Gemtuzumab Ozogamicin (Mylotarg^®) as Single Agent Treatment for Adult Patients with Acute Myeloid Leukemia (AML).

Strategies the outcome for AML patients involve the use of new agents with reduced toxicity. Gemtuzumab ozogamicin (GO) is an immunoconjugate that has shown controversial activity in AML. It is composed of a humanized anti-CD33 antibody linked to the potent antitumor antibiotic calicheamicin. This agent provides a novel method of drug delivery by using the monoclonal antibody to target CD33⁺ leukemic cells without many of the systemic toxicities associated with traditional chemotherapeutic agents. The therapeutic activity and toxicity profile of GO were assessed in 30 patients from our institution (12 males, 18 females), aged 18 to 74 (median, 63 years), with AML who were either in first (n = 5), second (n = 10), third (n = 12), or fourth line (n = 3) of therapy. The drug was administered either at the dose of 6 mg/m² as a single 2-hour IV infusion on days 1 and 15 (n = 6) or at the dose of 3 mg/m² on days 1, 4 and 7 (n = 24). The overall CR/CRp proportion after GO was 30% (95% CI, 15% – 49%). The CR/CRp proportions were 20%, 30%, and 33% for patients treated in first, second, or further therapeutic line respectively. There was no influence of cytogenetics, antecedents of myelodysplasia, or previous treatment by stem cell transplantation on CR/CRp proportions. Only age (54% in patients < 60 years vs 12% for those ≥ 60 years; p = 0.01) and surprisingly gender (50% in females vs none in males; p = 0.003) influenced CR/CRp proportions. Of the 30 patients, 20 (67%) received the scheduled injections. Reasons for not administering the full dose were progressive disease and drug-induced toxicity. Myelosuppression was universally observed during treatment (93%). Additional severe toxicities that occurred during therapy were: febrile neutropenia and infections (63%), intolerance (10%), liver toxicity (10%). Veno-occlusive disease was observed in one patient. Salvage or consolidation treatment by chemotherapy or donor lymphocyte infusion (in previously transplanted patients) was administered to 16 patients only. CR/CRp proportion raises to 43% after salvage therapy. The duration of previous CR appeared then as of prognostic value for CR achievement (17% for previous CR < 6 months vs 64% for CR ≥ 6 months; p = 0.02). Three patients received allogeneic stem cell transplantation as postremission therapy. Eight of the 13 patients who achieved CR relapsed (median, 4.1 months). After relapse, 3 patients were retreated with GO, of which 2 achieved CR again. The median DFS time was 3 months with a 6–month DFS at 22%. The median overall survival time for all patients was 6.8 months with a 6-month and a 1-year survival rates of 57% and 35% respectively. Age (p = 0.01), duration of previous CR (p = 0.002), and achievement of CR after GO therapy (p = 0.01) were the only factors that impact on outcome in terms of OS. These results suggest that the option of single agent GO therapy is viable in this patient population. Although only observed in 30%, responses were present regardless of the karyotype. However, responses were short warranting additional studies using GO in combination with other drugs or chemotherapy.