PURPOSE: To determine the antitumor activity and safety of a combination of gemtuzumab ozogamicin (GO), intermediate-dose cytarabine, and mitoxantrone (MIDAM) in patients with refractory or relapsed CD33(+) acute myeloid leukemia (AML). PATIENTS AND METHODS: We treated 62 patients with refractory (n = 18) or relapsed (n = 44) CD33(+) AML. Median age was 55.5 years. Salvage regimen consisted of GO 9 mg/m(2) on day 4, cytarabine 1 g/m(2) every 12 hours on days 1 through 5, and mitoxantrone 12 mg/m(2)/d on days 1 through 3. Median follow-up time was 26.5 months. RESULTS: Thirty-one patients (50%) achieved complete remission (CR), and eight patients (13%) had CR with delayed platelet recovery (CRp); the overall response (OR; CR + CRp) rate was 63%. A significantly higher OR rate was achieved in patients who had relapsed versus refractory AML (73% v 39%, respectively; P = .007) and patients with CD33 expression more than 98% of the blast population versus less than 98% (79% v 52.3%, respectively; P = .03). The overall, event-free, and disease-free survival rates were 41%, 33%, and 53% at 2 years, respectively. Leukocytosis more than 20,000/microL at MIDAM therapy, high-risk cytogenetics, and absence of postremission therapy were adverse prognostic factors. Age, disease status, and/or CD33 expression did not influence survival parameters. Four early toxic deaths occurred; a grade 3 to 4 hyperbilirubinemia rate of 16% was observed, and two patients had veno-occlusive disease (3%). CONCLUSION: The MIDAM regimen seems to be an effective salvage regimen for refractory/relapsed CD33(+) AML patients. These encouraging results support the need for a randomized phase III trial before considering this combination of GO and chemotherapy as superior or the standard of care treatment for refractory/relapsed CD33(+) AML patients.
RCT Entities:
PURPOSE: To determine the antitumor activity and safety of a combination of gemtuzumab ozogamicin (GO), intermediate-dose cytarabine, and mitoxantrone (MIDAM) in patients with refractory or relapsed CD33(+) acute myeloid leukemia (AML). PATIENTS AND METHODS: We treated 62 patients with refractory (n = 18) or relapsed (n = 44) CD33(+) AML. Median age was 55.5 years. Salvage regimen consisted of GO 9 mg/m(2) on day 4, cytarabine 1 g/m(2) every 12 hours on days 1 through 5, and mitoxantrone 12 mg/m(2)/d on days 1 through 3. Median follow-up time was 26.5 months. RESULTS: Thirty-one patients (50%) achieved complete remission (CR), and eight patients (13%) had CR with delayed platelet recovery (CRp); the overall response (OR; CR + CRp) rate was 63%. A significantly higher OR rate was achieved in patients who had relapsed versus refractory AML (73% v 39%, respectively; P = .007) and patients with CD33 expression more than 98% of the blast population versus less than 98% (79% v 52.3%, respectively; P = .03). The overall, event-free, and disease-free survival rates were 41%, 33%, and 53% at 2 years, respectively. Leukocytosis more than 20,000/microL at MIDAM therapy, high-risk cytogenetics, and absence of postremission therapy were adverse prognostic factors. Age, disease status, and/or CD33 expression did not influence survival parameters. Four early toxic deaths occurred; a grade 3 to 4 hyperbilirubinemia rate of 16% was observed, and two patients had veno-occlusive disease (3%). CONCLUSION: The MIDAM regimen seems to be an effective salvage regimen for refractory/relapsed CD33(+) AMLpatients. These encouraging results support the need for a randomized phase III trial before considering this combination of GO and chemotherapy as superior or the standard of care treatment for refractory/relapsed CD33(+) AMLpatients.
Authors: Susan O'Brien; David A Rizzieri; Norbert Vey; Farhad Ravandi; Utz O Krug; Mikkael A Sekeres; Mike Dennis; Adriano Venditti; Donald A Berry; Tove Flem Jacobsen; Karin Staudacher; Trygve Bergeland; Francis J Giles Journal: Br J Haematol Date: 2012-06-15 Impact factor: 6.998
Authors: Richard M Stone; Barry Moser; Ben Sanford; Philip Schulman; Jonathan E Kolitz; Steven Allen; Wendy Stock; Ilene Galinsky; Ravi Vij; Guido Marcucci; David Hurd; Richard A Larson Journal: Leuk Res Date: 2010-08-04 Impact factor: 3.156
Authors: P Chevallier; M Labopin; N Milpied; K Bilger; G Socié; I Yakoub-Agha; M Michallet; C-E Bulabois; S Maury; Y Beguin; J-O Bay; D Blaise; N Maillard; G Guillerm; E Daguindeau; N Raus; M Mohty Journal: Bone Marrow Transplant Date: 2013-12-02 Impact factor: 5.483
Authors: Tim Pfeiffer; Michael Schleuning; Jiri Mayer; Karl-Heinz Haude; Johanna Tischer; Stefanie Buchholz; Donald Bunjes; Gesine Bug; Ernst Holler; Ralf G Meyer; Hildegard Greinix; Christof Scheid; Maximilian Christopeit; Susanne Schnittger; Jan Braess; Günter Schlimok; Karsten Spiekermann; Arnold Ganser; Hans-Jochem Kolb; Christoph Schmid Journal: Haematologica Date: 2012-09-14 Impact factor: 9.941