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acute myeloid leukemia; gemtuzumab ozogamicin; prognosis; treatment
One-hundred and four adults with newly diagnosed or relapsed/refractory acute myeloid leukemia (AML) were treated with fractionated doses of gemtuzumab ozogamicin (GO) at one-single French center over a 10-year period. We attempted to define predictive factors for response and survival. The overall response rate was 70% (86% in newly diagnosed and 67% in relapsed/refractory AML). Disease-free survival (DFS) and overall survival at 3 years after GO treatment was 31% and 29%, respectively. Mortality during induction was 7%. Among remitters, allogeneic hematopoietic stem cell transplantation can be performed in 33 cases (45%). DFS at 3 years was 54%. Incidences of transplant-related mortality, grade ? 3 acute graft-versus-host (GvH) disease, and extensive chronic GvH disease were 15%, 12%, and 27%, respectively.No sinusoidal obstruction syndromes were reported among allografted patients as among the other patients in the studied cohort. GO-based chemotherapy is a viable option for treatment of newly diagnosed and relapsed/refractory AML patients, and is a feasible schedule as a bridge to allogeneic transplant.
2. Appelbaum FR, Bernstein ID. Gemtuzumab ozogamicin for acute myeloid leukemia. Blood 2017; 130:2373-2376.
3. Amadori S, Suciu S, Selleslag D, et al. Randomized trial of two schedules of low-dose gemtuzumabozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukaemia groups (AML-19). Br J Haematol 2010; 149:376-382.
4. Lambert J, Pautas C, Terré C, et al. Gemtuzumab ozogamicin for de novo acute myeloid leukemia: final efficacy and safety updates from the open-label, phase III ALFA-0701 trial. Haematologica 2019; 104:113-119.
5. Burnett AK, Hills RK, Hunter AE, et al. The addition of gemtuzumabozogamicin to low-dose AraC improves remission rate but does not significantly prolong survival in older patients with acute myeloid leukaemia: results from the LRF AML14 and NCRI AML16 pick-a-winner comparison. Leukemia 2013; 27:75-81.
6. Nand S, Othus M, Godwin JE, et al. A phase 2 trial of azacitidine and gemtuzumab ozogamicin therapy in older patients with acute myeloid leukemia. Blood 2013; 122:3432-3439.
7. Döhner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010; 115:453-474.
8. Malard F, Labopin M, Stuhler G, et al. Sequential intensified conditioning regimen allogeneic hematopoietic stem cell transplantation in adult patients with intermediate- or high-risk acute myeloid leukemia in complete remission: a study from the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 2017; 23:278-284.
9. Medeiros BC. Interpretation of clinical endpoints in trials of acute myeloid leukemia. Leuk Res 2018; 68:32-39.
10. Stone RM, Moser B, Sanford B, et al. High dose cytarabine plus gemtuzumab ozogamicin for patients with relapsed or refractory acute myeloid leukemia: Cancer and Leukemia Group B study 19902. Leuk Res 2011; 35:329-333.
11. Specchia G, Pastore D, Carluccio P, et al. Gemtuzumab ozogamicin with cytarabine and mitoxantrone as a third-line treatment in a poor prognosis group of adult acute myeloid leukemia patients: a single-center experience. Ann hematol 2007; 86:425-428.
12. Cortes J, Tsimberidou AM, Alvarez R, et al. Mylotarg combined with topotecan and cytarabine in patients with refractory acute myelogenous leukemia. Cancer Chemother Pharmacol 2002; 50:497-500.
13. Fianchi L, Pagano L, Leoni F, et al. Gemtuzumab ozogamicin, cytosine arabinoside, G-CSF combination (G-AraMy) in the treatment of elderly patients with poor-prognosis acute myeloid leukemia. Ann Oncol 2008; 19:128-134.
14. Piccaluga PP, Martinelli G, Rondoni M, et al. Gemtuzumab ozogamicin for relapsed and refractory acute myeloid leukemia and myeloid sarcomas. LeukLymphoma 2004; 45:1791-1795.
15. Apostolidou E, Cortes J, Tsimberidou A, et al. Pilot study of gemtuzumab ozogamicin, liposomal daunorubicin, cytarabine and cyclosporine regimen in patients with refractory acute myelogenous leukemia. Leuk Res 2003; 27:887-891.
16. Petersdorf SH, Kopecky KJ, Slovak M, et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood 2013; 121:4854-4860.
17. Castaigne S, Pautas C, Terré C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomized, open-label, phase 3 study. Lancet 2012; 379:1508-1516.
18. Pilorge S, Rigaudeau S, Rabian F, et al. Fractionated gemtuzumab ozogamicin and standard dose cytarabine produced prolonged second remissions in patients over the age of 55 years with acute myeloid leukemia in late relapse. Am J Hematol 2014; 89:399-403.
19. Chantepie SP, Reboursiere E, Mear JB, et al. Gemtuzumab ozogamicin with intensive chemotherapy in relapsed or refractory acute myeloid leukemia. Leuk Lymphoma 2015; 56:2326-2330.
20. Taksin AL, Legrand O, Raffoux E, et al. High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the ALFA group. Leukemia 2007; 21:61-71.
21. Breems DA, Van Putten WL, Huijgens PC, et al. Prognostic index for adult patients with acute myeloid leukemia in first relapse. J ClinOncol 2005; 23:1969-1978.
22. Biggs JC, Horowitz MM, Gale RP, et al. Bone marrow transplants may cure patients with acute leukemia never achieving remission with chemotherapy. Blood 1992; 80:1090-1093.
23. Debureaux PE, Labopin M, Mamez AC, et al. Fractionated gemtuzumab ozogamicin in association with high dose chemotherapy: a bridge to allogeneic stem cell transplantation in refractory and relapsed acute myeloid leukemia. Bone Marrow Transplant 2019; doi: 10.1038/s41409-019-0690 [Epub ahead of print].
24. Tarlock K, Alonzo TA, Gerbing RB, et al. Gemtuzumab ozogamicin reduces relapse risk in FLT3/ITD acute myeloid leukemia: a report from the Children’s Oncology Group. Clin Cancer Res 2016; 22:1951-1957.
25. Pollard JA, Alonzo TA, Loken M, et al. Correlation of CD33 expression level with disease characteristics and response to gemtuzumab ozogamicin containing chemotherapy in childhood AML. Blood 2012; 119:3705-3711.
26. Khan N, Hills RK, Virgo P, et al. Expression of CD33 is a predictive factor for effect of gemtuzumab ozogamicin at different doses in adult AML. Leukemia 2017; 31:1059-1068.
27. Thomas X, Raffoux E, Renneville A, et al. Outcome of treatment after first relapse in younger adults with acute myeloid leukemia initially treated by the ALFA-9802 trial. LeukRes 2012; 36:1112-1118.
28. Craddock C, Labopin M, Pillai S, et al. Factors predicting outcome after unrelated donor stem cell transplantation in primary refractory acute myeloid leukemia. Leukemia 2011; 25:808-813.
29. Daver N, Kantarjian H, Ravandi F, et al. A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome. Leukemia 2016; 30:268-273.
30. Giles FJ, Kantarjian HM, Kornblau SM, et al. Mylotarg (gemtuzumab ozogamicin) therapy is associated with hepatic venoocclusive disease in patients who have not received stem cell transplantation. Cancer 2001; 92:406-413.
31. Tack DK, Letendre L, Kamath PS, Tefferi A. Development of hepatic veno-occlusive disease after Mylotarg infusion for relapsed acute myeloid leukemia. Bone Marrow Transplant 2001; 28:895-897.
32. Rajvanshi P, Shulman HM, Sievers EL, et al. Hepatic sinusoidal obstruction after gemtuzumab ozogamicin (Mylotarg) therapy. Blood 2002; 99:2310-2314.
33. McKoy JM, Angelotta C, Bennett CL, et al. Gemtuzumab ozogamicin-associated sinusoidal obstruction syndrome (SOS): an overview from the research on adverse drug events and reports (RADAR) project. Leuk Res 2007; 31:599-604.
34. Hauswirth AW, Florian S, Printz D, et al. Expression of the target receptor CD33 in CD34+/CD38?/CD123+ AML stem cells. Eur J Clin Invest 2007; 37:73-82.
35. Walter RB, Appelbaum FR, Estey EH, Bernstein ID. Acute myeloid leukemia stem cells and CD33-targeted immunotherapy. Blood 2012; 119:6198-6208.
36. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature 2011; 414:105-111.
37. Baer MR, Stewart CC, Dodge RK, et al. High frequency of immunophenotype changes in acute myeloid leukemia at relapse: implications for residual disease detection (Cancer and Leukemia Group B Study 8361). Blood 2001; 97:3574-3580.