1.Evaluation of gemtuzumab ozogamycin associated sinusoidal obstructive syndrome: Findings from an academic pharmacovigilance program review and a pharmaceutical sponsored registry.
Magwood-Golston JS1, Kessler S2, Bennett CL2. Leuk Res. 2016 May;44:61-4. doi: 10.1016/j.leukres.2016.03.004. Epub 2016 Mar 16.
BACKGROUND: In 2000, the Food and Drug Administration (FDA) approved gemtuzumab ozogamycin for monotherapy for older patients with relapsed AML. A 0.9% rate of hepatic sinusoidal obstructive syndrome (SOS) was noted in licensing trials. In 2001, FDA received reports of 14 GO-associated SOS cases from MD Anderson Cancer Center. A State of South Carolina/National Cancer Institute funded pharmacovigilance program and a manufacturer sponsored registry independently evaluated this concern.
2.Defining the dose of gemtuzumab ozogamicin in combination with induction chemotherapy in acute myeloid leukemia: a comparison of 3mg/m2 with 6mg/m2 in the NCRI AML17 trial.
Burnett A1, Cavenagh J2, Russell N3, Hills R4, Kell J5, Jones G6, Nielsen OJ7, Khwaja A8, Thomas I4, Clark R9. Haematologica. 2016 Feb 26. pii: haematol.2016.141937. [Epub ahead of print]
A recent source data meta-analysis of randomised trials in adults assessing the immunoconjugate, gemtuzumab ozogamicin combined with standard chemotherapy in acute myeloid leukaemia showed a significant survival benefit in patients without an adverse karyotype. It is not clear whether the optimal dose should be 3mg/m2 or 6mg/m2. In this study we randomised 788 patients to a single dose of gemtuzumab ozogamicin 3mg/m2 or 6mg/m2 with the first course of induction therapy. We found that the rate of complete remission was higher with 3mg/m2 (82% vs 76%;odds ratio 1.46 (1.04-2.06) p=0.03), but this was balanced by a higher rate of complete remission with incomplete peripheral blood count recovery in the 6mg/m2 treatment (10% vs 7%) resulting in similar overall response rate (89% vs 86%;hazard ratio 1.34 (0.88-2.04) p=0.17). Overall, relapse and survival at 4 years were not different between the arms (46% vs 54%; hazard ratio 1.17 (0.94-1.45),p=0.
3.Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy.
Hütter-Krönke ML1, Benner A2, Döhner K1, Krauter J3, Weber D1, Moessner M1, Köhne CH4, Horst HA5, Schmidt-Wolf IG6, Rummel M7, Götze K8, Koller E9, Petzer AL10, Salwender H11, Fiedler W12, Kirchen H13, Haase D14, Kremers S15, Theobald M16, Matzdorff AC17, Haematologica. 2016 Apr 1. pii: haematol.2015.141622. [Epub ahead of print]
Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3mg/m2; intravenously on day 1), all-trans retinoic acid (45 mg/m2; per orally on days 4-6 and 15 mg/m2; orally on days 7-28), high-dose cytarabine (3 g/m2/12 h intravenously on days 1-3) and mitoxantrone (12 mg/m2 intravenously on days 2-3) in 93 patients aged 18 to 60 years refractory to one cycle of induction therapy. Primary endpoint of the study was response to therapy; secondary endpoints included evaluation of toxicities, in particular rate of sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Complete remission or complete remission with incomplete blood count recovery was achieved in 47 (51%) and partial remission in 10 (11%) patients resulting in an overall response rate of 61.5%; 33 (35.5%) patients had refractory disease and 3 patients (3%) died.
