Low Dose Ara-C Versus Hydroxyurea with or without Retinoid in Older Patients Not Considered Fit for Intensive Chemotherapy: The UK NCRI AML14 Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 872-872 ◽  
Author(s):  
Alan K. Burnett ◽  
Donald Milligan ◽  
Archie G. Prentice ◽  
Anthony H. Goldstone ◽  
Mary F. McMullin ◽  
...  
Keyword(s):  
Older Patients ◽  
Low Dose ◽  
Significant Proportion ◽  
Standard Of Care ◽  
Hazard Ratio ◽  
Intensive Chemotherapy ◽  
Adequate Treatment ◽  
And Performance ◽  
The Uk ◽  
Care Requirements

Abstract There is no adequate treatment for older patients with AML who are not considered fit for intensive chemotherapy who comprise a significant proportion of the AML population. As part of the ongoing NCRI (formerly MRC) AML14 Trial in patients over 60 years patients were randomised to Low Dose Ara-C (20mg bd for 10 days every 4–6 weeks) versus Hydroxycarbamide (Hydroxyurea). Because of preclinical studies showing sensitization to Ara-C, patients were in addition randomised to receive All-transretinoic acid or not (45mgs/m2 for 60 days). Two hundred and four patients entered; 129 had a WHO score of <2; 155 patients were >65 yrs; 108 had do novo, 53 secondary disease and 28 had high risk MDS (blasts >10%). One hundred and ninety-nine patients entered the HU vs LD-Ara-C randomisation and 204 entered the ATRA randomisation. The arms were balanced with respect to age; sex; disease type; WBC and performance score. Complete remission was seen in 1 of 92 (1%) patients in the HU arm and 15 of 94 (17%) in the LD Ara-C arm (P=0003). Overall survival was considerably improved (hazard ratio 0.61, 95% Cl 0.45 to 0.82, p=0.001). This improvement in outcome was not obtained at the expense of less well tolerated treatment: toxicity and supportive care requirements were similar between the two groups. However, there were no significant differences in outcome between patients given ATRA or not overall or within the treatment arms, although numbers were too small to rule out moderate benefits or disbenefits of treatment (hazard ratio for OS 0.97, 95% Cl 0.73 to 1.28, p=0.8). We conclude that LD-Ara-C in the schedule chosen could be adopted as a standard of care for older patients not fit for intensive chemotherapy but the outcome remains poor. Future strategies could combine Low Dose Ara-C with novel agents. This trial received a research grant from the UK Leukaemia Research Fund.

Low Dose Ara-C Versus Low Dose Ara-C and Arsenic Trioxide: the UK NCRI AML16 “Pick a Winner” Comparison.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 486-486
Author(s):  
Nigel H. Russell ◽  
Robert K Hills ◽  
Ann E. Hunter ◽  
Donald Milligan ◽  
William J. Kell ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Older Patients ◽  
Low Dose ◽  
Remission Rate ◽  
Randomised Trial ◽  
Age Distribution ◽  
Significant Proportion ◽  
The Uk

Abstract Abstract 486 A significant proportion of older patients with AML are not treated with conventional intensive chemotherapy [1] because they are unfit or not considered likely to benefit from an intensive treatment approach. Their outcomes are poor. Such patients have typically been treated with low-dose Ara-C (LDAC) or best supportive care (BSC) with hydroxyurea, and unrandomised studies of new agents have been used in this population. A recent randomised trial has shown that LDAC is superior to BSC in these patients [2]. Randomised trials are underway to assess the value of other novel treatments compared to LDAC. In an unrandomised phase 2 trial in 64 patients, Roboz et al found encouraging results using the combination of Arsenic Trioxide and LDAC. [3]. The UK NCRI AML16 trial is a programme of development which aims to test novel agents or combinations in untreated older patients with AML or high risk MDS (marrow blasts >10%) following a “pick a winner” design. The intention is to identify a “winner” which will produce a remission rate in excess of 30%, compared with 15-20% with LDAC. Using LDAC as the standard arm,the design allows unpromising treatments to be identified early (typically after 50 patients per arm), so that only those arms which show promise will continue to a trial with OS and DFS as endpoints. We report our experience of LD Ara-C (20mg bd days 1-10 for 4 courses) versus LDAC combined with Arsenic Trioxide (ATO, 0.25 mg/kg d1-5, d9, d11 for 4 courses at 6-8 week intervals). Patient Details: Between December 2006 and until its conclusion in May 2009, 166 patients were randomised, 84 to LDAC plus ATO, 82 to LDAC. The median age was 74 years; 80% of patients were aged over 70 years, 62% were male. There were no differences between the treatment arms with respect to age distribution, gender, performance status, de novo/secondary AML, high risk MDS, presenting WBC or cytogenetic risk group. Follow-up is complete to 1st January 2009, with median follow up for survivors of 8 months (range 0.1-17), at which point 122 patients had been recruited, and there were a total of 60 deaths (LDAC n=25; LDAC+ ATO, n=35). CR status is known on 113 patients. Overall, 24 patients have entered CR/CRi (LDAC n=13, LDAC+ATO n=11) with 8 relapses (2 vs 6; 1 vs 3 patients have died following relapse). The causes of death (60) were:- The DMEC recommended closure of the LDAC + ATO arm of the trial because follow-up data on the first 50 patients per arm showed that ATO had failed to provide the 2.5% improvement in CR/CRi required for continued recruitment and that the required improvement in remission was unlikely with LDAC + ATO. Conclusions: While ATO has a definite role in treating patients with APL, and may be of benefit in combination with other drugs in AML, the combination of LDAC + ATO in this patient population was not beneficial. [1] Juliusson G et al. Blood 2009; 113: 4179—4187 [2] Burnett et al. Cancer 2007 109: 1114—1124 [3] Roboz Gail J et al. Cancer 2008;113(9):2504—11. Disclosures: Off Label Use: Arsenic Trioxide is not licensed in this indication.

The Addition of Gemtuzumab Ozogamicin to Low Dose Ara-C Improves Remission Rates but Not Survival: Results of the UK LRF AML14 and NCRI AML16 “Pick a Winner” Comparison

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 18-18 ◽  
Author(s):  
Alan Burnett ◽  
Robert Hills ◽  
Ann Elizabeth Hunter ◽  
Donald Milligan ◽  
William J. Kell ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Older Patients ◽  
Low Dose ◽  
Remission Rate ◽  
Significant Proportion ◽  
Gemtuzumab Ozogamicin ◽  
Fixed Dose ◽  
The Uk

Abstract Abstract 18 In a significant proportion of older patients with AML intensive chemotherapy is not considered a viable option[1]. Such patients may receive low-dose Ara-C (LDAC), best supportive care (BSC) with hydroxyurea or an experimental agent but outcomes are poor. We have shown that LDAC is superior to BSC [2], but only in patients who enter CR (fewer than 20%).[2]. There is therefore scope to improve outcomes in these patients, and a number of possible treatments have been evaluated in the randomised UK NCRI AML16 trial, one of which is gemtuzumab ozogamicin (GO), which we have shown to benefit the majority of younger patients when given in conjunction with standard chemotherapy[3]. In AML16 novel agents or combinations are tested in untreated older patients with AML or high risk MDS (marrow blasts >10%) using a “pick a winner” design. The design allows unpromising treatments to be identified early (typically after 50 or 100 patients per arm): only those arms which show promise will continue to a trial with OS and DFS as endpoints. The aim is to at least double the remission rate from 15% to 30%, and thus improve overall survival. We now report the results of LD Ara-C (20mg bd days 1–10 for 4 courses) versus LDAC combined with GO (at a fixed dose of 5mg on day 1 of each course for 4 courses at 6–8 week intervals). Patient Details: The comparison opened as part of the UK LRF AML14 trial and was carried forward to AML16 unchanged. Between June 2004 and June 2010, 495 patients were randomised, 249 to LDAC plus ATO, 246 to LDAC. The median age was 75 years (range 54–90); 83% of patients were aged over 70 years, and 61% were male. To be eligible patients’ LFTs had to be less than twice ULN. Treatment arms were balanced for age, gender, performance status, de novo/secondary AML/high risk MDS, presenting WBC and cytogenetic risk group. Follow-up is complete to 1st January 2010, with median follow up of 21 months. Survival and remission data is available on 412, 404 patients respectively. Treatment Results: The trial passed through both stopping hurdles based on CR/CRi rates and therefore continued to full accrual, with overall survival as primary outcome measure. The table shows the distribution of outcomes: there was no heterogeneity by recruitment period (AML14 vs AML16). The causes of death (316) were:- There were no significant interactions between treatment and any of the baseline variables on either remission or survival outcomes. Likewise there were no major toxicity implications, although resource usage tended to be higher in patients given GO. Discussion: While the addition of GO significantly improves CR rate, achieving the 30% response originally sought, this does not translate into survival. This is predominantly due to an increase in relapse, indicating that if GO is to have a role in this setting, it will require effective treatment to maintain remission. [1] Juliusson G et al. Blood 2009; 113: 4179 – 4187 [2] Burnett et al. Cancer 2007 109: 1114–1124 [3] Burnett et al. JCO 2010 to appear. Disclosures: Off Label Use: Mylotarg (gemtuzumab ozogamicin).

Results of omacetaxine plus low-dose cytarabine (LD-araC) in older patients with acute myeloid leukemia (AML).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7068-7068
Author(s):  
Tapan M. Kadia ◽  
Naval Guastad Daver ◽  
Farhad Ravandi ◽  
Elias Jabbour ◽  
Naveen Pemmaraju ◽  
...  
Keyword(s):  
Older Patients ◽  
Performance Status ◽  
Intensive Chemotherapy ◽  
Eligibility Criteria ◽  
Normal Organ ◽  
Low Intensity ◽  
Resistant Disease ◽  
Poor Tolerance ◽  
And Performance

7068 Background: Older patients with AML have poor tolerance to intensive chemotherapy and poor prognosis. Omacetaxine is active in AML and is part of standard combination chemotherapy in China under the name of homoharringtonine. Methods: The aim of the study was to evaluate the efficacy of low intensity therapy with omacetaxine and LD-ara C in newly diagnosed older patients (>/= 60 years) with AML or myelodysplastic syndrome (MDS). Older patients with AML not fit or who refuse intensive chemotherapy were eligible. Normal organ functions and performance status </= 2 were required. Other eligibility criteria were standard. Induction therapy consisted of omacetaxine 1.25 mg/m2 subcutaneously twice daily for 3 days and ara-C 20 mg subcutaneously twice daily for 7 days. Maintenance therapy was with the same induction schedule, repeated every 4-6 weeks for up to 2 years. Dose adjustments for prolonged myelosupression or severe non-hematologic toxicities were made by reducing the number of days of omacetaxine (-1 day by level) and cytarabine (-1 to 2 days by level). Results: 30 patients have been treated, with a median age of 71 years (range 64-81); 60% were age 70 years or older. AML post MDS in 20%; chromosome 5 and 7 abnormalities were present in 23%. Overall, 9 patients achieved CR (30%), 5 had CRp (17%) and 1 had PR (3%), for an overall response rate of 50%. Induction mortality was noted in 4 (Day 5, 27, 27, and 70 from start of therapy; 13%); resistant disease in 8 (27%); too early in 4 (13%). With the median follow-up time of 10 months the median survival is 9.3 months and the estimated 1-year survival rate 42%. No serious drug related adverse effects were observed with the combination. Conclusions: Low-intensity therapy with omacetaxine + LD-ara C shows promising activity and is safe in older patients with AML not fit for intensive chemotherapy. Clinical trial information: NCT01272245.

scholarly journals Randomised evaluation of quizartinib and low-dose ara-C vs low-dose ara-C in older acute myeloid leukemia patients

2021 ◽  
Author(s):  
Mike Dennis ◽  
Ian Thomas ◽  
Cono Ariti ◽  
Laura Upton ◽  
Alan K Burnett ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Intensive Chemotherapy ◽  
Wild Type ◽  
Flt3 Inhibitor ◽  
Acute Myeloid

Survival for older patients with acute myeloid leukaemia (AML) unsuitable for intensive chemotherapy is unsatisfactory. Standard non intensive therapies have low response rates and only extend life by a few months. Quizartinib is an oral Fms-like tyrosine kinase 3 (FLT3) inhibitor with reported activity in wild type patients. As part of the AML LI trial we undertook a randomised evaluation of low dose ara-C (LDAC) with or without quizartinib in patients not fit for intensive chemotherapy. Overall, survival was not improved (202 patients), but in the 27 FLT3-ITD patients the addition of quizartinib to LDAC improved response (p=0.05) with CR/CRi for quizartinib + LDAC in 5/13 (38%) v 0/14 (0%) in patients receiving LDAC alone. Overall survival (OS) in these FLT3-ITD positive patients was also significantly improved at 2 years for quizartinib + LDAC; hazard ratio 0.36 (95% confidence intervals 0.16, 0.85), (p=0.04). Median OS was 13.7 months compared to 4.2 months with LDAC alone. This is the first report of a FLT3 targeted therapy added to standard non-intensive chemotherapy that has improved survival in this population. Quizartinib merits consideration for future triplet based treatment approaches. (Clinical trial numbers: ISRCTN No: ISRCTN40571019 EUDRACT Number: 2011-000749-19).

A Phase 2 Evaluation of Single Agent Clofarabine as First Line Treatment for Older Patients with AML Who Are Not Considered Fit for Intensive Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 869-869 ◽  
Author(s):  
Alan K. Burnett ◽  
Nigel Russell ◽  
Jonathan W. Kell ◽  
Donald Milligan ◽  
Dominic Culligan
Keyword(s):  
Complete Remission ◽  
Older Patients ◽  
Liver Toxicity ◽  
Single Agent ◽  
Randomised Trial ◽  
Significant Proportion ◽  
Intensive Chemotherapy ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Abstract Patients over 70 years represent a significant proportion of patients with AML. They respond poorly to intensive chemotherapy. Although 50% of patients can achieve CR, only 8% are alive at 2 years (MRC Database). In addition significant numbers of these patients either do not wish to undergo, or are not considered fit for intensive chemotherapy. This represents a significant unmet medical need. Nucleoside analogues (Ara-C) provide an active group of agents in AML, Fludarabine however is ineffective at tolerable doses. Clofarabine has been modified by introducing a Fluorine in the 2′ position which confers reduced susceptibility to cleavage of the glycosidic linkage and also reduced toxicity caused by halogenated nucleobases. As such the drug has potential use as an oral formulation. Previous clinical and in vitro studies have established a dose schedule at 40mg/m2 days 1–5. This is associated with CRs in relapse/refractory AML, but with grade ¾ liver toxicity in 25% of patients. Because of these characteristics we undertook a non-randomised study using a dose of 30mg/m2 days 1-5 IV, which could be repeated for up to 4 courses at a minimum of 28 days apart. The target patient group were patients >70 years, or patients 60–70 with a cardiac history, who were not considered fit for conventional chemotherapy. Twenty-eight patients entered the study: 16 males, 12 females of a median age 71 years (range 60 – 79). The FAB distribution was, M0=1;M1=9; M2=8; M4=2; M5=4; M6=3; Unknown=1. The cytogenetic risk group (MRC criteria) were 26 standard and 2 unfavourable risk. All patients received course 1. Five patients died before response could be assessed from causes which were not thought to be associated with the drug. One patient is too early to assess response. Five did not enter complete remission although there was a reduction in bm blasts from 58 to 18%, 55 to 20% and 30 to 15% in 3 cases. Sixteen patients (59%) achieved complete remission after course 1. Grade 3 toxicity was seen in 3 patients, but this recovered in all cases in a few days. Patients who did not enter CR did not show haematological recovery after course 1 and were considered treatment failures. Of the 16 patients who entered CR, haematological recovery to ANC 1.0 x 109/l took 28 days (range 21–42) Platelets to 50x109/l took 25 days (range 21–38). Conclusions: Clofarabine is an active agent when used alone as first line treatment. It is well tolerated but is associated with cytopenia of an average 28 days. At the dose chosen for this study grade ¾ liver toxicity was uncommon. The drug is a candidate for evaluation in a randomised trial and/or in combination schedules, and lower doses should be explored in older patients. This study was partially supported by an unrestricted grant from Bioenvison Inc.

Low Dose Ara-C Versus Low Dose Ara-C and Tipifarnib: Result of the UK NCRI AML16 “Pick a Winner” Comparison

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2962-2962 ◽  
Author(s):  
Alan K. Burnett ◽  
Robert Hills ◽  
Donald Milligan ◽  
William J. Kell ◽  
Keith Wheatley ◽  
...  
Keyword(s):  
High Risk ◽  
Older Patients ◽  
Low Dose ◽  
De Novo ◽  
Remission Rate ◽  
Performance Status ◽  
Randomised Trial ◽  
Age Distribution ◽  
Best Supportive Care ◽  
The Uk

Abstract Novel treatments are needed for older patients with AML who are not thought likely to benefit from standard chemotherapy. A recent randomised trial demonstrated that Low Dose Ara-C (LD Ara-C) was superior to best supportive care (BSC) (Burnett et al Cancer2007: 109: 1114–1124). The Farnesyl Transferase inhibitor, Tipifarnib, has produced encouraging responses in this patient group (Lancet 109; 1387–1394) although in a subsequent randomised comparison vs BSC it was not superior (Haroussea et al Blood1997:110,135a) The UK NCRI AML16 trial aims to test novel agents or combinations in untreated older patients with AML or high risk MDS (marrow blasts &gt;10%) following a “pick a winner” design. The intention is to randomise up to 50 patients per arm with the expectation that a “winner” will achieve a remission rate in excess of 30%, compared with 15–20% with LD Ara-C. If that is achieved randomisation will continue with OS and DFS as endpoints. We report our experience of LD Ara-C (20mg bd days 1–10 for 4 courses versus LD Ara-C combined with Tipifarnib (300mg bd days 1–21) for 4 courses at 6–8 week intervals. Patient Details: Sixty-five patients were randomised between December 2006 and October 2007. The median age was 74.4 years with 82% of patients over 70 years. There were no differences between the treatment arms with respect to age distribution, gender, performance status, de novo/secondary AML, high risk MDS presenting WBC or cytogenetic risk group. Because of concerns about excess deaths in the Tipifarnib arm and therefore the low probability that LD Ara-C + Tipifarnib would be superior to LD Ara-C alone, the DMEC recommended premature closure of the Tipifarnib arm. Conclusions: While other agents combined with Tipifarnib may continue to show promise, the combination with LD-Ara-C in this patient population was not beneficial.

scholarly journals Autologous stem cell transplantation is safe and effective for fit older myeloma patients: exploratory results from the Myeloma XI trial

Haematologica ◽  
2020 ◽  
pp. 0-0
Author(s):  
Charlotte Pawlyn ◽  
David Cairns ◽  
Tom Menzies ◽  
John Jones ◽  
Matthew Jenner ◽  
...  
Keyword(s):  
Stem Cell ◽  
Induction Therapy ◽  
Older Patients ◽  
Controlled Trial ◽  
Standard Of Care ◽  
Autologous Stem Cell Transplant ◽  
Phase Iii ◽  
Cell Transplant ◽  
Randomised Controlled ◽  
The Uk

Autologous stem cell transplant (ASCT) remains standard of care for consolidation after induction therapy for eligible newly diagnosed myeloma patients. In recent clinical trials comparing ASCT to delayed ASCT, patients aged over 65 were excluded. In real-world practice stem cell transplants are not restricted to those aged under 65 and clinicians decide on transplant eligibility based on patient fitness rather than a strict age cut off. Data from the UK NCRI Myeloma XI trial, a large phase III randomised controlled trial with pathways for transplant-eligible (TE) and ineligible (TNE) patients, was used in an exploratory analysis to examine the efficacy and toxicity of ASCT in older patients including analysis using an agematched population to compare outcomes for patients receiving similar induction therapy with or without ASCT. Older patients within the TE pathway were less likely to undergo stem cell harvest at the end of induction than younger patients and of those patients undergoing ASCT there was a reduction in PFS associated with increasing age. ASCT in older patients was well tolerated with no difference in morbidity or mortality between patients aged

Comparative Effectiveness of Glasdegib or Venetoclax in Combination with Low-Dose Cytarabine Using Simulated Treatment Comparisons

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 17-18
Author(s):  
Gabriel Tremblay ◽  
Patrick Daniele ◽  
Mike Dolph ◽  
Timothy J. Bell ◽  
Geoffrey Chan ◽  
...  
Keyword(s):  
Comparative Effectiveness ◽  
Older Patients ◽  
Low Dose ◽  
Patient Characteristics ◽  
Intensive Chemotherapy ◽  
Publicly Traded ◽  
Secondary Aml ◽  
Treatment Comparisons ◽  
Low Dose Cytarabine

Background: Older patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy have a poor prognosis, further encumbered by the lack of well-tolerated standard therapies. Combinations of glasdegib with low-dose cytarabine (GLAS+LDAC) and venetoclax with LDAC (VEN+LDAC) are non-intensive chemotherapy (NIC) options recommended by the National Cancer Comprehensive Network Guidelines. As these regimens have not been compared in a head-to-head trial, indirect treatment comparisons (ITC) are of clinical relevance to assess their comparative effectiveness. Hazard ratios (HR) for overall survival (OS) estimate relative survival valued equally throughout follow-up, unlike landmark measures of OS, which may overvalue or undervalue survival at a single time point. This simulated treatment comparison (STC) study compared OS HRs between GLAS+LDAC and VEN+LDAC among older patients with AML unfit for IC. Methods: This analysis utilized individual AML patient data (IPD) from the BRIGHT AML 1003 GLAS+LDAC trial (N=116) and published summary data extracted from the Phase III VEN+LDAC trial (N=211). STC was used following Decision Support Unit Guidelines from the National Institute for Health and Care Excellence. Parametric time-to-event regression models for OS were generated using the GLAS+LDAC IPD; optimal exponential models are presented based on fit statistics. OS HRs were estimated after adjusting for baseline patient characteristics of the GLAS+LDAC trial to match the VEN+LDAC trial. Full and backwards stepwise models (retention p-value &lt;0.2) were constructed considering all mutually available patient covariates including age, sex, de novo vs secondary AML, bone marrow blast &gt;50%, Eastern Cooperative Oncology Group performance status, and cytogenetic risk. OS HRs were indirectly compared by ITC (unadjusted for covariates) and STC (adjusted) with 95% confidence intervals (CIs). ITC and STC used post-hoc analysis results for VEN+LDAC; a sensitivity analysis of pre-specified analysis results for VEN+LDAC was conducted. Results: Overlapping Kaplan Meier (KM) curves for GLAS+LDAC and VEN+LDAC (Figure 1A) suggest that survival probability was similar throughout follow-up. Comparisons of crude survival rates, however, do not account for differences in patient characteristics between studies. Patients in the GLAS+LDAC trial were more likely to be male, have secondary AML, and had worse cytogenetic risk profiles than the VEN+LDAC trial. Unadjusted ITC estimated that GLAS+LDAC numerically (but not statistically) favored over VEN+LDAC, with a 34% (HR: 0.66; 95%CI: 0.38, 1.15) reduction in mortality (Figure 1B). Similarly, following STC with full covariate adjustment, the estimated comparative advantage of GLAS+LDAC over VEN+LDAC widened to 44% (HR: 0.56; 95%CI: 0.24, 1.31). Results of the sensitivity analyses were consistent with these findings. Conclusion: This study indirectly compared OS HRs of GLAS+LDAC and VEN+LDAC in older patients with AML unfit for intensive chemotherapy. In the absence of a head-to-head trial, a well-conducted STC provides the best adjusted estimate of comparative effectiveness between treatments. Unadjusted ITC and adjusted STC revealed that the OS HR numerically favored GLAS+LDAC over VEN+LDAC, albeit not significantly. These findings suggest that the decision between these two recommended NIC regimens may not be based solely on differences in survival outcomes. Rather, the safety profile, the burden of administration, and patient preference will need to be factored into treatment decisions. Figure 1. KM and ITC/STC Results Figure 1 Disclosures Tremblay: Pfizer Inc.: Consultancy; Purple Squirrel Economics: Current Employment. Daniele:Purple Squirrel Economics: Current Employment; Pfizer Inc: Consultancy. Dolph:Purple Squirrel Economics: Current Employment; Pfizer Inc: Consultancy. Bell:Pfizer: Current Employment, Current equity holder in publicly-traded company. Chan:Pfizer Inc.: Current Employment. Brown:Pfizer: Current Employment, Current equity holder in publicly-traded company. Cappelleri:Pfizer Inc.: Current Employment.

scholarly journals A novel treatment regimen of granulocyte colony-stimulating factor combined with ultra-low-dose decitabine and low-dose cytarabine in older patients with acute myeloid leukemia and myelodysplastic syndromes

2021 ◽  
Vol 12 ◽  
pp. 204062072110093
Author(s):  
Huan Zhu ◽  
Bin Yang ◽  
Jia Liu ◽  
Biao Wang ◽  
Yicun Wu ◽  
...  
Keyword(s):  
Treatment Regimen ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Response Rate ◽  
Intensive Chemotherapy ◽  
Granulocyte Colony Stimulating Factor ◽  
Novel Treatment ◽  
Stimulating Factor ◽  
Low Dose Cytarabine

Background: Older patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) unfit for intensive chemotherapy are emergent for suitable treatment strategies. Hypomethylating agents and low-dose cytarabine have generated relevant benefits in the hematological malignancies over recent decades. We evaluated the efficacy and safety of the novel treatment regimen consisting of ultra-low-dose decitabine and low-dose cytarabine, with granulocyte colony-stimulating factor (G-CSF) in this population of patients. Methods and materials: Patients aged more than 60 years with newly diagnosed AML/MDS were enrolled to receive therapy combined of 300 µg subcutaneously per day for priming, decitabine 5.15–7.62 mg/m2/d intravenously and cytarabine 15 mg/m2/d twice a day subcutaneously and G-CSF for consecutive 10 days every 28 days. The study enrolled 28 patients unfit for standard intensive chemotherapy. The median age of patients was 68 years (range 60–83 years) and 20 (71.4%) patients harbored AML. The primary outcome was to evaluate overall response rate. Results: Overall, this novel ultra-low-dose treatment regimen was well tolerated, with 0% of both 4- and 8-week mortality occurrence. Objective response rate (CR + CRi + PR in AML and CR + mCR + PR in MDS) was 57.1% after the first treatment course. Responses of hematologic improvement (HI) aspect were achieved in 18 of 28 (64.3%) patients, 11 (39.3%), 12 (42.9%), and eight patients (28.6%) achieved HI-E, HI-P, HI-N, respectively. Conclusions: Untreated elderly with AML/MDS were well tolerated and benefited from this novel ultra-low-dose treatment regimen.

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