How I Treat MDS/AML: Individualizing Therapy Based on Disease Biology, Patient Fitness, Molecular Features, and Treatment Goals
In the Clinic . . .
Consider the following patient cases encountered in my clinic.
Case 1: Secondary AML With Adverse-Risk Genetics
A 65-year-old male presents with pancytopenia identified by their primary care physician at the time of an upper respiratory infection. Past medical history includes hypertension, obesity, and a smoking history. Eastern Cooperative Oncology Group (ECOG) performance status (PS) is 1. Laboratory values include a white blood cell (WBC) count of 2500 cells/μL, absolute neutrophil count (ANC) of 900 cells/μL, a hemoglobin of 8.5 g/dL, and a platelet count of 65,000/μL. A bone marrow biopsy shows 28% blasts with a background of underlying trilineage dysplasia. Molecular profiling reveals TET2, ASXL1, and U2AF1 mutations.
Although the patient has relative fitness for intensive chemotherapy, he also has underlying myelodysplastic syndrome (MDS)–associated changes and adverse-risk genetics per the European LeukemiaNet (ELN) 2022 criteria.1 For this type of patient, I would prioritize a hypomethylating agent (HMA) + venetoclax regimen, followed by a stem cell transplant (SCT) in first complete remission (CR1).
Case 2: Proliferative Monocytic AML
A 65-year-old male presents with petechiae and bruising. He also has a history of hypertension, obesity, and smoking, plus an ECOG PS of 1. Laboratory findings include a WBC count of 52,000 cells/μL, circulating blasts, a hemoglobin of 8.5 g/dL, and a platelet count of 35,000/μL. A bone marrow biopsy shows 55% blasts with monocytic features. Molecular profiling reveals deletion (20q) and mutations in ASXL1 and NRAS.
Although there are commonalities between this patient and the prior one, this patient has a proliferative monocytic leukemia with an NRAS mutation. This patient is classified as ELN 2022 intermediate risk, and notably NRAS mutations are not adverse risk when treated with intensive chemotherapy regimens. However, when treated with lower-intensity regimens including venetoclax, both RAS mutations and monocytic disease biology have been associated with primary and secondary resistance. Thus intensive chemotherapy would be my preferred treatment option here, followed by an SCT in CR1.
Case 3: NPM1/FLT3-ITD AML
A 55-year-old female presents with progressive fatigue and bruising; she has no significant past medical history and has an ECOG PS of 1. Laboratory findings include a WBC count of 25,000 cells/μL, a hemoglobin of 8.5 g/dL, and a platelet count of 25,000/μL. A bone marrow biopsy shows 55% blasts with monocytic features. Molecular profiling reveals NPM1 and FLT3-internal tandem duplication (ITD) mutations.
Given the patient’s de novo acute myeloid leukemia (AML) phenotype and the presence of the targetable FLT3 mutation, the treatment choice here is intensive chemotherapy + a FLT3 inhibitor. Both midostaurin and quizartinib are approved as frontline FLT3 inhibitors in combination with intensive chemotherapy. NPM1 and FLT3 should be monitored during treatment, and an SCT in CR1 is indicated if the patient does not attain measurable residual disease (MRD)–negative status by both NPM1 and FLT3-ITD.
Case 4: AML in an Older Patient
A 78-year-old female presents with progressive fatigue and bruising. Past medical history includes hypertension, type 2 diabetes, and osteoarthritis, all well controlled. Laboratory findings include a WBC count of 2500 cells/μL, a hemoglobin of 8.2 g/dL, and a platelet count of 55,000/μL. A bone marrow biopsy shows 28% blasts and molecular profiling reveals 2 DDX41 mutations (DDX41 p.D140fs at 45% variant allele frequency [VAF] and p.R525H at 5% VAF).
In this patient, the primary molecular feature affecting the treatment decision is the lack of an IDH1 mutation, which would favor the use of azacitidine + ivosidenib.2 The patient’s age will preclude use of SCT, so the optimal treatment will be an HMA + venetoclax regimen that is continued for as long as she benefits. Of note, the presence of a DDX41 mutation at near-heterozygous frequency (~50% VAF) indicates that this patient likely has a hereditary hematologic malignancy related to inheritance of a germline DDX41 mutation. Patients with DDX41 mutations can do quite well with an HMA + venetoclax–based therapy, and are considered ELN 2024 favorable risk.
The Common Thread: Individualizing Therapy Based on Disease Biology, Patient Fitness, Molecular Features, and Treatment Goals
Why do these patients require different treatment approaches? Selection of initial treatment for patients with AML requires a nuanced consideration of disease-related, treatment-related, and patient-related factors. Patient fitness is a primary consideration, and eligibility for intensive induction therapy is still the first dichotomous factor for initial treatment selection in the current National Comprehensive Cancer Network (NCCN) clinical guidelines.2 However, treatment decisions are increasingly individualized based on disease risk, the presence of molecular alterations, and patient-related factors.
Conventionally, use of allogeneic SCT in patients with AML was limited to patients receiving intensive induction chemotherapy. However, today patients can proceed to SCT after a lower-intensity regimen, typically an HMA + venetoclax. In fact, recent evidence from the PARADIGM trial indicates that some patients, primarily those with adverse-risk AML, may be more likely to successfully proceed to SCT after an HMA + venetoclax regimen than after intensive chemotherapy.3 However, this trial excluded some patients, including those with core binding factor (CBF)-AML, FLT3-mutated AML, and younger adults with NPM1 mutations, where the curative potential of intensive chemotherapy is well recognized. Therefore, determination of the optimal induction therapy approach in different clinical scenarios remains an important topic of ongoing discussion.
MRD testing is also gaining an increasing role in monitoring treatment responses and guiding therapeutic decisions. The presence of MRD after induction therapy is associated with an increased risk of relapse.4,5 Accordingly, patients with NPM1-, CBFB::MYH11-, or RUNX1::RUNX1T1-mutated AML with confirmed MRD positivity after induction and/or consolidation therapy should be considered for SCT or other further therapies. MRD positivity can also guide the use of post-SCT maintenance therapy in patients with FLT3-mutated AML.
AML Overview
AML is a rare, aggressive, hematologic malignancy characterized by clonal expansion of immature myeloid precursors in the peripheral blood and bone marrow leading to myelosuppression and bone marrow failure.6 AML will be diagnosed in approximately 22,720 individuals in the United States in 2026, accounting for 1.1% of new cancer cases. An estimated 11,500 individuals will die from AML in 2026, representing 1.8% of cancer deaths.7
AML is more common in men than in women, with age-adjusted rates of 5.2 vs 3.7 cases per 100,000 persons.7 Older adults are more likely to be diagnosed with AML; the median age at diagnosis is 70 years. However, younger adults can also be affected, and nearly one-quarter of diagnoses (22.7%) occur in patients younger than 55 years.
Most AML cases are de novo, arising in the absence of known precipitating factors. The remaining 10% to 20% of diagnoses are encompassed in the heterogeneous category of secondary AML (sAML); these include cases of AML occurring after a prior myeloid disease such as MDS or myeloproliferative neoplasm, AML developing subsequent to cytotoxic chemotherapy or radiation for another disease (treatment-related AML), and AML in patients with germline predisposition.8 sAML is associated with a worse prognosis than de novo AML, although patient age, comorbidities, cytotoxic treatment history, and molecular characteristics all influence prognosis.
AML Treatment Framework
Establishing the Diagnosis and Disease Biology
Criteria for the diagnosis and classification of AML have changed over the years as more became understood about its pathologic and molecular features. In 2022, 2 different classification systems—the World Health Organization (WHO) criteria and the International Consensus Criteria—were published, classifying myeloid diseases and subtypes based on molecular findings, pathologic features, prior cytotoxic exposure, and genetic predisposition.9,10
According to the 2022 WHO criteria, a diagnosis of AML requires at least 20% myeloid blasts in the bone marrow except for the presence of defining genetic abnormalities, for which there is no minimum blast threshold.9,10 The accurate classification of AML requires morphologic analysis, immunophenotyping including immunohistochemistry and flow cytometry, and molecular analyses including cytogenetics, fluorescence in situ hybridization, and mutation sequencing.2 In order to individualize initial therapy appropriately, molecular and cytogenetic analysis should be expedited to obtain results for immediately actionable mutations or chromosomal abnormalities, with results ideally made available within 1 week.2
Assessing the Patient and Defining Treatment Intent
The evaluation for patients with AML includes determination of the ELN 2022 risk category, which stratifies patients based on the risk of recurrence following intensive induction chemotherapy (Figure 1).1 Adverse-risk AML per the ELN 2022 is significantly more common in older adults vs younger adults and is more common in patients with sAML.11
Consideration of patient-related factors, including fitness, PS, goals of care, patient preferences, and social support, are also keys to individualizing AML treatment.12 This is particularly relevant as additional treatment options are introduced.
Choosing Initial Therapy
The treatment landscape for AML has changed dramatically in recent years, with 8 new agents introduced in newly diagnosed AML alone in the past 10 years (Figure 2).13 With numerous options available, frontline treatment is selected bases on multiple factors, including disease characteristics, treatment factors, and patient-related factors and preferences.2 Key determinants include the patient’s fitness driven by age and PS and the molecular profile of the disease, which informs the ELN genetic risk classification and guides the use of targeted therapies.1
Intensive Chemotherapy: The Clear Choice for Some Patients
Conventionally, intensive induction chemotherapy has been the standard approach for all eligible patients with AML, and it remains the clear choice for selected patients (Figure 3). For example, in younger patients with favorable-risk AML by cytogenetics (CBF-AML) or by molecular mutation profile, intensive chemotherapy is the appropriate strategy as this offers a curative approach.
The standard 7+3 regimen consisting of cytarabine continuous infusion for 7 days with an anthracycline, typically daunorubicin or idarubicin, administered daily for 3 days is frequently used as a standard induction therapy.2 Gemtuzumab ozogamicin can be added to 7+3 for patients with CD33-positive AML, and is most beneficial in patients with CBF leukemias (t[8;21] or inv[16]). An FLT3 inhibitor is added to 7+3 for patients with FLT3-mutated AML. In terms of the FLT3 inhibitors available, midostaurin can be used for patients with FLT3-ITD or tyrosine kinase domain mutations, whereas the second-generation FLT3 inhibitor quizartinib should be used only for patients with FLT3-ITD mutations.
Intensive Induction for Patients With sAML
As the population is aging, and as the number of individuals exposed to cytotoxic agents for other medical conditions is increasing, the incidence of sAML is also increasing.14 Outcomes for patients with sAML are poor; patients do not tend to have targetable alterations, and many novel agents have limited efficacy in sAML.
For patients with sAML who are eligible for intensive chemotherapy, the preferred induction therapy for adults is CPX-351, a dual-drug formulation of liposomal cytarabine and daunorubicin that has demonstrated improved response rates and overall survival in patients in this population.2
HMA + Venetoclax as a Lower-Intensity Induction Therapy
Approximately one-half of patients with AML are ineligible for intensive induction therapy owing to poor PS, comorbidity, and/or older age.15 Prior to the introduction of an HMA + venetoclax approach, there were limited treatment options for these patients, and prognosis with an HMA or low-dose cytarabine alone was quite poor. However, the introduction of the HMA + venetoclax combination approach has changed the AML treatment paradigm over the past 5 to 10 years, and it is now the standard treatment for patients who are not candidates for, or who decline, intensive chemotherapy (Figure 3).2
Today, 3 HMAs are available for use in combination with venetoclax: the parenterally administered azacitidine and decitabine, and the oral formulation of decitabine and cedazuridine.16-18 Each of these agents has been evaluated in combination with venetoclax and is an option for patients with newly diagnosed AML (Figures 4 and 5).19-23
Early Evidence for HMA + Venetoclax
The US Food and Drug Administration initially granted accelerated approval for the use of azacitidine or decitabine + venetoclax based on response rates demonstrated in the open-label, nonrandomized study M14-358 in patients with newly diagnosed AML who were at least 75 years of age or had comorbidities precluding the use of intensive induction chemotherapy.19 In that trial, venetoclax + either azacitidine or decitabine was associated with a complete remission (CR) or CR with incomplete blood count recovery (CRi) of 67%. The median overall survival (OS) was 17.5 months.
VIALE-A: Azacitidine + Venetoclax
These findings provided a rationale for the randomized, phase 3 VIALE-A trial, which compared azacitidine + venetoclax against azacitidine + placebo in 431 patients with newly diagnosed AML who were at least 75 years of age or otherwise ineligible for intensive induction chemotherapy.20,21 In that trial, azacitidine + venetoclax was associated with a significant improvement over azacitidine + placebo in OS (14.7 vs 9.6 months; hazard ratio [HR], 0.58; 95% CI, 0.52-0.85; P<.001) and an improvement in the composite CR rate, including CR and CRi (66.4% vs 28.3%; P<.001).
Adverse events (AEs) in VIALE-A included nausea, reported in 44% of patients receiving azacitidine + venetoclax and 35% of patients receiving azacitidine + placebo, and grade 3 or higher thrombocytopenia (45% vs 38%), neutropenia (42% vs 28%), and febrile neutropenia (42% vs 19%). The rate of any-grade infections was 84% and 67%, respectively.
ASCERTAIN-V: Oral Decitabine and Cedazuridine + Venetoclax
More recently, results were reported from the phase 1/2 open-label, multicenter ASCERTAIN-V trial evaluating the all-oral regimen of decitabine and cedazuridine + venetoclax in patients with AML who were 75 years of age or older or otherwise ineligible for intensive chemotherapy.22 Decitabine and cedazuridine, available in a fixed-dose formulation, has been shown to have a pharmacokinetic exposure equivalent to that of intravenous decitabine.23
The ASCERTAIN-V trial enrolled 189 patients across its phase 1 (n=30), phase 2a (n=58), and phase 2b (n=101) portions. Following the observation of myelosuppression in phase 1, the phase 2b study used early bone marrow assessments to help mitigate myelosuppression through individualized dose modifications. Blast reductions and the timing of count recovery were used to guide the subsequent dosing schedule.22 Implementation of the early bone marrow assessment was associated with a trend toward reduced dosing of venetoclax over time and subsequent reductions in decitabine and cedazuridine over time. No drug-drug interactions between decitabine and cedazuridine and venetoclax were observed.
In the pivotal phase 2b trial, oral decitabine and cedazuridine + venetoclax was associated with a CR rate of 47%, a CR + CRi rate of 63%, and a median OS of 15.5 months. The median OS improved over time in the trial, which investigators attributed to the implementation of individualized dose and schedule changes to mitigate myelosuppression.
In the phase 2b study, serious AEs (SAEs) occurred in 84% of patients overall and in 62% of patients with a response in cycle 1 or 2. Common grade 3 or higher AEs included anemia (30%), neutropenia (26%), and febrile neutropenia (25%). The 30-day and 60-day mortality rates were 3% and 10%, respectively.
Considerations for Patients With IDH1-Mutated AML
Mutations in IDH1 occur in approximately 10% of patients with AML.21 For patients receiving intensive chemotherapy, IDH1 inhibitors are currently not added to induction therapy. A large randomized study of intensive chemotherapy +/- ivosidenib should have a report out within the year. However, for patients receiving lower-intensity induction therapy, the presence of an IDH1 mutation is considered in the treatment decision, as there are 2 approved standard-of-care combinations for this genomically defined subset.2
In the Clinic…
Data from the PARADIGM trial suggest that just because a patient can tolerate intensive chemotherapy does not mean that intensive chemotherapy is necessarily the best induction regimen for them. Some patients may be able to bridge to transplant with an HMA + venetoclax, allowing them to forgo the toxicity and burden of intensive chemotherapy. Moreover, according to the PARADIGM trial, some patients may in fact be more likely to proceed to SCT after an HMA + venetoclax than with intensive chemotherapy.
As a result, a key question in AML management today is who should optimally receive an HMA + venetoclax and who should receive intensive chemotherapy. Use of the HMA + venetoclax approach is increasingly being utilized in the real world in patients who could tolerate intensive chemotherapy. It is essential that in younger, fitter patients, an HMA + venetoclax is used as a bridge to remission to proceed to a curative transplant. In contrast, for older patients who are not eligible for SCT, an HMA + venetoclax can be continued indefinitely, as long as the therapy is beneficial.
The VIALE-A trial included patients with IDH1 and IDH2 mutations. Subset analyses reported particularly favorable outcomes with azacitidine + venetoclax in patients with IDH2 mutations.24 Azacitidine + venetoclax does remain a Category 1–recommended option in NCCN guidelines for patients with IDH1-mutated AML.2
The other Category 1 recommendation for patients with IDH1-mutated AML is the combination of the IDH1 inhibitor ivosidenib + azacitidine. In the randomized, phase 3 AGILE trial, ivosidenib + azacitidine was associated with significant improvements over placebo + azacitidine in event-free survival (EFS; 12-month EFS rate, 37% vs 12%; HR, 0.33; 95% CI, 0.16-0.69; P=.002) and in OS (24.0 vs 7.9 months; HR, 0.44; 95% CI, 0.27-0.73; P=.001).25
Common grade 3 or higher AE rates were febrile neutropenia (reported in 28% of patients receiving ivosidenib + azacitidine and 34% receiving placebo + azacitidine) and neutropenia (27% vs 16%). Rates of any-grade infection were 28% and 49%, respectively; differentiation syndrome occurred in 14% and 8% of patients, respectively.
Lower-Intensity Therapy as a Bridge to Allogeneic SCT: A New PARADIGM in AML?
Conventionally, patients intending to proceed to potentially curative allogeneic SCT receive intensive chemotherapy as induction therapy for AML. However, the introduction of reduced intensity conditioning regimens has allowed for consideration of SCT in a wider patient population. There are also significant downsides to intensive chemotherapy in terms of toxicity and its requirements for extended hospitalizations. Moreover, there is a need for more effective induction therapy for patients with adverse-risk genetic factors such as MDS-associated mutations (eg, ASXL1, splicing factor mutations), complex cytogenetics, and TP53 mutations.
Retrospective and real-world data have shown that patients can successfully proceed to allogeneic SCT following induction therapy with an HMA + venetoclax.26,27 However, data prospectively comparing an HMA + venetoclax against intensive chemotherapy were lacking, until the randomized, phase 2 PARADIGM trial compared the 2 approaches in patients with AML eligible for intensive chemotherapy (Table).3
In the randomized, phase 2 PARADIGM trial, 172 patients with newly diagnosed AML who were eligible for intensive chemotherapy were randomly assigned to azacitidine + venetoclax (n=86) or intensive chemotherapy (n=86).3 The median age of enrolled patients was 64 years; 72% of patients had adverse-risk AML according to the ELN 2022 classification. The trial excluded patients with CBF-AML, FLT3 mutations, and patients with NPM1 mutations who were younger than age 60.
After a median follow-up of 21.9 months, azacitidine + venetoclax was associated with a significant improvement over intensive chemotherapy in EFS (14.5 vs 6.2 months; HR, 0.57; 95% CI, 0.39-0.84; P=.002) and an improvement in the percentage of patients proceeding to allogeneic SCT (68% vs 40%). In the safety analysis, azacitidine + venetoclax was associated with reductions over intensive chemotherapy in rates of grade 3 or higher infection (28% vs 41%) and grade 3 or higher hemorrhage (2% vs 12%).
MRD for Monitoring Response to Therapy
Patients receiving intensive chemotherapy should be monitored for MRD, which detects the presence of leukemic cells more sensitively than morphologic methods.2 MRD positivity is associated with a higher risk of relapse, even in those with favorable risk features such as CBF or an NPM1 mutation.4,5
The most common methods for assessing MRD are quantitative assays such as real-time quantitative PCR (RQ-PCR) and multicolor flow cytometry to detect specific MRD immunophenotypes. Optimally, the initial MRD assessment should be conducted on a dedicated bone marrow aspirate pull.2 After an MRD-negative remission in the bone marrow is attained, MRD can be assessed in peripheral blood by monitoring for the presence of PML::RAR alpha, NPM1, CBFB::MYH11, and RUNX1T1.
In the Clinic…
In patients who are not eligible for SCT, an HMA + venetoclax regimen is administered as long as the regimen is effective and tolerable. Some patients in my practice have been on these regimens for multiple years, which speaks to the potential long-term tolerability of these regimens.
The availability of an all-oral HMA + venetoclax regimen with the use of oral decitabine and cedazuridine is an important option for patients, as this reduces the need for intravenous therapies, and the time and resources involved, while preserving therapeutic efficacy.
It has been reported that among older adults with AML receiving azacitidine- or venetoclax-based regimens, approximately 42% of their days after the diagnosis are spent at an oncology/infusion clinic or an emergency department with the median duration of infusion visits being 194 minutes.31 If we as
physicians can help patients have more good days at home, and spend less time at infusion centers, that will help improve patients’ quality of life.
NCCN guidelines recommend RQ-PCR for detecting PML::RAR alpha, NPM1, CBFB::MYH11, and RUNX1::RUNX1T1, and a next-generation sequencing–based targeted deep-sequencing assay to detect FLT3-ITD. The threshold of detection should be considered, as these vary based on the technique used and the AML subgroup.
For patients with NPM1-mutated AML, CBFB::MYH11, and RUNX1:RUNX1T1 AML, MRD assessment should be performed after 2 cycles of intensive chemotherapy and every 6 to 12 weeks for 24 months. For patients receiving venetoclax-based lower-intensity regimens, MRD negativity may take longer, including up to 4 to 6 cycles of therapy.
In patients with NPM1-mutated AML receiving venetoclax-based lower-intensity therapy, NPM1 MRD is strongly prognostic.28 Accordingly, NPM1 monitoring by RQ-PCR should be performed every 6 to 12 weeks using bone marrow or peripheral blood in patients receiving venetoclax-based therapy.2 In patients with NPM1-mutated, CBFB::MYH11, and RUNX1::RUNX1T1-mutated AML, the presence of persistently positive MRD after induction and/or consolidation warrants consideration of alternative therapies such as allogeneic SCT or a clinical trial.2 Postinduction MRD positivity has also been shown to identify patients with NPM1-mutated AML who obtain a significant OS benefit from allogeneic SCT in first remission.29
Looking ahead, triplet therapy incorporating an HMA or low-dose cytarabine, venetoclax, and a targeted therapy (directed against FLT3, IDH, or menin) is emerging as potential advancement.30 Triplets are associated with an increased risk of myelosuppression, and triplet therapy will likely require careful selection, particularly in older patients, and proactive use of dose adjustments.
Dose Modification and Practical Management: Managing HMA + Venetoclax
Proactive monitoring, including the use of early bone marrow assessments, to guide use of dose and schedule adjustments are critical for optimizing the use of an HMA + venetoclax in practice.19 Patients may require extended treatment cycles (5 to 6 weeks) and may also require granulocyte colony-stimulating factor (G-CSF) support to minimize periods of neutropenia. These proactive approaches allow the patient to maximize time on therapy and minimize toxicity.
For patients receiving oral decitabine and cedazuridine + venetoclax, an algorithm for managing dosing based on early bone marrow assessments at the end of cycle 1 has been proposed (Figure 5). The recommended dosage of decitabine and cedazuridine in combination with venetoclax is 1 tablet once daily on days 1 to 5 each cycle. I tend to administer venetoclax for 21 days in the first cycle, then do a bone marrow assessment at around days 21 to 28. This will often reveal a blast reduction (<5%), in which case the treatment should be held in order for counts to recover. The timing of count recovery guides the starting schedule for subsequent cycles.
I sometimes find that, after several cycles of oral decitabine and cedazuridine + venetoclax, platelet counts are not recovering to the same extent, or patients are requiring more G-CSF support to reach sustained neutrophil counts. In these patients, I will reduce the number of days that patients receive each agent. Many of my patients who have been receiving the all-oral regimen for a year or longer receive decitabine and cedazuridine for 3 days per cycle rather than 5 days, and the duration of venetoclax is reduced to 14 days per cycle. However, the specific schedules vary across individual patients.
Back to the Clinic . . .
Let’s revisit our initial cases and consider the factors that influence treatment decisions in each of these scenarios. For younger patients who are eligible for intensive chemotherapy, intensive chemotherapy followed by SCT in first remission is the preferred therapy. This includes the patient described with proliferative monocytic AML with a RAS mutation.
For a younger patient with NPM1/FLT3-mutated AML, the treatment choice would also be intensive chemotherapy. Although the PARADIGM trial demonstrated superior efficacy with an HMA + venetoclax compared with intensive chemotherapy in fit patients with newly diagnosed AML, the trial excluded patients younger than age 60 with NPM1 mutations and all patients with FLT3-mutated AML.
Thus the findings are not broadly applicable to the fit AML population. Conversely, the PARADIGM trial does suggest that an HMA + venetoclax followed by allogeneic SCT in first remission could be a consideration for patients with adverse-risk AML and may increase the likelihood of proceeding to SCT.
An HMA + venetoclax remains the standard of care for patients not eligible for intensive induction therapy. Three HMAs are now available for use in combination with venetoclax: the parenterally administered azacitidine and decitabine, and the oral formulation of decitabine and cedazuridine. The oral formulation of decitabine and cedazuridine provides the distinct advantages of reducing the need for intravenous therapies, and the time and resources involved, while preserving therapeutic efficacy. Appropriate mitigation and management of toxicities, including the use of dose and schedule adjustments and supportive care, maximizes the therapeutic benefit of an HMA + venetoclax regimens. Looking ahead, triplet regimens may provide additional more effective induction options in the future.
Disclosures
Dr DiNardo has received research support (funds directly to the institution) from AbbVie, Astex, Auron Therapeutics, Bristol-Myers Squibb, BeiGene, Ellipses Pharma, Jazz, Kura, PMV, Remix, Rigel, Servier, Schrödinger, SillaJen, and SystImmune; and is a consultant for and has served on the advisory boards of (all approved and within institutional COI policy limits) AbbVie, Astellas, AstraZeneca, BeiGene, Bristol-Myers Squibb, Ellipses Pharma, Genentech, Genmab, GlaxoSmithKline, Molecular Partners, Rigel, Ryvu, Schrödinger, Servier, Solu, and Syndax.
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