Ivosidenib significantly reduces triazole levels in patients with acute myeloid leukemia and myelodysplastic syndrome.

Background: Ivosidenib is primarily metabolized by CYP3A4; however, it induces CYP450 isozymes, including CYP3A4 and CYP2C9, whereas it inhibits drug transporters, including P-glycoprotein. Patients with acute myeloid leukemia are at risk of invasive fungal infections, and therefore posaconazole and voriconazole are commonly used in this population. Voriconazole is a substrate of CYP2C9, CYP2C19, and CYP3A4; therefore, concomitant ivosidenib may result in decreased serum concentrations.

Dose-Dense Mini-Hyper-CVD, Inotuzumab Ozogamicin and Blinatumomab Achieves Rapid MRD-Negativity in Philadelphia Chromosome-Negative B-cell Acute Lymphoblastic Leukemia.

Background: The combination of low-intensity chemotherapy and inotuzumab ozogamicin (INO), with sequential blinatumomab, is highly effective in older adults with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and in relapsed or refractory B-cell ALL. Earlier, "dose-dense" administration of blinatumomab could lead to earlier and deeper measurable residual disease (MRD) responses and better outcomes.

Patients And Methods: We performed a retrospective analysis of the safety and efficacy of a dose-dense regimen of mini-hyper-CVD (mini-hyperfractionated cyclophosphamide, vincristine, and dexamethasone alternating with mini-methotrexate and cytarabine), INO, and blinatumomab in patients with B-cell ALL.

Incidence of major bleeding in patients with chronic lymphocytic leukemia receiving ibrutinib and therapeutic anticoagulation.

Increased rates of clinically significant bleeding have been reported with ibrutinib, however, limited data is available on the risk when given with concomitant therapeutic anticoagulation. We analyzed the incidence of major bleeding in 64 patient exposures that received ibrutinib with concomitant therapeutic anticoagulation. Major bleeding was observed in 5/64 (8%) patient exposures.

Characteristics and clinical outcomes of patients with acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2).

Acute myeloid leukemia (AML) with inv(3)(q21q26.2)/t(3;3)(q21;q26.2) has a very poor prognosis.

SOHO State of the Art Updates and Next Questions | Hyper-CVAD in 2022: Lessons Learned and New Approaches.

Combination chemotherapy is the mainstay of treatment for acute lymphoblastic leukemia (ALL). The Hyper-CVAD regimen was developed in 1992 at MD Anderson Cancer Center and has since become a standard of care option for adult patients with ALL. Since its conception, a number of modifications have been implemented to customize the regimen for different patient populations and safely incorporate novel therapies without compromising tolerability.

Incidence of adverse effects in patients receiving ponatinib with concomitant azole antifungals.

Ponatinib plus Hyper-CVAD yields a five-year overall survival of 73% in patients with Philadelphia-positive acute lymphoblastic leukemia. Ponatinib dose intensity is associated with increased incidence of adverse effects (AEs), including vascular events. Ponatinib combined with azole antifungals may further increase the risk of AEs due to increased ponatinib exposure.

Phase II Study of Venetoclax Added to Cladribine Plus Low-Dose Cytarabine Alternating With 5-Azacitidine in Older Patients With Newly Diagnosed Acute Myeloid Leukemia.

Purpose: The combination of venetoclax and 5-azacitidine (5-AZA) for older or unfit patients with acute myeloid leukemia (AML) improves remission rates and survival compared with 5-AZA alone. We hypothesized that the addition of venetoclax to cladribine (CLAD)/low-dose araC (low-dose cytarabine [LDAC]) alternating with 5-AZA backbone may further improve outcomes for older patients with newly diagnosed AML.

Methods: This is a phase II study investigating the combination of venetoclax and CLAD/LDAC alternating with venetoclax and 5-AZA in older (≥ 60 years) or unfit patients with newly diagnosed AML.

Urgent cytoreduction for newly diagnosed acute myeloid leukemia patients allows acquisition of pretreatment genomic data and enrollment on investigational clinical trials.

Newly diagnosed acute myeloid leukemia is often deemed a medical emergency, requiring urgent treatment. This is in contradiction with the need for accurate cytogenetic and molecular data, which is not immediately available, to select optimal therapy. We hypothesized that cytoreduction with hydroxyurea or cytarabine would enable urgent disease control and provide a bridge to clinical trial enrollment.

Comparison of Mold Active Triazoles as Primary Antifungal Prophylaxis in Patients With Newly Diagnosed Acute Myeloid Leukemia in the Era of Molecularly Targeted Therapies.

Background: Multiple factors influence the choice of primary antifungal prophylaxis (PAP) in patients with acute myeloid leukemia (AML) undergoing remission induction chemotherapy (RIC) given the recent incorporation of targeted leukemia therapies into these regimens.

Methods: We evaluated the incidence and characteristics of breakthrough invasive fungal infections (bIFI) in 277 adult patients with newly diagnosed AML undergoing RIC with high-intensity, or low-intensity venetoclax-containing therapy. Patients receiving posaconazole (PCZ), voriconazole (VCZ), or isavuconazole (ISA) for > 5 days as PAP during RIC were included.

Clinical and molecular characterization of myeloid sarcoma without medullary leukemia.

Myeloid sarcoma (MS) in the setting of concomitant medullary AML is relatively well described, while much less is known about patients presenting with MS with <20% bone marrow blasts. We conducted a retrospective analysis of 56 patients with MS with <20% marrow blasts seen at MD Anderson between 2005 and 2020. The prevalence of MS without medullary AML was 1.

Ten-day decitabine with venetoclax versus intensive chemotherapy in relapsed or refractory acute myeloid leukemia: A propensity score-matched analysis.

Background: Relapsed/refractory (R/R) acute myeloid leukemia (AML) has poor outcomes. Although lower-intensity venetoclax-containing regimens are standard for older/unfit patients with newly diagnosed AML, it is unknown how such regimens compare with intensive chemotherapy (IC) for R/R AML.

Methods: Outcomes of R/R AML treated with 10-day decitabine and venetoclax (DEC10-VEN) were compared with IC-based regimens including idarubicin with cytarabine, with or without cladribine, clofarabine, or fludarabine, with or without additional agents.

Outcomes of TP53-mutant acute myeloid leukemia with decitabine and venetoclax.

Background: TP53 mutation (TP53 ) confers an adverse prognosis in acute myeloid leukemia (AML). Venetoclax with hypomethylating agents is a current standard for older patients; however, recent reports suggest that TP53 confers resistance to venetoclax. The authors investigated the outcomes of patients with TP53 AML who were treated with a 10-day decitabine and venetoclax (DEC10-VEN) (ClinicalTrials.

Long-term results of low-intensity chemotherapy with clofarabine or cladribine combined with low-dose cytarabine alternating with decitabine in older patients with newly diagnosed acute myeloid leukemia.

The treatment of older patients with newly diagnosed acute myeloid leukemia (AML) using intensive chemotherapy is associated with treatment intolerance and poor survival. We evaluated two new lower-intensity regimens with clofarabine (n = 119) or cladribine (n = 129) combined with low-dose cytarabine (LDAC) alternating with decitabine. We reviewed response rates by subgroup and long term outcomes of 248 patients with newly diagnosed non core-binding-factor AML treated on two clinical trials investigating double nucleoside-analogue therapy (DNT) alternating with HMA from October, 2008 to April, 2018.

Multicenter comparison of high-dose cytarabine-based regimens versus liposomal daunorubicin and cytarabine (CPX-351) in patients with secondary acute myeloid leukemia.

Liposomal daunorubicin/cytarabine (CPX-351) gained FDA approval for secondary AML after demonstrating improved outcomes over daunorubicin and cytarabine (7 + 3). A number of study limitations prompted a comparison of safety/efficacy of CPX-351 against regimens containing a purine analogue and high-dose cytarabine (HIDAC). This retrospective study compared complete response rates with/without count recovery (CR/CRi) between HIDAC-based regimens and CPX-351 in 169 patients with newly diagnosed sAML.

Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia.

Background: Venetoclax (VEN) combined with the hypomethylating agent (HMA) azacitidine improves survival in patients aged ≥75 years with newly diagnosed acute myeloid leukemia (AML). VEN and HMA treatment can result in prolonged and often profound neutropenia, and this warrants antifungal prophylaxis. Azole antifungals inhibit cytochrome P450 3A4, the primary enzyme responsible for VEN metabolism; this results in VEN dose reductions for each concomitant antifungal.

Prognostic value of measurable residual disease after venetoclax and decitabine in acute myeloid leukemia.

Assessment of measurable residual disease (MRD) provides prognostic information in acute myeloid leukemia (AML). However, the utility of MRD with venetoclax-based lower intensity regimens is unknown. We analyzed the prognostic value of achieving a negative MRD in older/"unfit" patients with AML receiving first-line therapy with 10-day decitabine and venetoclax.