Improved overall survival with Gemtuzumab Ozogamicin (GO) compared with best supportive care (BSC) in elderly patients with untreated acute myeloid leukemia (AML) not considered fit for intensive chemotherapy: final results from the randomized phase III study (AML-19) of the EORTC and gimema leukemia groups

peer reviewe

Survival improvement over time of 960 s-AML patients included in 13 EORTC-GIMEMA-HOVON trials

We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A; n = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B; n = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C; n = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively. Among patients ≤60 years and classified in the cohorts A or B (n = 367), the 5-year overall survival (OS) rate was 28%. There was a systematic improvement in the 5-year OS rate over three time periods (p 60 years of age (n = 502), the OS was dismal, and there was no improvement over time

Idarubicin and cytarabine in combination with gemtuzumab ozogamicin (IAGO) for untreated patients with high-risk MDS or AML evolved from MDS: a phase II study from the EORTC and GIMEMA Leukemia Groups (protocol 06013)

The primary objective of this trial was to assess the feasibility, toxicity profile, and antitumor activity of gemtuzumab ozogamicin (GO) combined with a chemotherapy remission-induction regimen in adults with untreated high-risk myelodysplastic syndrome (HR-MDS) or secondary acute myeloid leukemia (sAML). In this phase II trial, 30 patients with median age of 58 years received 1 day of GO as a 1-h infusion at the dose level of 5 mg/m² on day 7 of the remission-induction course further consisting of a continuous infusion of cytarabine 100 mg/m²/day for 10 days and idarubicin 12 mg/m²/day on days 1, 3, and 5. A consolidation course, consisting of intermediate-dose cytarabine (A) and idarubicin (I) followed by hematopoietic stem cell transplantation (HSCT) was planned for patients in complete remission (CR). The primary endpoints were response rate (CR/CRi) and severe toxicity rate. The secondary endpoint(s) were survival and progression-free survival (PFS) from start of treatment. Thirteen patients (43 %) achieved CR (eight patients) or CR with incomplete hematopoietic recovery (CRi) (five patients). In patients who achieved CR or CRi, the median timeto recovery of neutrophils to 0.5x109/1 and of platelets to >50x109/1 was 29 and 30 days, respectively. Grade 3 to 4 severe toxicities occurred in nine patients. The most prominent was liver toxicity, as shown by elevated bilirubin levels in 16 patients and one case of nonfatal veno-occlusive disease (VOD). All 13 patients with CR/CRi received consolidation therapy, which was followed by allogeneic HSCT in five patients and autologous HSCT in three patients. According to the statistical design of the study, the idarubicin and cytarabine in combination with gemtuzumab ozogamicin (IAGO) regimen did not show sufficient activity to warrant further exploration of this regimen in adult patients with HR-MDS or sAML

Low-dose clofarabine in combination with a standard remission induction in patients aged 18-60 years with previously untreated intermediate and bad-risk acute myeloid leukemia or high-risk myelodysplastic syndrome: Combined phase I/II results of the EORTC/GIMEMA AML-14A trial

Contains fulltext : 169738.pdf (publisher's version ) (Open Access

Survival Improvement over Time of 960 s-AML Patients Included in 13 EORTC-GIMEMA-HOVON Trials

We report the outcomes of secondary acute myeloid leukemia (s-AML) patients included in one of 13 European Organisation for Research and Treatment of Cancer (EORTC) collaborative AML trials using intensive remission-induction chemotherapy. Among 8858 patients treated between May 1986 and January 2008, 960 were identified as having s-AML, either after MDS (cohort A; n = 508), occurring after primary solid tumors or hematologic malignancies other than MDS (cohort B; n = 361), or after non-malignant conditions or with a history of toxic exposure (cohort C; n = 91). Median age was 64 years, 60 years and 61 years in cohort A, B and C, respectively. Among patients ≤60 years and classified in the cohorts A or B (n = 367), the 5-year overall survival (OS) rate was 28%. There was a systematic improvement in the 5-year OS rate over three time periods (p < 0.001): 7.7% (95% CI: 1.3–21.7%) for patients treated before 1990 (period 1: n = 26), 23.3% (95% CI: 17.1–30.0%) for those treated between 1990 and 2000 (period 2: n = 188) and 36.5% (95% CI: 28.7–44.3%) for those treated in 2000 or later (period 3: n = 153). In multivariate analysis, male gender (HR = 1.39; p = 0.01), WBC ≥ 25 × 109/L (HR = 2.00; p < 0.0001), age 46-60 years (HR = 1.65; p < 0.001) and poor-risk cytogenetics (HR = 2.17; p < 0.0001) were independently associated with shorter OS, while being treated during period 2 (HR = 0.50, p = 0.003) or period 3 (HR = 0.43; p = 0.0008). Having received high-dose cytarabine (HD-AraC) (n = 48) in the induction chemotherapy (HR = 0.54, p = 0.012) was associated with a longer OS. In contrast, among patients >60 years of age (n = 502), the OS was dismal, and there was no improvement over time

Gemtuzumab Ozogamicin Versus Best Supportive Care in Older Patients With Newly Diagnosed Acute Myeloid Leukemia Unsuitable for Intensive Chemotherapy: Results of the Randomized Phase III EORTC-GIMEMA AML-19 Trial

To compare single-agent gemtuzumab ozogamicin (GO) with best supportive care (BSC) including hydroxyurea as first-line therapy in older patients with acute myeloid leukemia unsuitable for intensive chemotherapy.status: publishe

Empiric versus pre-emptive antifungal strategy in high-risk neutropenic patients on fluconazole prophylaxis: a randomized trial of the European organization for Research and Treatment of cancer (EORTC 65091).

Empiric antifungal therapy is considered the standard-of-care for high-risk neutropenic patients with persistent fever. The impact of a pre-emptive, diagnostic-driven approach based on galactomannan (GM) screening and chest CT-scan on demand on survival and on the risk of invasive fungal disease (IFD) during the first weeks of high-risk neutropenia is unknown. Patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and allogeneic hematopoietic cell transplant recipients were randomly assigned to receive caspofungin empirically (Arm A) or pre-emptively (Arm B). All patients received fluconazole 400 mg daily as prophylaxis. The primary endpoint of this non-inferiority study was overall survival (OS) 42 days after randomization. Of 556 patients recruited, 549 were eligible: 275 in Arm A, 274 in Arm B. Eighty percent of the patients had AML or MDS requiring high-dose chemotherapy and 93% of them were in first induction phase. At day 42, the OS was not inferior in Arm B (96.7%; 95% confidence interval (CI), 93.8 - 98.3%) when compared to Arm A (93.1%; 95% CI, 89.3 - 95.5%). The rates of IFDs at day 84 were not significantly different, 7.7% (95%CI, 4.5-10.8%) in Arm B versus 6.6% (95%CI, 3.6-9.5%) in Arm A, respectively. The rate of patients receiving caspofungin was significantly lower in Arm B (27%) than in Arm A (63%) (p < 0.001). The pre-emptive antifungal strategy was safe for high-risk neutropenic patients given fluconazole as prophylaxis, halving the number of patients receiving antifungals without excess mortality or IFDs