sAML Pts Research Articles

Treatment of AML with Azacytidine (AZA): Current Results of the French ATU Program.

Background: AZA is an approved drug for MDS by FDA, currently being investigated in AML. ATUs are patient named programs launched by French health authorities for yet unapproved but promising drugs, and one is ongoing for AZA in MDS and AML.Patients: 108 AML pts from 29 centres included from Sept 2004 to June 2007 in this program, and who had completed at least one course of AZA, are analyzed. They received AZA 75 mg/m2/d (d 1–7) (SC) every 4 weeks, planned for a minimum of 4 courses.Results: Median age was 75 y [range 43–91], M/F was 66/42. 51 pts had AML without and 57 pts with preceding MDS, p-AML and s-AML, respectively (resp). Pts had M0, 1, 2, 3, 4, 5, 6, and 7, in 8, 16, 30, 0, 21, 15, 6 and 4% of cases, resp. 42, 17 and 12 pts were resistant, in first or second relapse, resp, to previous cytotoxic chemotherapy (CT), including intensive anthr-AraC CT in 64 pts and LD AraC in 7, while 37 pts (all with s-AML) were untreated. Karyotype was normal, fav (t(8;21), inv 16), unfav (−7/7q- or complex), int (all others) and NA in 38, 0, 45, 18 pts and 7 pts, resp. Pts received a median of 4 cycles [range 2–16]. Response was assessed only after 4 cycles, unless pts progressed before. Thus, 15 pts were not yet evaluable. Of the remaining 93 pts, 12 (13%) achieved CR, 34 (36%) PR, (OR=49%) and 43 (46%) were considered failure. 4 pts died before end of cycle 2, without evidence of progression. 35 of the 46 responders received maintenance therapy after response was achieved. Allogeneic SCT was performed in 5 responders (2 CR+3 PR). Myelosuppression lead to dose reduction in 16% pts and hospitalization in 17% pts but no toxic death was seen. Other side effects included local reactions (reversible with local NSAID) (19%), grade I-II GI disorders (52%). OR was 34% (11% CR+23% PR) in p-AML and 60% in s-AML pts (12% CR+48% PR) (p<0.05). In p-AML, OR was 75%, 17%, 11% for normal, int and unfav karyotype (p<0.001), while in s-AML, OR was 73%, 57%, 48% for normal, int and unfav karyotype (p=NS). Considering previous treatments, OR in p-AML was 63% and 24% for pts in 1st relapse and > 1 relapse/refractory, resp (p<0.05). In s-AML, OR was 61% and 46%, in previously treated or not pts, resp (p=NS). Median actuarial response duration was 6 months (m) (range 1–22+) in s-AML, and 3 m (1–28+) in p-AML. Median actuarial survival was 9 m [3–30] and 5 m [2–31+[in s- and p-AML, resp.Conclusion: In this very high risk population (in relapse, refractory or post MDS), AZA gave 49% CR and PR, which were higher in s-AML. A prognostic value of cytogenetics and of prior treatment for response was seen in p-AML, but was only marginal in s-AML. An update will be presented.

Gentuzumab-Ozogamicin, Citosine Arabinoside, G-CSF Combination (G-AraMy) in the Treatment of Secondary Acute Myeloid Leukemia in Elderly Patients.

Backround: Gentuzumab Ozogamicin (GO) is effective as single agent in the treatment of poor risk acute myeloid leukemia (AML) patients (pts). The aim of this study was to evaluate the efficacy and safety of a chemotherapy including growth factors, cytabine and GO in the treatment of secondary AML (sAML) elderly pts.Patients and Treatments: From September 2003 to September 2006, a total of 23 pts, median age 69 years (range 58–77) with sAML were enrolled in G-AraMy protocol which was divided in two phases. In the first phase from September 2003 to December 2004 11/23 pts received G-AraMy-1 treatment: rhG-CSF (5 μg/kg, on days 1–8), Aracytin as continuous perfusion (100 mg/m2 on days 4–8), GO (6 mg/m2 iv on day 9). In the second phase from January 2005 to September 2006 12 pts was treated according G-AraMy-2 protocol: G-CSF (5 μg/kg, on days 1–8), Ara-C as continuous perfusion (100 mg/m2 on days 2–8), GO (6 mg/m2 iv on day 9). In pts reaching complete (CR) or partial remission (PR), consolidation therapy was performed. In G-AraMy-1 this consisted of: G-CSF(5 μg/kg, on days 1–6), Ara-C as continuous perfusion (100 mg/m2 on days 2–6), GO (6 mg/m2 iv on day 7). G-Ara-My-2 group was consolidated with: G-CSF(5 μg/kg, on days 1–5), Ara-C (1 g/m2 every 12 hours on days 2–5), GO (6 mg/m2 iv on day 6).Results: Among the 23 treated pts 11 (48%) presented a post-MDS AML while 12 pts (52%) had received chemotherapy for a prior malignancy (3 Hodgkin's lymphoma, 5 breast, 2 thyroid, 1 gut, 1 bladder). Ten out 23 pts (43.5%) had previously received chemotherapy for AML being relapsed (4) or primary resistant pts (6) while 13 (56.5%) were untreated pts. Cytogenetic study was performed in all pts; karyotype was at “intermediate prognosis” in 11 cases, at “worse prognosis” in 7 cases, at “good prognosis” in 2 cases. In 3 pts no metaphases were observed. After induction and consolidation therapy 14 pts (6 group 1; 8 group 2) (61%) achieved a CR and 2 pts obtained PR. Five pts (22%) resulted refractory to treatment and 2 died during the aplasia period post induction treatment (1 due to sepsis, 1 due to cerebral haemorrhage). The most common adverse event was myelosuppression, as expected. No VOD was recorded. Seven pts (30%) developed documented infection (including pulmonary aspergillosis in 2 cases). Two pts died while in CR, 1 due to bladder cancer relapse and 1 to ischemic stroke. Nine of CR pts (39%) relapsed; at March 2007 5 pts (22%) are alive, of whom 1 are still in CR (4%). Median time to treatment failure (TTF) and median overall survival (OS) of whole population were 7.1 months (range 1–40.6+) and 8.6 months (range 1.7–40.6+) respectively. Stratifying pts according the two treatment groups median TTF was 4.4 months (range 3–10.5) in the first group and 7.2 months (range 1–40.6+) in the second; median OS was 6 months (range 1–13.6) in the first group and 9.1 months (range 1.7–40.6+) in the second.Conclusions: G-AraMy protocol could be considered an useful approach for elderly sAML pts considering the low reported side effects with a CR rate similar to that reported in literature. Unfortunately CR duration is brief. The modification of protocol schedule in the G-AraMy 2 group with the addition of more aggressive consolidation therapy seems to improve the duration of CR and OS.