Gemtuzumab-Ozogamicin as Post-Consolidation Therapy In Elderly Patients with Acute Myeloid Leukemia: a Pilot Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4357-4357
Author(s):  
Capelli Debora ◽  
Giorgia Mancini ◽  
Martina Chiarucci ◽  
Francesco Saraceni ◽  
Antonella Poloni ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Adverse Events ◽  
Elderly Patients ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Consolidation Therapy ◽  
Autologous Transplant ◽  
Poor Mobilizers ◽  
Acute Myeloid

Abstract Abstract 4357 The optimal post-remission treatment for elderly patients with acute myeloid leukemia (AML) is presently unknown. We evaluated safety and efficacy of low dose Gemtuzumab-Ozogamicin (GO) as post-remission late consolidation therapy in a cohort of 19 consecutive patients, enrolled in a pilot prospective study. Between June 1999 and February 2010 we observed 152 elderly patients, aged more than 60 years and affected by AML. One hundred and two patients (67%) were considered fit for aggressive therapy and received intensive induction and consolidation therapy including HD Ara-C, Idarubicine and Amifostine. Thirty-nine patients (38%) were over 70 years, 38% had a secondary disease, 35% unfavourable, 45% intermediate and 4 % favourable prognosis Karyotype. Those achieving successful mobilization received autologous transplant while poor mobilizers received a second consolidation with three monthly courses of GO 3 mg/sm i.v. followed by three other courses of GO administered every 3 months. Seventy-two patients achieved CR (69%) after induction: one patiente died in CR, 5 patients had a PS ≥2 and the remaining 66 were elegible for first consolidation. Fifty of these maintained the CR status and received a second consolidation: 19 with GO, 20 with Autologous transplant, and 6 with chemotherapy alone for patient decision. Five patients with a family donor received Allogeneic Transplant and were not included in this analysis. GO was well tolerated: no major adverse events were seen. We overall observed 18 WHO grade III/IV adverse events were all transitory and included hematological toxicity (n = 17), hypertransaminasemia (n = 1). Eight patients (42%) relapsed after GO consolidation and received a GO reinduction: five eventually died after a median follow-up of 13 months while three are still alive with a median follow up of 10 months. Five out of 20 patients died of transplant related toxicity (25%) and 9 relapsed (45%) after autologous transplant. All nine patients died of progressive disease. Five of the 6 patients receiving chemotherapy (83%) relapsed and died. Five years Overall survival was 22% and Disease Free Survival 29.5% in the whole cohort of patients (median follow-up: 50 mouths). The landmark analysis showed a superior outcome in patients receiving GO with a 60% 5 yrs OS and DFS (median follow-up: 60 months) in comparison with patients receiving autologous transplant (28% 5 yrs OS and DFS with median follow-up 70 months) and chemotherapy (17% 5 yrs OS and DFS with a median follow-up of 77 months) (p= 0.009). In conclusion patients receiving GO had a better outcome in comparison with patients receiving autologous transplant and chemothearapy. High percentages of poor mobilizers and transplant related mortality seem to jeopardize autologous transplant feasibility and safety in elderly patients. GO showed to be an alternative and feasible choice in our series, with a low relapse rate, and a low toxicity profile. Disclosures: Leoni: Celgene: Honoraria.

Addition of Cladribine to the Standard AML Treatment Improves Long-Term Outcome in High Tumor Burden and Older Than 40 Years Acute Myeloid Leukemia Patients. Five-Year Follow-Up of the Polish Adult Leukemia Group (PALG 1999 DAC vs. DA Study).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1795-1795
Author(s):  
Jerzy Holowiecki ◽  
Sebastian Grosicki ◽  
Tadeusz Robak ◽  
Slawomira Krzemien ◽  
Sebastian Giebel ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Tumor Burden ◽  
Consolidation Therapy ◽  
Term Outcome ◽  
Long Term Outcome ◽  
High Tumor Burden ◽  
Acute Myeloid

Abstract The goal of the study was to evaluate long-term outcome of acute myeloid leukemia (AML) patients treated within the PALG 1999 DAC vs, DA Study. Between 1999–2002, 445 patients, aged 18–60 years, were randomized to the induction DAC-7: daunorubicin 60 mg/m2/d iv 1–3; cytarabine 200 mg/m2/d ci 1–7; cladribine 5 mg/m2 2h inf. iv d 1–5 or standard DA-7 regimen (the same regimen without cladribine). Patients achieving CR received two courses of subsequent intensive consolidation: 1) HAM (HD AraC, mitoxantrone) 2) HD AraC with or without cladribine in the DAC-7 or DA-7 arm, respectively. In case of PR after the first induction course the same regimen was repeated, NR patients received CLAG (2-CDA, HD-AraC, G-CSF), regardless the randomization arm. Post-consolidation therapy was in both arms comparable. As previously reported, a single course of DAC-7 induction resulted in 17% higher CR rate compared to the DA-7 treatment. The difference was particularly pronounced in a population of patients >40 years and for those with initial WBC >100x109/L. In the latter subgroup also the overall CR rate (achieved after >=1 induction course) was higher in the DAC-7 arm (71% vs. 43%). [Leukemia. 2004 May;18(5):989–97] In the present report we analyzed long-term outcome (median follow-up 3.2 years) in the whole study group and in pre-defined subgroups taking into account initial tumor burden, age, cytogenetics, FAB subtype, and preceding myelodysplasia. At five years the overall survival (OS) rate equaled 31% for DAC-7 and 25% for DA-7 arm (p=0.42) and leukemia free survivall (LFS) 32% vs. 29% (p=0.38), respectively. The subgroup analysis revealed higher probability of the OS in patients with initial WBC ≥100 G/l assigned to DAC-7 compared to DA-7 arm (39% vs. 11%, p=0.02). The LFS rate and the probability of relapse equaled 50% and 32% (p=NS) and 36% and 68% (p=0.0497), respectively. In patients aged >40 years, the therapy containing cladribine was associated with improved LFS (30% for DAC-7 vs. 20% for DA-7, p=0.01), and a tendency to improved OS (28% vs. 18%, p=0.09). In this subgroup DAC-7 therapy resulted in reduced relapse incidence (60% vs. 69%, p=0.04).We conclude that addition of cladribine to induction/consolidation therapy of AML may improve long-term outcome in higher age ranges patients and in those with high tumor burden. The improvement results mainly from reduced risk of relapse, and, in patients with high initial WBC, from higher CR rate.

Efficacy of Low Dose Clofarabine Plus Intermediate Dose Cytarabine In An Unselected AML Refractory/Relapsed Adult Population

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4349-4349
Author(s):  
Claudio Romani ◽  
Emanuele Angelucci ◽  
Barbara Scappini ◽  
Mario Petrini ◽  
Martina Pettinau ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Nucleoside Analogue ◽  
Myeloid Leukemia ◽  
Low Dose ◽  
Haematological Toxicity ◽  
Allogeneic Transplantation ◽  
Gemtuzumab Ozogamicin ◽  
Acute Myeloid

Abstract Abstract 4349 Advanced AML in adult patients is a difficult challenge for hematologists with several unsuccessful approaches attempted during the last years. We tested the combination of the new nucleoside analogue Clofarabine in association with Cytarabine in a consecutive series of adult patients with advanced acute myeloid leukemia. From April 2007 to April 2010, 29 unselected advanced disease (not M3) acute myeloid leukemia (AML) patients were included in this multicenter study. There were 14 female and 15 male. Median age was 44 years (range 22–65). Twenty patients were in second or more advanced relapse and 9 had refractory disease to one or more chemotherapy regimens. Patients were treated with one cycle of five days clofarabine 22,5 mg/m2/day together with five days cytarabine 1 g/m2/day. The low dose (22,5 mg/m2) clofarabine was selected because of the burden of therapy that our patients had already received. In 19 patients gemtuzumab ozogamicin 6 mg/m2 was added by Centre physician decision. Toxicity and remission status were defined according with WHO criteria. Partial remission was considered as improvement of peripheral blood count and reduction of bone marrow blasts > 50%). Toxicity: Grade IV haematology toxicity was recorded in all patients. Extra haematological toxicity was as follows: four patients presented ≥ grade III cutaneous toxicity, ten hepatic toxicity; three patients mucositis. Eight patients experienced a life threatening infection while in aplasia (six systemic septicemia and two pneumonia) which were ultimately fatal in four. Disease response: overall, 16 over 29 patients (55%) entered in complete remission (CR) and 4 in partial remission. Overall response rate was 69%. Outcome: over the sixteen patients who entered complete remission: 1 was lost at follow up, 1 relapsed, 1 was treated with azacitidine and 2 with another cycle of clofarabine. These three patients who received a not transplant intensification therapy are, so far, alive in complete remission. In eleven patients an allogeneic transplantation (with an unrelated or sibling donor) was performed as intensification therapy: to date, 8 of these 11 patients are alive in continuous complete remission after a median follow up of 6,5 months (2-36) while three died (two while in CR). Overall 11 (68%) of the 16 patients who entered into complete remission are alive and well. The new nucleoside analogue Clofarabine showed efficacy and synergism with cytarabine in treating AML. Even if 29/29 patients experienced grade IV haematological toxicity, infection rate was low and suitable considering the status of the disease. Extra haematological toxicity was acceptable and easily manageable. Considering the dismal outcome of these patients, we believe that intensification should be performed to allow a continuous complete remission. Indeed we were able to transplant 11/16 patients, eight of which maintained the complete remission after transplantation. Notably, 3 patients remained alive in complete remission out of a transplantation approach. It is not possible to draw any conclusion about the role, if any, of gemtuzumab ozogamicin. In summary, we showed that low dose clofarabine plus cytarabine because of efficacy and low extra-hematology toxicity could be a real bridge to allogeneic transplantation in these very poor risk pre-treated acute leukaemia patients. A longer follow up is awaited. Disclosures: Off Label Use: Clofarabine in refractpry/relapsed AML.

Sorafenib in Combination With Intensive Chemotherapy in Elderly Patients With Acute Myeloid Leukemia: Results From a Randomized, Placebo-Controlled Trial

2013 ◽  
Vol 31 (25) ◽  
pp. 3110-3118 ◽  
Author(s):  
Hubert Serve ◽  
Utz Krug ◽  
Ruth Wagner ◽  
M. Cristina Sauerland ◽  
Achim Heinecke ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Kinase Inhibitor ◽  
Controlled Trial ◽  
Intensive Chemotherapy ◽  
Consolidation Therapy ◽  
Subgroup Analyses ◽  
Acute Myeloid

Purpose The prognosis of elderly patients with acute myeloid leukemia (AML) is still dismal even with intensive chemotherapy. In this trial, we compared the antileukemic activity of standard induction and consolidation therapy with or without the addition of the kinase inhibitor sorafenib in elderly patients with AML. Patients and Methods All patients received standard cytarabine and daunorubicin induction (7+3 regimen) and up to two cycles of intermediate-dose cytarabine consolidation. Two hundred one patients were equally randomly assigned to receive either sorafenib or placebo between the chemotherapy cycles and subsequently for up to 1 year after the beginning of therapy. The primary objective was to test for an improvement in event-free survival (EFS). Overall survival (OS), complete remission (CR) rate, tolerability, and several predefined subgroup analyses were among the secondary objectives. Results Age, sex, CR and early death (ED) probability, and prognostic factors were balanced between both study arms. Treatment in the sorafenib arm did not result in significant improvement in EFS or OS. This was also true for subgroup analyses, including the subgroup positive for FLT3 internal tandem duplications. Results of induction therapy were worse in the sorafenib arm, with higher treatment-related mortality and lower CR rates. More adverse effects occurred during induction therapy in the sorafenib arm, and patients in this arm received less consolidation chemotherapy as a result of higher induction toxicity. Conclusion In conclusion, combination of standard induction and consolidation therapy with sorafenib in the schedule investigated in our trial is not beneficial for elderly patients with AML.

scholarly journals A phase II trial of induction and consolidation therapy of acute myeloid leukemia with weekly oral idarubicin alone in poor risk elderly patients

Leukemia ◽  
1999 ◽  
Vol 13 (10) ◽  
pp. 1491-1496 ◽  
Author(s):  
R Bouabdallah ◽  
F Lefrère ◽  
C Rose ◽  
P Chaïbi ◽  
J-L Harousseau ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Phase Ii ◽  
Myeloid Leukemia ◽  
Phase Ii Trial ◽  
Consolidation Therapy ◽  
Poor Risk ◽  
Acute Myeloid

High-dose cytarabine and daunorubicin as consolidation therapy for acute myeloid leukemia in first remission: long-term follow-up and results.

1989 ◽  
Vol 7 (9) ◽  
pp. 1260-1267 ◽  
Author(s):  
S N Wolff ◽  
R H Herzig ◽  
J W Fay ◽  
G L Phillips ◽  
H M Lazarus ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Myeloid Leukemia ◽  
High Dose ◽  
Allogeneic Bone ◽  
Consolidation Therapy ◽  
High Dose Cytarabine ◽  
Acute Myeloid

In an effort to increase the proportion of patients with acute myeloid leukemia (AML) remaining in continued complete remission (CCR), we administered intensive postremission consolidation therapy with high-dose cytarabine (Ara-C) and daunorubicin. Eighty-seven patients, with a median age of 38 years (range, 7 to 71), received consolidation therapy after first complete remission was obtained with standard induction chemotherapy that included conventional doses of Ara-C. Consolidation therapy consisted of from one to three cycles of high-dose Ara-C (3 g/m2 intravenously [IV] over 1 hour every 12 hours for 12 doses) followed by daunorubicin (30 mg/m2/d IV bolus for 3 days). After completion of the high-dose Ara-C and daunorubicin, no further therapy was administered. Myelosuppression encountered with consolidation resulted in a median duration of neutropenia and thrombocytopenia of 3 weeks. Four patients (5%) died during consolidation due to infection and/or hemorrhage; 59% of patients experienced severe but nonfatal infectious or extramedullary organ toxicity. With a median follow-up of more than 3.5 years from diagnosis, the proportion of patients, by Kaplan-Meier product-limit estimate, remaining in CCR is 49% (95% confidence limits, 37% to 61%). In a Cox multivariate analysis, only age significantly (P less than .001) influenced the probability of remaining in CCR. The probability of remaining in CCR was 83%, 50%, and 23% for age groups of 25 or less, 26 to 45, and more than 45 years, respectively. These survival curves all have stable long-term plateaus, suggesting cure. In this study, the administration of brief, intensive nonmarrow ablative chemotherapy resulted in a large proportion of patients with AML remaining in CCR, results similar to those reported with allogeneic bone marrow transplantation. Relapse of acute leukemia was still the major reason for therapy failure, suggesting that more effective or additional postremission therapy will be required to further improve the likelihood of cure especially for older patients.

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