Safety of gemtuzumab ozogamicin as monotherapy or combination therapy in an expanded-access protocol for patients with relapsed or refractory acute myeloid leukemia

Figures & data

Table 1. Summary of treatment exposure to GO.

Prescribed dose, n (%)	All patients			Age <18 years^a		Age ≥ 18 years
	AML monotherapy n = 139	AML combination therapy n = 183	APL treatment n = 9	AML monotherapy n = 21	AML combination therapy n = 84	AML monotherapy n = 118	AML combination therapy n = 99	APL treatment n = 9
Received only one dose
3 mg/m^2	10 (7.2)	96 (52.5)	0	2 (9.5)	47 (56.0)	8 (6.8)	49 (49.5)	0
6 mg/m^2	14 (10.1)	1 (0.5)	3 (33.3)	2 (9.5)	1 (1.2)	12 (10.2)	0	3 (33.3)
7.5 mg/m^2	1 (0.7)	0	0	1 (4.8)	0	0	0	0
9 mg/m^2	21 (15.1)	1 (0.5)	1 (11.1)	2 (9.5)	0	19 (16.1)	1 (1.0)	1 (11.1)
Other^†	2 (1.4)	4 (2.2)	0	2 (9.5)	4 (4.8)	0	0	0
Received doses on 2 or more days
3 mg/m^2	33 (23.7)	76 (41.5)	0	5 (23.8)	30 (35.7)	28 (23.7)	46 (46.5)	0
6 mg/m^2	11 (7.9)	0	4 (44.4)	0	0	11 (9.3)	0	4 (44.4)
7.5 mg/m^2	4 (2.9)	0	0	3 (14.3)	0	1 (0.8)	0	0
9 mg/m^2	29 (20.9)	0	1 (11.1)	2 (9.5)	0	27 (22.9)	0	1 (11.1)
Other^b	14 (10.1)	5 (2.7)	0	2 (9.5)	2 (2.4)	12 (10.2)	3 (3.0)	0

Patients who received more than one dose of GO, regardless of dosage, were only reported under ‘Received doses on 2 or more days.’ Patients were allowed to reenroll in the study. Such patients are summarized according to each enrollment treatment. AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; GO: gemtuzumab ozogamicin.

^aNo patients aged <18 years were treated for APL.

^bPatients in the ‘Other’ category were either treated with a different dose from that listed or, for the ‘Received doses on 2 or more days’ category, were not treated with the same prescribed dose for all treatment days.

Table 2. Most common grade ≥3 AEs occurring in ≥15% of all patients in any group.

AE, n (%)	AML monotherapy n = 139	AML combination therapy n = 183	APL treatment n = 9
All-causality AEs
Any AE	134 (96.4)	172 (94.0)	9 (100.0)
Anemia	54 (38.8)	86 (47.0)	2 (22.2)
WBC count decrease	52 (37.4)	66 (36.1)	2 (22.2)
Platelet count decrease	50 (36.0)	65 (35.5)	3 (33.3)
Febrile neutropenia	44 (31.7)	69 (37.7)	7 (77.8)
Disease progression	32 (23.0)	15 (8.2)	1 (11.1)
Lymphocyte count decrease	29 (20.9)	52 (28.4)	0
Hypokalemia	22 (15.8)	44 (24.0)	0
Neutrophil count decrease	20 (14.4)	57 (31.1)	2 (22.2)
Lung infection	3 (2.2)	8 (4.4)	2 (22.2)
Treatment-related AEs
Any treatment-related AE	84 (60.4)	102 (55.7)	7 (77.8)
WBC count decrease	44 (31.7)	21 (11.5)	1 (11.1)
Platelet count decrease	35 (25.2)	24 (13.1)	3 (33.3)
Anemia	34 (24.5)	42 (23.0)	1 (11.1)
Febrile neutropenia	23 (16.5)	35 (19.1)	6 (66.7)

AE: adverse event; AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; WBC: white blood cell.

Table 3. Grade ≥3 all-causality AEs occurring in ≥15% of patients in any group: analysis by age.

AE, n (%)	Age <18 years^a		Age ≥18 years
	AML monotherapy n = 21	AML combination therapy n = 84	AMLmonotherapy n = 118	AMLcombination therapy n = 99	APL treatment n = 9
Any AE	21 (100.0)	78 (92.9)	113 (95.8)	94 (94.9)	9 (100.0)
Anemia	10 (47.6)	41 (48.8)	44 (37.3)	45 (45.5)	2 (22.2)
Febrile neutropenia	10 (47.6)	33 (39.3)	34 (28.8)	36 (36.4)	7 (77.8)
Disease progression	5 (23.8)	2 (2.4)	27 (22.9)	13 (13.1)	1 (11.1)
Device-related infection	4 (19.0)	5 (6.0)	0	3 (3.0)	0
Neutrophil count decrease	5 (23.8)	41 (48.8)	15 (12.7)	16 (16.2)	2 (22.2)
Platelet count decrease	11 (52.4)	47 (56.0)	39 (33.1)	18 (18.2)	3 (33.3)
WBC count decrease	7 (33.3)	43 (51.2)	45 (38.1)	23 (23.2)	2 (22.2)
Hypokalemia	7 (33.3)	25 (29.8)	15 (12.7)	19 (19.2)	0
Lymphocyte count decrease	3 (14.3)	26 (31.0)	26 (22.0)	26 (26.3)	0
Leukopenia	0	0	9 (7.6)	19 (19.2)	0
Thrombocytopenia	2 (9.5)	4 (4.8)	14 (11.9)	15 (15.2)	0
Lung infection	0	1 (1.2)	3 (2.5)	7 (7.1)	2 (22.2)

AE: adverse event; AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; WBC: white blood cell.

^aNo patients <18 years of age were treated for APL.

Table 4. Summary of grade 5 AEs.

Cohort	Total grade 5 AEs, n (%)	Most common grade 5 AEs	Treatment-related grade 5 AEs
All patients
AML monotherapy (n = 139)	72 (51.8)	Disease progression: n = 31 (22.3%) AML: n = 16 (11.5%) Sepsis: n = 7 (5.0%)	Sepsis: n = 4 (2.9%) Febrile neutropenia: n = 2 (1.4%) Disease progression: n = 1 (0.7%)
AML combination therapy (n = 183)	40 (21.9)	Disease progression: n = 14 (7.7%) Respiratory failure: n = 5 (2.7%) Cardiac arrest, intracranial hemorrhage, pulmonary hemorrhage, respiratory distress, sepsis, and multiple organ dysfunction syndrome: n = 2 (1.1%) each	All n=1 (0.5%): disseminated intravascular coagulation, cardiac arrest; cardiac failure, multiple organ dysfunction syndrome, veno-occlusive liver disease, sepsis, cerebrovascular accident, intracranial hemorrhage, pleural effusion, pulmonary hemorrhage, respiratory failure, and hematoma
APL (n = 9)	2 (22.2)	Disease progression: n = 1 (11.1%) Intracranial hemorrhage: n = 1 (11.1%)	No treatment-related grade 5 AEs were reported
Age <18 years^a
AML monotherapy (n = 21)	7 (33.3)	Disease progression: n=5 (23.8%) Cardiac arrest, chloroma, multiple organ dysfunction syndrome, and respiratory failure: n = 1 (4.8%) each
AML combination therapy (n = 84)	14 (16.7)	Respiratory failure: n = 3 (3.6) Disease progression, sepsis, and pulmonary hemorrhage: n = 2 (2.4%) each
Age ≥18 years
AML monotherapy (n = 118)	65 (55.1)	Disease progression: n = 26 (22.0%) AML: n = 16 (13.6%) Sepsis: n = 7 (5.9%)
AML combination therapy (n = 99)	26 (26.3)	Disease progression: n = 12 (12.1%) Multiple organ dysfunction syndrome and respiratory failure: n = 2 (2.0%) each
APL (n = 9)	2 (22.2)	Disease progression and intracranial hemorrhage: n = 1 (11.1%) each

Only all-causality AEs are reported for age subgroups. AE: adverse event; AML: acute myeloid leukemia; APL: acute promyelocytic leukemia.

^aNo patients <18 years of age were treated for APL.

Table 5. Cases of hepatotoxicity.

Patient	Treatments	Relevant concomitant medications	HSCT details	Hepatotoxicity	Outcome
26-year-old male	GO 17 mg monotherapy	Ursodeoxyxholic acid	N/A	Grade 3 VOD 14 days post-GO	Patient died due to disease progression 23 days post-GO
16-year-old male	GO 5.6 mg + clofarabine, etoposide, cyclophosphamide, methotrexate, hydrocortisone, and cytarabine	Amphotericin B/liposome, fluconazole and voriconazole	N/A	Grade 5 VOD 47 days post-GO	Patient died due to disease progression 66 days post-GO
12-year-old male	GO + cyclophosphamide and methotrexate	Ursodeoxycholic acid	Conditioning regimen with prophylaxis for infection and VOD Busulfan IV intermittent as transplant prophylactic Tacrolimus for anti–graft rejection HSCT 51 days post-GO, complicated by engraftment syndrome and severe vaso-occlusive disease	Grade ≥3 VOD 56 days post-GO and 6 days post-HSCT Received defibrotide treatment	Patient died due to respiratory failure 127 days post-GO
6-year-old female	GO 2.2 mg + etoposide, cytarabine and fludarabine	Ursodeoxycholic acid, and Defibrotide for VOD	HSCT 3 years prior to GO dosing	Grade 3 VOD 7 days post-GO Received defibrotide treatment	Resolved
69-year-old male	GO 17.46 mg monotherapy	Fluconazole and Ursodeoxycholic acid	HSCT 2 years prior to GO dosing Ursodeoxycholic acid for prophylaxis of VOD prior to GO dosing	Drug-induced liver injury 9 days post-GO	Resolved

No patients in the APL group reported hepatotoxicity. All events were considered by the investigator to be related to GO treatment.

APL: acute promyelocytic leukemia; GO: gemtuzumab ozogamicin; HSCT: hematopoietic stem cell transplant; IV: intravenous; N/A: not available; VOD: veno-occlusive disease.

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