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.