LONG-TERM FOLLOW-UP OF SALVAGE TREATMENT FOR RELAPSED AML WITH CLADRIBINE, HIGH DOSE CYTARABINE AND IDARUBICIN (CAI)
(Abstract release date: 05/18/17)
EHA Library. Mayer K. 05/18/17; 182390; PB1676
Karin Mayer
Contributions
Contributions
Abstract
Abstract: PB1676
Type: Publication Only
Background
Despite improving response rates in induction treatment for AML during the last years the outcome for relapsed or refractory AML is still poor. Currently, no standard therapy exists for patients with relapsed AML. Furthermore, CR rates are lower than in newly diagnosed patients and range between 15% and 50%. There is evidence that cladribine (2CdA) has single drug activity in AML as well as an enhancing effect on other cytostatic drugs such as cytarabine (AraC) and thus may help to overcome resistance mechanisms.
Aims
Therefore, testing the combination of 2CdA, AraC and idarubicin (CAI) seems reasonable. Here we present the final analysis from our single-center phase II trial evaluating the safety and efficacy of CAI in relapsed AML patients after a follow-up of 5 years.
Methods
Patients with relapsed AML after at least 6 months of remission and ECOG 0-2 were included. Chemotherapy regime consisted of two courses of 2CdA 5 mg/m²/12 h, d 1-3, AraC 1000 mg/m²/12 h, d1-3 and Idarubicin 8 mg/m²/d, d1-3. After 8 patients, the prolonged duration of neutropenia especially in course 2 prompted us to change the protocol by 1) application of growth factors from day 15 onwards, and 2) omission of idarubicin from the 2nd course. The primary endpoint was the overall remission rate and safety of CAI.
Results
Because of slow recruitment the study was stopped after 20 patients. The median age was 63 years, 40% were female. 19/20 (95%) patients were included in the first relapse after at least 6 months of CR following 1st line therapy for AML. 1/20 (5%) patient was included with a second relapse. In 14/20 patients cytogenetic data at the timing of relapse were available, according to the ELN-risk-group 2017 3/14 (22%) had favourable cytogenetic changes, 9/14 (64%) intermediate and 2/14 (14%) belonged to the adverse cytogenetic group. The performance status was good in most patients (ECOG 0 in 10%, ECOG 1 in 80%), but reduced (ECOG 2) in 2 (20%) patients.
After the first course, CR/CRi was achieved in 60% and PR in 10% of patients. Median duration of neutropenia was 24 days (range 18-41d). The main grade 3 or 4 non-haematologic toxicity was infection seen in 85% of courses. Nausea occurred in 30%, hepatotoxicity, mucositis and diarrhea in 11% of courses. Cardiac or renal toxicities grade 3/4 were not observed. Two patients (10%) died due to infection. Six patients received a second course of CAI/CA. Altogether, 6 patients were refractory. Nine patients (48%) proceeded to allogeneic stem cell transplantation after induction therapy with CAI. Of those, 4 patients are still alive and free of leukemia and one patient died in CR 88 months after salvage-therapy accounting for a 5-year survival rate of 55%.
Conclusion
Combination therapy with CAI in relapsed AML patients is feasible and induces good response rates. Combined with allogeneic stem cell transplantation, long-term survival can be achieved. However, infection rates are a serious complication warranting intensive supportive care.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): Salvage chemotherapy, Relapsed acute myeloid leukemia, Cytarabine, Cladribine
Abstract: PB1676
Type: Publication Only
Background
Despite improving response rates in induction treatment for AML during the last years the outcome for relapsed or refractory AML is still poor. Currently, no standard therapy exists for patients with relapsed AML. Furthermore, CR rates are lower than in newly diagnosed patients and range between 15% and 50%. There is evidence that cladribine (2CdA) has single drug activity in AML as well as an enhancing effect on other cytostatic drugs such as cytarabine (AraC) and thus may help to overcome resistance mechanisms.
Aims
Therefore, testing the combination of 2CdA, AraC and idarubicin (CAI) seems reasonable. Here we present the final analysis from our single-center phase II trial evaluating the safety and efficacy of CAI in relapsed AML patients after a follow-up of 5 years.
Methods
Patients with relapsed AML after at least 6 months of remission and ECOG 0-2 were included. Chemotherapy regime consisted of two courses of 2CdA 5 mg/m²/12 h, d 1-3, AraC 1000 mg/m²/12 h, d1-3 and Idarubicin 8 mg/m²/d, d1-3. After 8 patients, the prolonged duration of neutropenia especially in course 2 prompted us to change the protocol by 1) application of growth factors from day 15 onwards, and 2) omission of idarubicin from the 2nd course. The primary endpoint was the overall remission rate and safety of CAI.
Results
Because of slow recruitment the study was stopped after 20 patients. The median age was 63 years, 40% were female. 19/20 (95%) patients were included in the first relapse after at least 6 months of CR following 1st line therapy for AML. 1/20 (5%) patient was included with a second relapse. In 14/20 patients cytogenetic data at the timing of relapse were available, according to the ELN-risk-group 2017 3/14 (22%) had favourable cytogenetic changes, 9/14 (64%) intermediate and 2/14 (14%) belonged to the adverse cytogenetic group. The performance status was good in most patients (ECOG 0 in 10%, ECOG 1 in 80%), but reduced (ECOG 2) in 2 (20%) patients.
After the first course, CR/CRi was achieved in 60% and PR in 10% of patients. Median duration of neutropenia was 24 days (range 18-41d). The main grade 3 or 4 non-haematologic toxicity was infection seen in 85% of courses. Nausea occurred in 30%, hepatotoxicity, mucositis and diarrhea in 11% of courses. Cardiac or renal toxicities grade 3/4 were not observed. Two patients (10%) died due to infection. Six patients received a second course of CAI/CA. Altogether, 6 patients were refractory. Nine patients (48%) proceeded to allogeneic stem cell transplantation after induction therapy with CAI. Of those, 4 patients are still alive and free of leukemia and one patient died in CR 88 months after salvage-therapy accounting for a 5-year survival rate of 55%.
Conclusion
Combination therapy with CAI in relapsed AML patients is feasible and induces good response rates. Combined with allogeneic stem cell transplantation, long-term survival can be achieved. However, infection rates are a serious complication warranting intensive supportive care.
Session topic: 4. Acute myeloid leukemia - Clinical
Keyword(s): Salvage chemotherapy, Relapsed acute myeloid leukemia, Cytarabine, Cladribine
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