The Role of Gemtuzumab Ozogamicin in Elderly AML Patients in Complete Remission.
Authors: Quintini Gerlando , Caramazza Domenica , Barbera Vincenzo , Maisano Silvana , Spadola Vincenzo , Siragusa Sergio , Abbadessa Vincenzo 
Published: October 2019

Abstract
The majority of patients (pts) with acute myeloid leukemia (AML) are diagnosed in their 6th and 7th decade of life. AML in elderly pts is associated with poor response to conventional chemotherapy and limited long-term survival, reflecting a higher incidence multidrug resistance mechanisms, a low bone marrow reserve which may prevent/delay the recovery of hematopoiesis after treatment, and the occurrence of co-morbidities. Gemtuzumab ozogamicin (GO) is an immunoconjugate with a humanized anti-CD33 that after internalization, releases a cytotoxic drug, calicheamicin; ≥80% of AML pts have myeloid blast cells that express the CD33 surface antigen. GO as a single agent has low antileukemic activity (Sievers et al, J Clin Oncol2001;19:3244–54). However, GO is being used at lower doses in combined chemotherapy regimens as induction or postremission therapy.
Results of limited studies to date appear encouraging and phase III trials are ongoing. We report our experience with 14 consecutive AML pts with a median age of 72 years (Table) treated between May 2004 and May 2007 with standard induction protocols. These included 1 or 2 courses of Fluda (FLAG, 10 pts) or non-Fluda induction regimens (daunorubicin+Ara-C, 1 pt, and idarubicin+Ara-C+etoposide, 4 pts). followed by 2 postremission courses of MFAC, consisting of fludarabine 15 mg/m2/bid IV on days 2–4, Ara-C 0.5 g/m2/bid IV on days 2–4, GO 4.5 mg/m2/d IV on day 1 with the addition of cyclosporin A 6 mg/kg bw IV followed by 16 mg/kg bw on days 1–2. Among 9 pts with available baseline cytogenetic data, 6 were in the poor-risk group and 3 were in the favorable-risk group. Pts were determined to have CD33-positive AML by analysis of bone marrow aspirates and by immunophenotyping. The rate of clinical remission (CR), characterized by ≤5% blast in the marrow, recovery of neutrophils to ≥1500 μ/L and RBC and platelet transfusion-independent, was 64.2% (9/14). Seven pts received 2 M-FAC courses, 2 pts did not receive the recommended second M-FAC because of disease progression (1 pt) or infection (1 pt). Subsequently, M-FAC was given to 2 pts twice every 4 weeks for maintenance therapy. Seven pts (50%) obtained a durable CR and the median response duration was 12 months. The most common non-hematological toxicities were infections and elevation of bilirubin and hepatic enzymes. Interestingly, no veno-occlusive disease was noted in these pts in CR and with low tumor load. This positive outcome compares favorably with that of the few published studies in which a similar approach was used, and further supports the use of GO in combined regimens for AML. MFAC was feasible and well tolerated, and the CR rates obtained in pts receiving MFAC after standard induction regimens were particularly encouraging. We conclude that combination with other cytotoxic agents may increase GO efficacy in elderly pts with AML.
Patient characteristics and outcome N=14 Median (range) Age, years 72 (56–83) CD33+ blasts, % 91.1 (84–95) WHO Performance Status Pts (%) 0–1 9(64%) 2 1 (7.1) 3 4 (28.6) Diagnosis AML de novo 7( 50) Secondary AML 1 (7.1) AML developed from MDS 5 (35.8) AML in first relapse 1 (7.1) Induction regimen Fluda (FLAG) 10 (71.4) Non-Fluda (3+7, ICE) 4 (28.6) Time from MDS to AML (yrs) < 1 2 (14.3) < 3 1 (7.1) unknown 2 (14.3) Cytogenetic group poor risk 6 (42.9) favorable risk 3 (21.4) not tested 5 (35.7) MFAC 1 course 9 (64.2) 2 courses 7 (50) Induction death rate 5 (35.7) MFAC death rate 1 (7.1) CR rate 7 (50) Median (range) Disease-free survival (months) 12 (2–24)