Invasive fungal infections in acute myeloid leukemia treated with venetoclax and hypomethylating agents

Aldoss, Ibrahim; Dadwal, Sanjeet; Zhang, Jianying; Tegtmeier, Bernard; Mei, Matthew; Arslan, Shukaib; Malki, Monzr M. Al; Salhotra, Amandeep; Ali, Haris; Aribi, Ahmed; Sandhu, Karamjeet S.; Khaled, Samer K.; Snyder, David S.; Nakamura, Ryotaro; Stein, Anthony S.; Forman, Stephen J.; Marcucci, Guido; Pullarkat, Vinod

doi:10.1182/bloodadvances.2019000930

Cited by 61 publications

(99 citation statements)

References 20 publications

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“…The incidence of invasive fungal infections with venetoclax-based therapies in prospective and retrospective studies using non-azole antifungal prophylaxis (e.g. echinocandin) or no prophylaxis has ranged between 8 and 24% (18,72). Predictors for infections included treatment in the R/R setting and lack of therapy response.…”

Section: Antimicrobial Prophylaxismentioning

confidence: 99%

Venetoclax-Based Combinations in Acute Myeloid Leukemia: Current Evidence and Future Directions

Samra

Konopleva

Isidori³

et al. 2020

Front. Oncol.

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The past decade has witnessed major advances in our understanding of molecular biology, which led to breakthrough novel therapies, importantly including the B-cell lymphoma-2 (BCL-2) inhibitor venetoclax. Notably, venetoclax-based combinations have improved outcomes, including both remission rates and overall survival, of older patients with acute myeloid leukemia (AML) deemed "unfit" for intensive chemotherapy due to age or comorbidities. This has translated into a rapid and widespread use of venetoclax-based combinations in both academic and community-based settings. Other venetoclax-based combinations are being investigated in AML with the ultimate goal of improving cure rates across many subgroups; frontline and relapsed/refractory, in combination with intensive chemotherapy, in the post-transplant setting, or as maintenance strategy. In this article, we summarize the current available data on venetoclax-based combinations. We also highlight areas of unmet medical need, and we offer practical clinical pearls for management of patients receiving such therapy.

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Section: Antimicrobial Prophylaxismentioning

confidence: 99%

Venetoclax-Based Combinations in Acute Myeloid Leukemia: Current Evidence and Future Directions

Samra

Konopleva

Isidori³

et al. 2020

Front. Oncol.

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“…Since approval of venetoclax in 2018 for upfront use in AML, it has gained popularity as a salvage regimen with a handful of published retrospective reports that are delineated in Table 2 (refs. 20,[25][26][27][28][29][30][31][32][33][34] ). We recommend exercising caution while interpreting findings from these reports due to immense heterogeneity in patient population studied (inclusion of relapsed MDS, other myeloid malignancies, prior HMA exposure, post AHSCT), in addition to variations in dose and schedule of treatment regimens utilized either as monotherapy, combination with HMA or low-dose cytarabine.…”

Section: Venetoclax As Salvage Therapy In Amlmentioning

confidence: 99%

Venetoclax-based chemotherapy in acute and chronic myeloid neoplasms: literature survey and practice points

Gangat

Tefferi

2020

Blood Cancer J.

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Venetoclax (VEN), a small-molecule inhibitor of B cell leukemia/lymphoma-2, is now FDA approved (November 2018) for use in acute myeloid leukemia (AML), specific to newly diagnosed elderly or unfit patients, in combination with a hypomethylating agent (HMA; including azacitidine or decitabine) or low-dose cytarabine. A recent phase-3 study compared VEN combined with either azacitidine or placebo, in the aforementioned study population; the complete remission (CR) and CR with incomplete count recovery (CRi) rates were 28.3% and 66.4%, respectively, and an improvement in overall survival was also demonstrated. VEN-based chemotherapy has also shown activity in relapsed/refractory AML (CR/CRi rates of 33–46%), high-risk myelodysplastic syndromes (CR 39% in treatment naïve, 5–14% in HMA failure), and blast-phase myeloproliferative neoplasm (CR 25%); in all instances, an additional fraction of patients met less stringent criteria for overall response. Regardless, venetoclax-induced remissions were often short-lived (less than a year) but long enough to allow some patients transition to allogeneic stem cell transplant. Herein, we review the current literature on the use of VEN-based combination therapy in both acute and chronic myeloid malignancies and also provide an outline of procedures we follow at our institution for drug administration, monitoring of adverse events and dose adjustments.

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“…Our patient exhibited prolonged neutropenia during venetoclax therapy, possibly enhanced by concomitant posaconazole administration 8,12 . It is debatable whether antifungal prophylaxis was necessary, as invasive fungal infections during venetoclax/HMA treatment are rare 13 . Dose reduction by 50% of venetoclax was performed instead of the 75% reduction recommended by the manufacturer and literature, 8,12 with only moderate recovery of neutrophil count.…”

Section: Medication Total Dose (Mg) Daily Dose Daymentioning

confidence: 86%

Venetoclax and decitabine for relapsed paediatric myelodysplastic syndrome‐related acute myeloid leukaemia with complex aberrant karyotype after second stem cell transplantation

Raedler¹,

Heyde²,

Kolokythas³

et al. 2020

Br J Haematol

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Invasive fungal infections in acute myeloid leukemia treated with venetoclax and hypomethylating agents

Abstract: Key Points The incidence of IFIs during VEN-HMA therapy is low, and the used antifungal prophylaxis approach did not influence the risk of IFIs. The risk of IFIs is higher in nonresponders and those who were treated in the r/r AML setting.

Cited by 61 publications

References 20 publications

Venetoclax-Based Combinations in Acute Myeloid Leukemia: Current Evidence and Future Directions

Venetoclax-Based Combinations in Acute Myeloid Leukemia: Current Evidence and Future Directions

Venetoclax-based chemotherapy in acute and chronic myeloid neoplasms: literature survey and practice points

Venetoclax and decitabine for relapsed paediatric myelodysplastic syndrome‐related acute myeloid leukaemia with complex aberrant karyotype after second stem cell transplantation

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