International Journal of Hematology and Oncology
2024, Vol 34, Num 1 Page(s): 075-082
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Real-Life Experience of Dose-Adjusted Venetoclax in Acute Myeloid Leukemia Patients Concomitantly Using Posaconazole for Antifungal Prophylaxis: A Single-Center Experience
Utku ILTAR1, Ece VURAL1, Fadime Nurcan ALHAN1, Sertac VURGUN1, Unal ATAS2, Orhan Kemal YUCEL1, Ozan Salim1, Turgay ULAS3, Mert COSKUN4, Asli TOYLU4, Sibel Berker KARAUZUM4, Levent UNDAR1
1Akdeniz University, Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Antalya, Turkey
2Antalya Training and Research Hospital, Department of Internal Medicine, Division of Hematology, Antalya, Turkey
3Near East University, Faculty of Medicine, Department of Hematology, Antalya, Turkey
4Akdeniz University Faculty of Medicine, Department of Medical Genetics, Antalya, Turkey
Keywords: Acute myeloid leukemia, Hypomethylating agent, Venetoclax, Posaconazole, Dose adjustment
The treatment process in acute myeloid leukemia (AML) often results in prolonged neutropenia, especially in the early period, and this requires antifungal prophylaxis. In the era of venetoclax (VEN), concomitant antifungal prophylaxis has been abandoned because azole antifungals inhibit cytochrome P450 3A4, the primary enzyme responsible for VEN metabolism. If azole antifungal prophylaxis
is used with VEN, the dose of VEN needs to be reduced, but the clinical consequences in this situation are unknown. Limited clinical data exist on outcomes for patients treated with VEN, a hypomethylating agent (HMA), and posaconazole. We retrospectively evaluated our single-center experience on 46 patients, 20 treatment-naive and 26 relapsed/refractory (RR) AML patients. VEN was
used after dose adjustment due to concomitant posaconazole use for antifungal prophylaxis. The median age was 65.5 years (range, 18-78). The median follow-up was 5.5 months (range, 1-25). The overall response rate (ORR) was 60.8%. The incidence of invasive fungal infection was 15.2%. The median OS from venetoclax initiation of all the patients and those with CR/CRi was 6 and 10 months, respectively. After VEN dose reduction due to concomitant posaconazole use, the observed ORR was comparable to the ORR previously reported in the literature without VEN dose reduction and antifungal prophylaxis. However, the OS obtained in our patients was shorter than previously reported in the literature. In addition, the incidence of invasive fungal infections in our patients was not less than that reported in the VEN and HMA studies without antifungal prophylaxis.
Utku ILTAR1, Ece VURAL1, Fadime Nurcan ALHAN1, Sertac VURGUN1, Unal ATAS2, Orhan Kemal YUCEL1, Ozan Salim1, Turgay ULAS3, Mert COSKUN4, Asli TOYLU4, Sibel Berker KARAUZUM4, Levent UNDAR1
1Akdeniz University, Faculty of Medicine, Department of Internal Medicine, Division of Hematology, Antalya, Turkey
2Antalya Training and Research Hospital, Department of Internal Medicine, Division of Hematology, Antalya, Turkey
3Near East University, Faculty of Medicine, Department of Hematology, Antalya, Turkey
4Akdeniz University Faculty of Medicine, Department of Medical Genetics, Antalya, Turkey
Keywords: Acute myeloid leukemia, Hypomethylating agent, Venetoclax, Posaconazole, Dose adjustment
The treatment process in acute myeloid leukemia (AML) often results in prolonged neutropenia, especially in the early period, and this requires antifungal prophylaxis. In the era of venetoclax (VEN), concomitant antifungal prophylaxis has been abandoned because azole antifungals inhibit cytochrome P450 3A4, the primary enzyme responsible for VEN metabolism. If azole antifungal prophylaxis
is used with VEN, the dose of VEN needs to be reduced, but the clinical consequences in this situation are unknown. Limited clinical data exist on outcomes for patients treated with VEN, a hypomethylating agent (HMA), and posaconazole. We retrospectively evaluated our single-center experience on 46 patients, 20 treatment-naive and 26 relapsed/refractory (RR) AML patients. VEN was
used after dose adjustment due to concomitant posaconazole use for antifungal prophylaxis. The median age was 65.5 years (range, 18-78). The median follow-up was 5.5 months (range, 1-25). The overall response rate (ORR) was 60.8%. The incidence of invasive fungal infection was 15.2%. The median OS from venetoclax initiation of all the patients and those with CR/CRi was 6 and 10 months, respectively. After VEN dose reduction due to concomitant posaconazole use, the observed ORR was comparable to the ORR previously reported in the literature without VEN dose reduction and antifungal prophylaxis. However, the OS obtained in our patients was shorter than previously reported in the literature. In addition, the incidence of invasive fungal infections in our patients was not less than that reported in the VEN and HMA studies without antifungal prophylaxis.
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