patients (P=.029). Conclusion: Clofarabine can be safely administered at 30 mg/m2 in combination with cytarabine and idarubicin in younger and older newly diagnosed AML patients. Allogeneic HCT in CR1 was feasible in a high proportion of younger AML patients and likely contributed to the favorable outcome compared to historical control patients. Figure Overall survival in younger and older AML patients of the CIARA trial compared to historical controls. Figure. Overall survival in younger and older AML patients of the CIARA trial compared to historical controls. Disclosures Krauter: Genzyme: Research Funding. Schlenk:Amgen: Research Funding; Pfizer: Honoraria, Research Funding. Paschka:Novartis: Consultancy; Medupdate GmbH: Honoraria; Bristol-Myers Squibb: Honoraria; Pfizer Pharma GmbH: Honoraria; Celgene: Honoraria; ASTEX Pharmaceuticals: Consultancy. Lübbert:Ratiopharm: Other: Study drug valproic acid; Celgene: Other: Travel Funding; Janssen-Cilag: Other: Travel Funding, Research Funding. Janning:Teva: Honoraria. Becker:BMS: Honoraria; Novartis: Honoraria. Heuser:Tetralogic: Research Funding; Novartis: Consultancy, Research Funding; Celgene: Honoraria; Pfizer: Research Funding; Bayer Pharma AG: Research Funding; BerGenBio: Research Funding; Karyopharm Therapeutics Inc: Research Funding.

scholarly journals Real-World Data for Lenvatinib in Hepatocellular Carcinoma (ELEVATOR): A retrospective multicenter study

Liver Cancer ◽  
2022 ◽  
Author(s):  
Sabrina Welland ◽  
Catherine Leyh ◽  
Fabian Finkelmeier ◽  
André Jefremow ◽  
Kateryna Shmanko ◽  
...  
Keyword(s):  
Overall Survival ◽  
Real World ◽  
Median Overall Survival ◽  
Performance Status ◽  
Progression Free Survival ◽  
Inclusion Criteria ◽  
First Line ◽  
Ecog Performance Status ◽  
Free Survival ◽  
First Line Treatment

Background Lenvatinib is approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinib in Caucasian real-world patients is insufficiently defined. The purpose of this study was to evaluate the efficacy of lenvatinib in a multi-center cohort (ELEVATOR) from Germany and Austria. Methods A retrospective data analysis of 205 patients treated with first-line systemic lenvatinib at 14 different sites was conducted. Overall survival, progression free survival, overall response rate and adverse event rates were assessed and analyzed. Results Patients receiving lenvatinib in the real-world setting reached a median overall survival of 12.8 months, which was comparable to the results reported from the REFLECT study. Median overall survival (mOS) and progression free survival (mPFS) was superior in those patients who met the inclusion criteria of the REFLECT study compared to patients who failed to meet the inclusion criteria (mOS 15.6 vs 10.2 months, HR 0.55, 95% CI 0.38-0.81, p=0.002; mPFS 8.1 vs 4.8 months HR 0.65, 95% CI 0.46-0.91, p=0.0015). For patients with an impaired liver function according to the Albumin-Bilirubin (ALBI) grade, or reduced ECOG performance status ≥2, survival was significantly shorter compared to patients with sustained liver function (ALBI grade 1) and good performance status (ECOG performance status 0), respectively (HR 1.69, 95% CI 1.07-2.66, p=0.023; HR 2.25, 95% CI 1.19-4.23, p=0.012). Additionally, macrovascular invasion (HR 1.55, 95% CI 1.02-2.37, p=0.041) and an AFP ≥200 ng/mL (HR 1.56, 95% CI 1.03-2.34, p=0.034) were confirmed as independent negative prognostic factors in our cohort of patients with advanced HCC. Conclusion Overall, our data confirm the efficacy of lenvatinib as first-line treatment and did not reveal new or unexpected side effects in a large retrospective Caucasian real-world cohort, supporting the use of lenvatinib as meaningful alternative for patients that cannot be treated with IO-based combinations in first-line HCC.

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