Page 134 - 2019_01-Haematologica-web

N. Niktoreh et al.
GO in combination with cytarabine or other agents fol- lowing the failure of treatment after first early relapse (n=20 of 37, 54%) (data not shown). When GO was admin- istered as monotherapy, higher doses were used (Figure 1).
Safety and toxicities
Among 71 patients who were evaluated for AEs during the first cycle of treatment, most common AEs were grade 3/4 infections or febrile neutropenia (61 events in 49 patients, 69%) (Table 3). Two patients suffered from sep- sis and were successfully managed with supportive and anti-bacterial therapy. Gastrointestinal (GI) symptoms (11 grade 1/2 events in 11 patients and 4 grade 3/4 events in 4 patients) and immunologic reactions such as infusion- related fever, chills, or hypotension (7 grade-1/2 events in 7 patients and 5 grade 3/4 events in 5 patients) were most frequently observed after infections. Due to interference with other treatments, GI events could not be assigned to GO with certainty.
Among grade 3 and 4 AEs, febrile neutropenia was most frequently observed in both groups of patients with monotherapy and combination therapy as well as in all different groups of patients independently of their previ- ous treatments (FLA/G or FLA/G+DX or patients with HSCT prior to GO) (data not shown). The majority (4 of 5) of patients with severe infusion-related immunological reactions to GO treatment, had previously received GO as monotherapy with higher doses compared to patients with combination therapy (data not shown).
Veno-occlusive disease (VOD) occurred in 3 patients who received GO as monotherapy (one cycle) at doses of 6, 7.5, and 9 mg/m2. All 3 patients had FLA/G+DX as treat- ment before GO, and received defibrotide as prophylaxis against VOD. Two of these patients were treated with HSCT prior to treatment with GO (6 or 7.5 mg/m2). The patient treated with 6 mg/m2 GO had a previous history of VOD and developed a GO-related VOD before the scheduled HSCT that was successfully treated without late effects or events. The other 2 patients could not receive HSCT after treatment with GO and both died. Cause of death in one of them was disease (leukemic) pro-
Figure 1. Gemtuzumab ozogamicin (GO) dosage. GO dosage based on admin- istration with cytarabine or other agents. AML: acute myeloid leukemia; n.d. : no data.
gression, and the other patient experienced exacerbation of a pre-existing cardiomyopathy leading to death 24 days after GO treatment. In addition, treatment with GO resulted in exacerbation of previous symptoms in 2 patients (pulmonary aspergillosis infection or gastroin- testinal toxicity) and, due to overlap with other treatments and HSCT, the consequences of these AEs could not be exclusively correlated to GO (Table 3). Similarly, the con- sequences of different AEs in one patient with GO-related cytokine syndrome and pre-existing respiratory distress could not be distinguished from each other (Table 3). The respiratory distress in this patient was related to an apla- sia-associated pneumonia which was caused by teatments before GO.
Outcome
With a median follow up time of 4.3 years (range: 1-5 years), the probability of 4-year OS after treatment with
Figure 2. Survival after gemtuzumab ozogamicin (GO). (A) 4-year probability of overall survival (OS) in all patients. (B) 4-year probability of OS in different dis- ease statuses. (C) 4-year probability of OS based on administration of hematopoietic stem cell transplantation (HSCT). pOS: probablity of OS; n: num- ber of patients; AML: acute myeloid leukemia; SE: Standard Error.
A
B
C
124
haematologica | 2019; 104(1)