Contributions
Abstract: PB1409
Type: Publication Only
Session title: Acute myeloid leukemia - Clinical
Background
Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are two AML subtypes with very poor prognosis. The CLTR0310-301 study showed survival advantages in favour of CPX-351 compared to “7+3” in newly diagnosed t-AML or AML-MRC, 60-75 years old.
Aims
To explore the efficacy of CPX-351 in younger patients in a real-life setting.
Methods
Since September 2019 we treated 9 patients with CPX-351, with a median age of 51 (range 32-59) and ECOG range 0-2. Our cohort consisted in 6 patients with MRC-AML, 2 patients with t-AML and 1 patient with t-AML after a therapy-related myelodysplastic syndrome (t-MDS). 2 patients (both with AML-MRC) harboured FLT3-ITD (Allelic Ratio 0.1), 1 patient IDH1 and 1 patient TP53 mutation. 4 patients had a complex karyotype and 2 patients had received prior treatment with hypomethylating agents (HMA).
Results
All patients underwent induction therapy with intravenous administration of CPX-351 at day 1, 3 and 5 except 1 patient who received just two doses due to pneumonia outbreak. One patient developed a right upper limb lesion, initially with phlebitic appearance and then with necrotic evolution. He eventually died due to severe pneumonia. Eight out of 9 patients were evaluable at the end of treatment. Disease re-evaluation was performed on average 42 days since induction therapy start. Four patients reached a complete remission (CR) and 1 patient a CR with incomplete haematological recovery (CRi), with 63% overall response rate (ORR). One patient showed a partial remission (PR), while 2 patients were refractory. Median days of severe neutropenia (defined as neutrophils lower than 500/uL) were 31. Median days of severe thrombocytopenia (defined as platelets lower than 20.000/uL) were 25. The patient in PR, who was FLT3 mutated, underwent reinduction, with administration of CPX-351 in day 1 and 3, obtaining a CR. Three patients completed both consolidation cycles and underwent bone marrow transplantation. One patient, who was IDH1 mutated, received just one consolidation cycle before transplant and 1 patient was transplanted immediately after induction. A 46 years old patient in CR after induction relapsed after 5 months being off therapy due to a fungal infection whose treatment required a long period of hospitalization to carry out targeted antifungal therapy. Given the CR achieved and the high infectious risk highlighted during induction, the patient did not carry out any consolidation cycle while waiting for transplant. The 2 refractory patients, who both showed complex karyotype and one of them was TP53 mutated, were switched to other regimens.
Conclusion
We found that CPX-351 is active in young patients with t-AML and AML-MRC with a rate of ORR higher than that reported in the pivotal study (63% vs 47%). This improvement be explained by the fact that younger patients better tolerate chemotherapy and its complications. Complex karyotype and TP53 mutation confirmed their role as negative prognostic factors, while better prognosis was observed for FLT3 and IDHs mutated patients although numbers are too small to drive full conclusions. With this therapy we were able to bridge 5 out of 8 (62%) evaluable candidate patients to HSCT. Regarding the safety profile, the most frequent complication was febrile neutropenia (60%), successfully managed with supportive therapy. In conclusion, our results are in line with those reported by other institution real-life data in patients <60 years.
Keyword(s): Acute myeloid leukemia, Age, Secondary, Therapy-related AML
Abstract: PB1409
Type: Publication Only
Session title: Acute myeloid leukemia - Clinical
Background
Therapy-related acute myeloid leukemia (t-AML) and AML with myelodysplasia-related changes (AML-MRC) are two AML subtypes with very poor prognosis. The CLTR0310-301 study showed survival advantages in favour of CPX-351 compared to “7+3” in newly diagnosed t-AML or AML-MRC, 60-75 years old.
Aims
To explore the efficacy of CPX-351 in younger patients in a real-life setting.
Methods
Since September 2019 we treated 9 patients with CPX-351, with a median age of 51 (range 32-59) and ECOG range 0-2. Our cohort consisted in 6 patients with MRC-AML, 2 patients with t-AML and 1 patient with t-AML after a therapy-related myelodysplastic syndrome (t-MDS). 2 patients (both with AML-MRC) harboured FLT3-ITD (Allelic Ratio 0.1), 1 patient IDH1 and 1 patient TP53 mutation. 4 patients had a complex karyotype and 2 patients had received prior treatment with hypomethylating agents (HMA).
Results
All patients underwent induction therapy with intravenous administration of CPX-351 at day 1, 3 and 5 except 1 patient who received just two doses due to pneumonia outbreak. One patient developed a right upper limb lesion, initially with phlebitic appearance and then with necrotic evolution. He eventually died due to severe pneumonia. Eight out of 9 patients were evaluable at the end of treatment. Disease re-evaluation was performed on average 42 days since induction therapy start. Four patients reached a complete remission (CR) and 1 patient a CR with incomplete haematological recovery (CRi), with 63% overall response rate (ORR). One patient showed a partial remission (PR), while 2 patients were refractory. Median days of severe neutropenia (defined as neutrophils lower than 500/uL) were 31. Median days of severe thrombocytopenia (defined as platelets lower than 20.000/uL) were 25. The patient in PR, who was FLT3 mutated, underwent reinduction, with administration of CPX-351 in day 1 and 3, obtaining a CR. Three patients completed both consolidation cycles and underwent bone marrow transplantation. One patient, who was IDH1 mutated, received just one consolidation cycle before transplant and 1 patient was transplanted immediately after induction. A 46 years old patient in CR after induction relapsed after 5 months being off therapy due to a fungal infection whose treatment required a long period of hospitalization to carry out targeted antifungal therapy. Given the CR achieved and the high infectious risk highlighted during induction, the patient did not carry out any consolidation cycle while waiting for transplant. The 2 refractory patients, who both showed complex karyotype and one of them was TP53 mutated, were switched to other regimens.
Conclusion
We found that CPX-351 is active in young patients with t-AML and AML-MRC with a rate of ORR higher than that reported in the pivotal study (63% vs 47%). This improvement be explained by the fact that younger patients better tolerate chemotherapy and its complications. Complex karyotype and TP53 mutation confirmed their role as negative prognostic factors, while better prognosis was observed for FLT3 and IDHs mutated patients although numbers are too small to drive full conclusions. With this therapy we were able to bridge 5 out of 8 (62%) evaluable candidate patients to HSCT. Regarding the safety profile, the most frequent complication was febrile neutropenia (60%), successfully managed with supportive therapy. In conclusion, our results are in line with those reported by other institution real-life data in patients <60 years.
Keyword(s): Acute myeloid leukemia, Age, Secondary, Therapy-related AML