High Dose Cytarabine, Clofarabine and Gemtuzumab Ozogamicin (CLAC-MYL) in Relapsed or Refractory AML Patients.

Abstract 1060

Poster Board I-82

Clofarabine has been shown to be effective in AML patients, either as single agent or, mainly, in association with intermediate dose cytarabine. On the basis of these reports, we conducted a preliminary study combining clofarabine, intermediate dose cytarabine and gemtuzumab ozogamicin (Mylotarg) in AML patients who relapsed or failed to respond to at least two induction therapies.

We treated 20 patients affected by relapsed/refractory AML with a regimen including clofarabine at 22,5 mg/m² daily on days 1-5, followed after three hours by cytarabine at 1 gr/m² daily on days 1-5, with the addition of gemtuzumab ozogamicin 6 mg/m² on day 6 (CLAC-Myl). Six patients received a further consolidation cycle with clofarabine at 22,5 mg/m² and cytarabine at 1 gr/m² day 1-4.

Among the twenty patients, six were in first relapse, six in second relapse, eight with resistant disease. The mean age was 52 years (range 33-68 years), the white blood count at the accrual was 31.500 mcc (range 2140-153.000). 10/20 (50%) patients achieved a complete remission, 1/20 a partial response, 7/20 had resistant disease, 2/20 died of complications during the aplastic phase (a case of multiorgan failure an a septic shock caused by Pseudomonas Aeruginosa).

The most frequent non hematologic adverse events were vomiting, diarrhea, transient liver toxicity (2/20 grade 3-4), febrile neutropenia (7/20), infections microbiologically documented (2/20 Pseudomonas Aeruginosa sepsis).

Comparing with other salvage strategies, in this small cohort of patients we did not observe a significant delay in bone marrow recovery (median time to ANC recovery 31.5 days), except in a patient (female, 34 years old, relapsed after ABMT) that experienced an unexpected, irreversible aplasia after the consolidation course, complicated by an unusual HHV6 reactivation.

Among the ten responding patients, three underwent allogeneic bone marrow transplantation, one patient still in CR after 7 months died for complications of an acute myocardial infaction occurred during the consolidation course, one relapsed after 6 months, and five not eligible for transplant procedures are still in complete remission with a median follow up of 6 months.

These very preliminary results suggest that the CLAC-Myl regimen is effective in this particularly poor prognosis category of patients, with safety data consistent with previously reported salvage therapies. Further studies are warranted.