Standard Anthracycline-based Regimen Research Articles

Anthracycline-free or short-term regimen as adjuvant chemotherapy for operable breast cancer: A phase III randomized non-inferiority trial

BackgroundDe-escalating anthracycline is gaining popularity for breast cancer patients. We aim to evaluate the non-inferiority of an anthracycline-free or short-term regimen to the standard anthracycline-based regimen for operable patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer. MethodsIt is a prospective, open-label, phase 3, randomized non-inferiority trial from June 1, 2010 to June 1, 2017. Follow-up had been kept until July 2019. This trial was conducted at Fudan University Shanghai Cancer Center. Patients with pT1–3N+ or pT2–3N0 but high-risk (grade II/III, lymphovascular invasion, ≤35 years of age or hormone-receptor negative) HER2-negative operable breast cancer were eligible and stratified by age, pathological tumour stage, pathological node status and hormone-receptor status. Patients were randomized to 6 cycles of docetaxel and cyclophosphamide (TC, n = 524), 3 cycles of cyclophosphamide/epirubicin/fluorouracil followed by 3 cycles of docetaxel (CEF-T, n = 523) or epirubicin and cyclophosphamide for 4 cycles followed by paclitaxel for 12 weeks (EC-P, n = 524) as the intention-to-treat population. Of these patients, 94% completed allocated therapy. Difference in disease-free survival (DFS) compared to EC-P. The prespecified non-inferiority margin was 4.5%, corresponding to the hazard ratio (HR) of 1.44 (one-sided α = 0.05), with an assumed 5-year DFS of 89% for EC-P. FindingsIncluded in the intention-to-treat population were 1571 patients (median [IQR] age, 50 [45–57] years; 92% estrogen receptor [ER]-positive; 59% pN+). Through a median follow-up of 5.5 years, HR for TC versus EC-P was 1.05 (5-year DFS: 85.0% vs. 85.9%; 90% confidence interval [CI]: 0.79–1.39, non-inferior P = 0.048) and for CEF-T versus EC-P, 0.99 (5-year DFS: 85.1% vs. 85.9%; 90% CI: 0.75–1.30, non-inferior P = 0.045). Grade 3 or 4 adverse events for TC included rash (3.9%) and peripheral neuropathy (2.8%) and for CEF-T and EC-P diarrhea and nausea/vomiting were predominant. Results of per-protocol analyses were similar. InterpretationBoth TC and CEF-T are non-inferior adjuvant regimen to EC-P mainly in patients with ER+HER2- breast cancer. TC is a safe regimen that avoids anthracycline-related side effects. FundingThis work was supported by grants from the National Natural Science Foundation of China (Grants 81672600, 81722032, 82072916, and 91959207), the 2018 Shanghai Youth Excellent Academic Leader, the Fudan ZHUOSHI Project, the Municipal Project for Developing Emerging and Frontier Technology in Shanghai Hospitals (grant SHDC12010116), the Cooperation Project of Conquering Major Diseases in the Shanghai Municipality Health System (grant 2013ZYJB0302), the Innovation Team of the Ministry of Education (grant IRT1223), and the Shanghai Key Laboratory of Breast Cancer (grant 12DZ2260100) and the National Cancer Institute (grant P30 CA16058).

Phase 1 First-in-Human Trial of AMV564, a Bivalent Bispecific (2:2) CD33/CD3 T-Cell Engager, in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)

Background: AMV564 is a novel bivalent, bispecific (2x2) CD33/CD3 targeted immunotherapy that binds both CD33 and the invariant CD3e on T-cell receptors with strong avidity, thus creating an immune synapse between CD33-expressing cells and T cells, initiating T-cell directed lysis of CD33 expressing cells, and inducing expansion, differentiation and proliferation of T cells. By design, AMV564 has reduced clearance and therefore has a longer half-life (t1/2) than monovalent, bispecific T-cell engagers. In preclinical investigations using both leukemic cell lines and primary cells from AML patients, AMV564 eliminated myeloid blasts with picomolar potency and broad activity independent of cytogenetic or molecular abnormalities, CD33 expression level, and disease stage, with no nonspecific activation of T cells (Reusch U et al. Clin Cancer Res 2016;22:5829-38). Methods: This is an ongoing Phase 1 study with a 3+3 dose-escalation design (NCT03144245). The primary objectives of this study are to characterize the safety, tolerability, and preliminary anti-leukemic activity of AMV564. Evaluation of pharmacokinetics (PK), cytokine changes, and immunophenotyping are secondary objectives. Key inclusion/exclusion criteria are: adults with relapsed and/or refractory AML after 1-2 prior induction regimens (with a standard anthracycline-based regimen or hypomethylating agent) and no more than 2 prior salvage regimens. AMV564 is administered by continuous intravenous infusion (CIV) for 14 consecutive days for up to 2 induction cycles. AMV564 and cytokine (IL2, IL4, IL6, IL8, IL10, TNF-α, and IFN-γ) concentrations were measured by validated immunoassays. T-cell activation was measured using flow cytometry to quantify T cells expressing CD25, CD38, CD69, or HLA-DR. Results: To date, 19 patients (10 male/9 female) with a median age of 72 years (range 24-84) have been enrolled in 6 dosing cohorts: 0.5, 1.5, 5.0, 15, 50, and 100 mcg/day. Thirteen patients (68%) had secondary AML and/or adverse cytogenetics, including 6 patients (32%) with a p53 mutation. Fifteen patients (79%) had received at least 1 prior salvage regimen and 11 (58%) had received prior intensive chemotherapy, including 6 patients (32%) who had received a high-dose (≥ 1 gm/m2) cytarabine-based regimen. Overall, 18 patients were evaluable for toxicity and response. No dose-limiting toxicity or treatment-related grade ≥ 3 adverse events (AE) were reported. Grade 2 CRS was observed in 1 patient (treated at 50 mcg/day) without a lead-in dose and was managed with drug interruption and 1 dose of tocilizumab. The patient was able to resume dosing and completed the full 14-day scheduled therapy without recurrence of CRS. Subsequent patients treated at 50 mcg/day and above were given a 15 mcg/day lead-in dose for 3 days followed by 11 days at the assigned dose level. The most common grade ≥ 3 treatment-emergent AE has been febrile neutropenia, reported in 39% (7/18) of patients and all considered unrelated to study drug. No patient has died within 30 days of treatment initiation. AMV564 PK was linear with a terminal t1/2 of 2-3 days. Plasma concentrations increased gradually, with times to steady-state concentration of 3-7 days. Marked increases in IL6 (peak concentration, 1.1 ng/mL), IL8 (1.5 ng/mL), and IL10 (0.3 ng/mL) cytokines were observed and increased numbers of activated T-cells were detected post-treatment. Reductions in bone marrow blasts, ranging from 13% to 91%, were observed in 12 of 18 evaluable patients including a partial response after cycle 1 in 1 patient at the 100 mcg/day dose level. Conclusions: AMV564 is well-tolerated and demonstrates anti-leukemic activity through T-cell engagement. AMV564 has a unique PK profile with a gradual increase in drug concentration and thus the potential for controlled T-cell activation. Disclosures Roboz:Daiichi Sankyo: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Aphivena Therapeutics: Consultancy; Cellectis: Research Funding; Argenx: Consultancy; Eisai: Consultancy; Celgene Corporation: Consultancy; Roche/Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Otsuka: Consultancy; Roche/Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Otsuka: Consultancy; AbbVie: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy; AbbVie: Consultancy; Astex Pharmaceuticals: Consultancy; Bayer: Consultancy; Novartis: Consultancy; Sandoz: Consultancy; Novartis: Consultancy; Celltrion: Consultancy; Aphivena Therapeutics: Consultancy; Pfizer: Consultancy; Cellectis: Research Funding; Eisai: Consultancy; Orsenix: Consultancy; Celltrion: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Daiichi Sankyo: Consultancy; Orsenix: Consultancy. Cortes:Novartis: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Arog: Research Funding. Lee:AstraZeneca: Consultancy; Clinipace: Consultancy; Karyopharm Therapeutics Inc: Consultancy; LAM Therapeutics: Research Funding; Amgen: Consultancy. Rettig:Amphivena Therapeutics: Research Funding; Novimmune: Research Funding. Han:Amphivena Therapeutics, Inc: Employment. Guenot:Amphivena Therapeutics, Inc: Employment. Feldman:Amphivena Therapeutics, Inc: Employment.

Phase 1 First-in-Human Trial of AMV564, a Bivalent Bispecific (2x2) CD33/CD3 T-Cell Engager, in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML)

▪Background: AMV564 is a novel bivalent, bispecific (2x2) CD33/CD3 targeted immunotherapy that binds both CD33 and the invariant CD3ε on T-cell receptors with strong avidity, thus creating an immune synapse between CD33-expressing cells and T cells, initiating T-cell directed lysis of CD33 expressing cells, and inducing expansion, differentiation and proliferation of T cells. By design, AMV564 has reduced clearance and therefore has a longer half-life (t1/2) than monovalent, bispecific T-cell engagers. In preclinical investigations using both leukemic cell lines and primary cells from AML patients, AMV564 eliminated myeloid blasts with picomolar potency and broad activity independent of cytogenetic or molecular abnormalities, CD33 expression level, and disease stage, with no nonspecific activation of T cells (Reusch U et al. Clin Cancer Res 2016;22:5829-38).Methods: This is an ongoing Phase 1 study with a 3+3 dose-escalation design (NCT03144245). The primary objectives of this study are to characterize the safety, tolerability, and preliminary anti-leukemic activity of AMV564. Evaluation of pharmacokinetics (PK), cytokine changes, and immunophenotyping are secondary objectives. Key inclusion/exclusion criteria are: adults with relapsed and/or refractory AML after 1-2 prior induction regimens (with a standard anthracycline-based regimen or hypomethylating agent) and no more than 2 prior salvage regimens. AMV564 is administered by continuous intravenous infusion (CIV) for 14 consecutive days for up to 2 induction cycles. AMV564 and cytokine (IL2, IL4, IL6, IL8, IL10, TNF-α, and IFN-γ) concentrations were measured by validated immunoassays. T-cell activation was measured using flow cytometry to quantify T cells expressing CD25, CD38, CD69, or HLA-DR.Results: To date, 19 patients (10 male/9 female) with a median age of 72 years (range 24-84) have been enrolled in 6 dosing cohorts: 0.5, 1.5, 5.0, 15, 50, and 100 mcg/day. Thirteen patients (68%) had secondary AML and/or adverse cytogenetics, including 6 patients (32%) with a p53 mutation. Fifteen patients (79%) had received at least 1 prior salvage regimen and 11 (58%) had received prior intensive chemotherapy, including 6 patients (32%) who had received a high-dose (≥ 1 gm/m2) cytarabine-based regimen. Overall, 18 patients were evaluable for toxicity and response. No dose-limiting toxicity or treatment-related grade ≥ 3 adverse events (AE) were reported. Grade 2 CRS was observed in 1 patient (treated at 50 mcg/day) without a lead-in dose and was managed with drug interruption and 1 dose of tocilizumab. The patient was able to resume dosing and completed the full 14-day scheduled therapy without recurrence of CRS. Subsequent patients treated at 50 mcg/day and above were given a 15 mcg/day lead-in dose for 3 days followed by 11 days at the assigned dose level. The most common grade ≥ 3 treatment-emergent AE has been febrile neutropenia, reported in 39% (7/18) of patients and all considered unrelated to study drug. No patient has died within 30 days of treatment initiation. AMV564 PK was linear with a terminal t1/2 of 2-3 days. Plasma concentrations increased gradually, with times to steady-state concentration of 3-7 days. Marked increases in IL6 (peak concentration, 1.1 ng/mL), IL8 (1.5 ng/mL), and IL10 (0.3 ng/mL) cytokines were observed and increased numbers of activated T-cells were detected post-treatment. Reductions in bone marrow blasts, ranging from 13% to 91%, were observed in 12 of 18 evaluable patients including a partial response after cycle 1 in 1 patient at the 100 mcg/day dose level.Conclusions: AMV564 is well-tolerated and demonstrates anti-leukemic activity through T-cell engagement. AMV564 has a unique PK profile with a gradual increase in drug concentration and thus the potential for controlled T-cell activation. DisclosuresRoboz:Daiichi Sankyo: Consultancy; Argenx: Consultancy; Sandoz: Consultancy; Aphivena Therapeutics: Consultancy; Cellectis: Research Funding; Argenx: Consultancy; Eisai: Consultancy; Celgene Corporation: Consultancy; Roche/Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Otsuka: Consultancy; Roche/Genentech: Consultancy; Jazz Pharmaceuticals: Consultancy; Otsuka: Consultancy; AbbVie: Consultancy; Astex Pharmaceuticals: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy; AbbVie: Consultancy; Astex Pharmaceuticals: Consultancy; Bayer: Consultancy; Novartis: Consultancy; Sandoz: Consultancy; Novartis: Consultancy; Celltrion: Consultancy; Aphivena Therapeutics: Consultancy; Pfizer: Consultancy; Cellectis: Research Funding; Eisai: Consultancy; Orsenix: Consultancy; Celltrion: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Janssen Pharmaceuticals: Consultancy; Daiichi Sankyo: Consultancy; Orsenix: Consultancy. Cortes:Novartis: Consultancy, Research Funding; Astellas Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Arog: Research Funding. Lee:AstraZeneca: Consultancy; Clinipace: Consultancy; Karyopharm Therapeutics Inc: Consultancy; LAM Therapeutics: Research Funding; Amgen: Consultancy. Rettig:Amphivena Therapeutics: Research Funding; Novimmune: Research Funding. Han:Amphivena Therapeutics, Inc: Employment. Guenot:Amphivena Therapeutics, Inc: Employment. Feldman:Amphivena Therapeutics, Inc: Employment.

Standard anthracycline-based vs. docetaxel-capecitabine in early breast cancer: Results from the chemotherapy randomization (R-C) of EORTC 10041/ BIG 3-04 MINDACT phase III trial.

516 Background: The MINDACT trial demonstrated that 46% of breast cancer patients (pts) at high clinical (C) but low genomic (G) risk based on MammaPrint (70-gene signature), might safely forego adjuvant CT (Cardoso NEJM 2016). A second 1:1 randomization (R-C) was optional in all pts for whom CT was decided, between standard anthracycline-based regimens (AT) and experimental docetaxel 75 mg/m² IV + oral capecitabine 825 mg/m² bid x 14 days (DC), q3wks for 6 cycles after surgery. Methods: MINDACT included 6693 pts, of whom 2895 received CT. C-low/G-low pts were allocated to no CT, C-high/G-high to CT and those with discordant G/C results were randomized to use either G or C risk to decide use of CT. Primary endpoint for R-C was disease-free survival (DFS). Secondary endpoints included OS and safety. Statistical hypothesis: HR-0.76 in favour of DC. Results: A total of 1301 pts (45%), of whom 787 (61%) were C-high/G-high, 351 (27%) C-high/G-low, 137 (11%) C-low/G-high, and 26 (2%) C-low/G-low, were randomized to AT or DC. Main reason for not inclusion in R-C was CT given outside the trial. Compliance rates for R-C were 97% overall. At 5-years median follow-up, DFS was not significantly different between AT (649 pts) and DC (652 pts) [HR = 0.83 (0.60- 1.15, p = 0.263], and OS was similar in both arms (HR 0.91, 95% CI, 0.54- 1.53). For the relevant C-high/G-high group, DFS was also not different (5-years DFS 86.1 vs 88.1%; HR 0.83, 95% CI, 0.58-1.21). Of note, number of events is still small (AT: 30; DC: 27). Commonest adverse events in DC were grade 2 hand/foot syndrome (28.5% vs 3.3%), grade 2 diarrhea (13.7% vs 5.8%) and grade 1 peripheral neuropathy (27.1% vs 11.2%). Grade 2 anemia (14.2% vs 5.1%) and grade 4 neutropenia (24.6% vs 20.5%) were higher in AT. Cardiac events occurred in 9 pts overall, including 1 cardiac failure (AT), while 53 pts developed secondary cancers (AT: 32; DC: 21; leukemia: 2 in AT vs. 1 in DC). Four deaths occurred (AT:1 and DC:3) while on therapy. Conclusions: Docetaxel-capecitabine did not improve DFS or OS, compared with standard anthracycline-based CT, including for the C-high/G-high group. Safety profile of both regimens was as expected. Clinical trial information: NCT00433589.

Phase II study of the combination of gemcitabine plus carboplatin as neoadjuvant treatment in locally advanced breast cancer.

652 Background: Although anthracycline-based regimen is standard neoadjuvant chemotherapy for locally advanced breast cancer (LABC), there is some concern about its toxicities such as alopecia and cardiotoxicity. Gemcitabine is another active agent in metastatic breast cancer after failure to anthracycline with less toxicity. The objective of this study is to evaluate efficacy and safety of combination of gemcitabine and carboplatin as induction chemotherapy in LABC. Methods: Patients with histologically confirmed LABC (T3, T4 or N2 and M0) were included. Patients were scheduled to receive 3 cycles of neoadjuvant GC (gemcitabine 1,000 mg/m2 D1, D8 and carboplatin AUC×5) every 21 days. Patients with clinical response underwent surgery and additional 3 cycles of adjuvant GC. Those with clinical stable or progressive disease were taken off study and received standard anthracycline-based regimen. All patients were scheduled for adjuvant radiation and hormonal treatment depending on hormonal status. Primary end point was pathological response rate whereas secondary end points included PFS, OS and toxicity. Results: Between July 2004 and July 2007, 40 patients were enrolled. The median age was 46 years. Twenty-three patients (57.5%) had T4 lesion and 17 (42.5%) had T3. Out of 40 patients, 37 were evaluable for efficacy and 40 for toxicity. Twenty-four out of 37 patients (65%) obtained cPR. Among 23 patients who had clinical response underwent modified radical mastectomy, overall pathological response rate was 51.4% with 1-pCR (2.7%) and 18-pPR (48.6%). All 6 triple-negative patients had pathological response (1-pCR, 5-pPR). At median follow up of 35 months, median PFS and OS were not reached. Two-year OS and PFS were 81.2 % and 60.8 %, respectively. Common grade III and IV adverse effects were neutropenia (67.5%), anemia (45%) and thrombocytopenia (37.5%). Four patients developed grade III hepatitis with complete resolution after discontinuation of GC. No patient developed febrile neutropenia or fatal complications. Conclusions: Combination GC was efficacious, feasible and well-tolerated for LABC in neoadjuvant setting. Triple-negative subgroup seems to have high response to GC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly

Adding cisplatin to an anthracycline-based primary chemotherapy in triple-negative (TN) and non-triple negative (non-TN) T4 breast cancer patients (pts): Long-term outcomes

583 Background: Clinical data demonstrated that standard anthracycline-based chemotherapy may be less beneficial in TN. Conversely, there is extensive preclinical work showing that TN tumors are highly sensitive to platinum agents. Only a few studies compared cisplatin vs non-cisplatin containing regimens among TN or non-TN homogeneous populations. The aim of this study was to evaluate the efficacy in terms of long-term outcomes of adding cisplatin to an anthracycline-based neoadjuvant regimen (cisplatin, C) compared with a standard anthracycline-based (Non-C) regimen in T4 breast cancer according to TN or non-TN status. Methods: We retrospectively analyzed 125 consecutive T4 breast cancer pts available for ER/PR and HER2 status; 98 pts (80%) were non-TN, of whom 63 treated with Non-C and 35 treated with C regimen; 27 pts (20%) were TN, of whom 10 treated with Non-C and 17 treated with C regimen. All pts received CMF, RT and hormone-therapy if indicated as adjuvant setting. None of the HER2 positive pts received peri-operative trastuzumab. Results: At a median follow-up of 101 months (8–217), estimated 10-year DFS and OS in TN pts treated with C were 47% and 59% versus 10% and 30% in pts treated with Non-C. In non-TN pts DFS and OS were 57% and 70% in pts treated with C versus 37% and 49% in pts treated with Non-C. Conclusions: Our data suggest that both TN and non-TN pts derive a better outcomes from the add of cisplatin over a standard anthracycline-based regimen. Of note, the magnitude of the benefit of cisplatin appears greater in the TN group. In order to validate these findings large prospective randomized trials are warranted. [Table: see text] No significant financial relationships to disclose.

Sequential epirubicin-docetaxel-CMF as adjuvant therapy of early breast cancer: Results of the Taxit216 multicenter phase III trial

LBA520 Background: Docetaxel is among the most active drugs for advanced breast cancer and it has recently shown efficacy in the adjuvant setting too. This trial is aimed at comparing the efficacy and tolerability of a sequential approach of a chemotherapy combination regimen containing docetaxel to a standard anthracycline-based regimen as adjuvant therapy in node-positive (N+) early breast cancer. Methods: Between July 1998 and July 2002, 972 N+ early breast cancer patients were randomized to either arm A (E→CMF): Epirubicin (E) 120 mg/m2 iv d1 q21 × 4 cycles followed by Cyclophosphamide 600 mg/m2 iv, Methotrexate 40 mg/m2 iv and Fluorouracil 600 mg/m2 iv (CMF) d1,8 q28 × 4 cycles; or armB (E→T→CMF) in which Docetaxel 100 mg/m2 iv (T) d1 q21 × 4 cycles was administered after the 4th cycle of E and before the 1st cycle of CMF. Treatment allocation was performed by a computer program using a dynamic balancing algorithm. Balancing factors were: center, lymph node involvement (1 to 3, 4 to 9, >10), estrogen receptor status (negative/positive/unknown), menopausal status (pre/post). During chemotherapy pts were subjected to physical examination and blood chemistry tests every 3 wks, hematology was repeated weekly. At the completion of treatment pts were followed up every 3 months for the first 2 years, every 6 months for years 3–5 and every 12 months for years 6–10. Primary endpoint was disease free survival (DFS) and secondary endpoints were tolerability and overall survival (OS). The study was designed to detect a hazard ratio of 0.70, assuming an α of 0.05 (two sided), a power of 0.80 and an expected DFS in Arm A of 0.65 at 5 years. This required 480 pts per Arm and 250 events. Results: As of March 27th 2006, 486 pts were enrolled in arm A and 486 in arm B, 252 primary events were recorded and the median follow up was 53 months. DFS at 5 years was 0.67 in arm A vs 0.74 in arm B with an estimated Hazard Ratio (HR) of 0.80 (95% CI: 0.62–1.03, p = 0.079). After adjustement by predefined balancing factors (ER, Nodal and menopausal status) the HR was 0.78 (95% CIs: 0.61–1.00; p = 0.05). As for OS, 117 deaths were observed with HR of 0.74 (95% CIs: 0.51–1.07, p = 0.10). Conclusions: Sequential E→T→CMF yields a borderline significant improvement of DFS. Follow up update is still ongoing. [Table: see text]

Non-anthracycline based remission induction therapy for newly diagnosed patients with acute myeloid leukemia aged 60 or older

We assessed remission rates and toxicity in 24 consecutive elderly (age ≥ 60) patients with untreated Acute myeloid leukemia (AML) who received the anthracycline-free combination of fludarabine, cytosine arabinoside and G-CSF (FLAG) as initial induction chemotherapy at our center. CR was achieved following one cycle of FLAG in 14 patients (58%). Another four patients cleared blasts from their bone marrow by day 30 without complete platelet recovery. Three patients died from infections prior to neutrophil recovery (12%). No other grade 3/4 toxicities and no clinically significant mucositis were seen. No significant association was found between age, WBC and cytogenetic risk group with likelihood of achieving CR. Fifteen patients proceeded to consolidation therapy and seven patients received a stem cell transplant (six autologous, one allogeneic). Primary induction with FLAG in elderly AML patients achieves a high remission rate without prohibitive mucosal or cardiac toxicity and may thus be considered as an alternative to standard anthracycline-based regimens in this setting.