Primary end points -evaluation of safety in terms of:

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1 Primary end points -evaluation of safety in terms of: TRD; severe hematological and extrahematological toxicity -evaluation of CR rate. Secondary end points 1-days of hospitalization during induction therapy; 2-percentage of patients suitable for PBSC collection and ASCT 3-OS and LFS

2 PBSC Collect INDUCTION PHASE* d 1 d 2 d 3 d 4 ARA-C* 3 g/mq IDA*
40 mg/mq Amifostine d 5 IDA 30 mg/mq Amifostina CONSOLIDATION PHASE ARA-C 3 g/mq ARA-C 3 g/mq ARA-C 3 g/mq ARA-C 3 g/mq PBSC Collect d 1 d 2 d 3 d 3 d 4 *IN PTS > 70 yrs ARA-C and Ida doses have been reduced by 30%.

3 15 pts >3 x 106 PBPC collected 14 pts ALTERNATIVE THERAPY
42 patients Amifostine+IDA+ARA-C 10 NR 1 ED 29 CR 2 PR 3 CR (II line) ORR 31/41 (76%), with II line 34/41 (83%) 2 RELAPSE 32 CONSOLIDATION COURSE 2 TRD 29 CCR evaluable for collection 1 RELAPSE 15 pts >3 x 106 PBPC collected 14 pts ALTERNATIVE THERAPY 1 RELAPSE RESULTS After the first induction course 29 patients achieved CR and 2 PR; 10 patients were NR, but 3 of them, who attained a significant blast clearence in the bone marrow, achieved CR after the second induction course of chemotherapy; we observed one only TRD (2.3%). The final ORR was 83% with a CR rate of …. Before starting the consolidation therapy we observed 2 relapses, so 32 out of the 34 patients achieving CR received the consolidation therapy which was based on the association of ARA-C intermediate dose plus Lyposomal Doxorubicin in .. Cases and the same schedule of IDA-Amifostine plus HD-ARA-C in the other……. We observed 2 TRD during the consolidation therapy (4…%) and 29 patients maintained CR and were evaluable for the PBPC collection. 15 patients were able to collect>3x10e6CD34+cells/Kg while 14 failed to mobilize a sufficient number of CD34+ cells; 1 patient relapsed very quikly after collecting more than …CD34+ cell; consequently only 14 patients could be autotransplanted with TBI-free conditioning regimens including HDM. The 14 patients who could not be autotransplanted received a second attempt of mobilising chemotherapy, without attaining a relevant CD 34+ cell peak and were followed without any further therapy in .. Cases or received low dose Gemtozumab in .. Cases. We observed 3 TRD in the 14 patients autotransplanted while the remaining 11 patients showed a promp and complete engraftment. Overally 9 patients are in first complete remission with a median follow-up of … (range ….) with a median LFS of …. The OS was and …. 14 PBSC AUTOTRANSPLANT 3 TRM 1 DEC (in CR) 11 EVALUABLE 3 CCR 6 CCR

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6 we did not observe a superior OS in those patients
…….Intriguingly, we did not observe a superior OS in those patients who received consolidation with ASCT, compared with those who received another consolidation (???) due to an insufficient PBSC mobilization………….

7 The second part of history…..
123 patients with non-M3 AML, median age 71 years (range 55-89), were observed in our institution. All patients were preliminary evaluated according to a simplified MGA so we were able to separate fit patients from unfit or frail patients. 79 fit patients were enrolled in this protocol 27 (35%) had AML secondary to MDS Clinica di Ematologia-Università Politecnica delle Marche

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9 Prospective study: design
CR after intensive induction with Memorial-Amifostine Consolidation CHT with HD-ARAC-Ida-Amif Sufficient PBSC harvest (Cd34+>3,5x10e6/kg) YES NO ASCT MYLOTARG 5 mgx3/4 wks

10 Clinica di Ematologia-Università Politecnica delle Marche
LOW DOSE Gentuzumab Ozogamicin, after intensive induction in older AML patients: results in 13 patients in a single centre institution Poloni A, Trappolini S, Costantini B, Capelli D, Troiani E, Mancini G, Discepoli G, Montanari M, Gini G, Scortechini I, Leoni P and Olivieri A Rationale: low dose GO as post-remission approach after CR, in order to eliminate the minimal residual disease in elderly patients enrolled in a pilot prospective study Clinica di Ematologia-Università Politecnica delle Marche

11 Clinica di Ematologia-Università Politecnica delle Marche
78 elderly AML patients, eligible for aggressive chemotherapy: 57 (73%) achieved CR .....among these 48 (84%) received first consolidation with intensive chemotherapy and were planned to receive a further consolidation with ASCT or low dose GO in case of PBSC collection failure: patients successfully achieved PBSC collection and 19 undergo ASCT: in this subset we observed 4 TRD (21%) with 9 patients relapsing and 6 patients still alive in CR with a median follow-up of 60 months (range, 7-100). Therteen patients, that failed PBSC mobilization, have been furtherly consolidated with GO at the dose of 3 mg/m2 for three times, monthly, with a median follow-up was 23 months (range, 6-62) Clinica di Ematologia-Università Politecnica delle Marche

12 Dopo terapia d’Induzione, 57 (72,1%) dei 79 pazienti hanno raggiunto la remissione completa
Strategia terapeutica nei 42 pazienti in RC continuativa dopo 1° consolidamento

13 Overall Survival stratificata per tipo di terapia
Tutte le sopravvivenze sono state considerate dalla fine del I° consolidamento e non sono stati considerati gli allotrapianti

14 Disease Free Survival stratificata per tipo di terapia

15 CARATTERISTICHE DEI 13 PAZIENTI SOTTOPOSTI A TERAPIA CON MYLOTARG
Sesso Iperleucocitosi Malattia secondaria Cariotipo Età Status Pz 1 M NO intermedio <70 Vivo RC Pz 2 >70 Vivo Relapse Pz 3 >10000 non valutabile Morto Pz 4 F favorevole Pz 5 SI Pz 6 Non valutabile Pz 7 Pz 8 Pz 9 Non favorevole Pz 10 Pz 11 Pz 12 Pz 13

16 TOSSICITA’ MYLOTARG Tossicità di grado III/IV (secondo WHO):
- 9 casi di tossicità ematologica - 1 caso di ipertransaminasemia - 3 reazioni di tipo allergico - non si sono osservati eventi avversi maggiori Dei 13 pazienti 2 sono ricaduti e deceduti rispettivamente dopo 11 e 19 mesi dall’ultima infusione di Gemtuzumab-Ozogamicin; un paziente è ricaduto dopo 20 mesi ed ha ottenuto una seconda remissione completa con un ciclo chemioterapico di reinduzione; un altro paziente, ricaduto dopo 32 mesi, ha ricevuto una altro ciclo di consolidamento con GO dopo una seconda remissione completa mantenuta per circa 12 mesi. Quindi 10 pazienti sono vivi e attualmente in remissione completa.

17 Proposal