Gustavo Rivero, MD, is the director of translational research for myeloid disorders at Tampa General Hospital Cancer Institute in Florida and an associate professor of hematology/oncology.

David Swoboda, MD, is the clinical director of leukemia at Tampa General Hospital Cancer Institute and an assistant professor at the University of South Florida Morsani College of Medicine in Tampa.

In November 2024, the FDA approved the first-in-class menin inhibitor revumenib (Revuforj; Syndax) for the treatment of patients with relapsed/ refractory leukemia with 

 translocations, including myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and mixed phenotype acute leukemia (MPAL). The approval is a critical step in understanding epigenetic leukemia vulnerabilities.

-mutated AML and AML, ALL, and MPAL harboring 

 demonstrate gene signatures resulting in HOX and MEIS1 family gene proliferative deregulation (

). Blockage in myeloid differentiation and leukemia transformation are immediate biological consequences linked to these molecular defects. 

 de novo and therapy-induced pediatric and adult leukemias encode MLL1 subunits, such as MLL-N and MLL-C, which are capable of interacting with chromatin.

The menin-binding motif is highly preserved in all MLL fusion proteins and is considered a canonical cofactor for 

 gene transcription start sites/promoters.

Figure. Menin-Induced Epigenic Deregulation

Results of a preliminary safety and early efficacy analysis of revumenib demonstrated that 77.9% (n = 53/68) of 

) relapsed or refractory, previously heavily treated patients with AML developed any-grade treatment-related adverse effects (TRAEs).

 Any-grade QTc prolongation (52.9%), nausea (26.5%), and vomiting (16.2%) were frequently observed. With a median time to onset of 18 days, 16.2% of patients developed differentiation syndrome. The complication was linked to arthralgias, fever, leukocytosis, and pleural/pericardial effusion, and it was promptly resolved with the administration of steroids and hydroxyurea. The rate of complete remission (CR) or complete remission with a partial hematologic recovery (CR/CRh) was 30.0% (95%CI, 18.8%-43.2%) among evaluable patients with undetectable negative measurable residual disease (MRD), and the overall response rate (ORR) was 53.0%. 

Interestingly, transcriptomic modifications induced by revumenib were examined by RNA sequencing of hemopoietic cells reconfirming preestablished menin inhibition mechanisms of action associated with downregulation of 

 Preliminary data suggesting suppression of FLT3 expression indicated that revumenib’s benefit potentially expands beyond canonical 

 genomic defects. The recommended phase 2 dose (RP2D) was established as 276 mg every 12 hours (160 mg/m

 if < 40 kg) without a strong CYP3A4 inhibitor and 163 mg every 12 hours (95 mg/m

 if < 40 kg) for those on a strong CYP3A4 inhibitor. 

Phase 2 Trial, FDA Approval, and Novel Trial Design

The pivotal phase 2 AUGMENT-101 trial (NCT04065399) evaluated revumenib as monotherapy in patients with relapsed/refractory 

 AML or ALL. Ninety-seven pediatric and adult patients were included. The median age was 37.0 years (range, 1.3-75.0). At the time of enrollment, 43.6% of patients had received 3 or more anti-AML therapies. The most frequent TRAEs were nausea, differentiation syndrome, and QTc prolongation, which were observed in 27.7%, 26.6%, and 23.4 % of patients, respectively. Grade 3 or higher differentiation syndrome was observed in 16% of patients. In 57 patients included for efficacy analysis, the composite CR/CRh rate was 22.8%, surpassing the prespecified protocol null hypothesis of 10% (1-sided P=.0036); 70% of cases achieved MRD negativity.

 The median CR/CRh duration was 6.2 months (95% CI, 2.7-not estimable). Data demonstrated an unprecedented ORR of 63.2% for the single agent. Among 36 pediatric patients, CR/CRh rate was 23%, with 63% of patients achieving MRD negativity; the ORR was 46%. Fourteen (38.9%) patients who achieved a response had received allografting. 

These remarkable results positioned revumenib as a breakthrough for patients with relapsed/refractory acute leukemia harboring 

 translocation, a genomic defect historically associated with dismal outcomes. Additionally, AUGMENT-101’s clinical and biologic data prompted revumenib’s investigation in combination with intense chemotherapy and other targeted therapies (

Table 1. Revumenib Trials Exploring Synergistic Combinations and Novel Indications

Promising results for a “total oral therapy” regimen, including revumenib, were reported during the 66th American Society of Hematology Meeting and Exposition in December 2024.

 The phase 1/2 SAVE trial (NCT05360160) demonstrated an ORR of 82% (n=27/33). The most frequent TRAEs included QTc prolongation, febrile neutropenia, and nausea. Noticeably, early introduction of BCL-2 inhibitor and oral decitabine/cedazuridine substantially mitigated the risk of DS previously observed in the AUGMENT-101 trial (≥ grade 3 differentiation syndrome, 3% in SAVE). A subset of 

 leukemias present with hyperleukocytosis, suggesting that cytoreductive therapy in combination with a menin inhibitor is an important biologic strategy. 

AUGMENT-102 trial (NCT05326516), a phase 1 open-label study to investigate safety, tolerability, and preliminary antileukemic activity of revumenib in combination with chemotherapy in patients with relapsed/refractory leukemias harboring a 

 In this trial, fludarabine plus cytarabine are administered in combination with revumenib. The composite CR rate was 55.6% (95% CI, 21.2%-86.3%) among patients treated at dose level 1 (n = 9) and 50.0% (95% CI,26.0%-74.0%) among patients treated at dose level 2 (n = 18) in a predominantly pediatric population with a median age of 6 years (range, 0.8-78.0). No differentiation syndrome was reported. In addition to the potential for differentiation syndrome mitigation, synergy from drug combination and limited exposure to anthracycline with known cardiotoxic effect are the appealing AUGMENT-102 trial results. 

Further rationale supporting revumenib combination trials is based on the observation that terminal blast differentiation is immune transcriptomically associated with upregulation of CD11b and CD14 expression, and downregulation of 

 normally seen in fully differentiated effector myeloid cells.

deregulation is not only observed in NPM1-mutated AML and subset of 

 leukemias but is also an oncogenic addiction for several other leukemias. We may continue to uncover an expanding list of 

-like transcriptomic and/or methylome defects biologically relevant for menin inhibition.

Seven new and promising compounds that inhibit the 

transcriptional program are in clinical development. Among them, ziftomenib (KO-539; Kura Oncology) entered investigation in the phase 1/2 KOMET-001 trial (NCT04067336).

 The recommended RP2D of 600 mg was recently associated with a CR/CRh rate of 35%. At this dose level, differentiation syndrome was observed in 20% of patients. Remarkably, pharmacokinetic data did not demonstrate a major interaction between ziftomenib and CYP3A4 inhibitors. QTc prolongation was also not reported, differentiating it from other menin inhibitors in the class.

Another promising phase 1b trial (NCT05453903) is designed to address the safety and early efficacy of bleximenib (JNJ-75276617; Janssen) in combination with azacitidine (Vidaza) and venetoclax (Venclexta) in 

 To date, 60 and 34 patients were included in safety and early efficacy analyses, respectively. Interestingly, no evidence of differentiation syndrome was reported, albeit most adverse effects were restricted to nausea and vomiting. The ORR was 79%.

Additional invesigational agents include DSP-5336 (Sumito Pharma), DS-1594 (Daiichi Sankyo), BN104 (BioNova Pharmaceuticals), and icovamenib (BMF-219; Biomea Fusion).

The oral covalent menin inhibitor icovamenib is being evaluated in the phase 1 COVALENT-101 trial (NCT05153330). Preclinical data demonstrated the drug's ability to destabilize menin interaction with 

, modulate MYC expression, and regulate cell cycle pathways.

 Clinical efficacy was recently documented in adult post-allogeneic hematopoetic stem cell transplant patients with AML harboring 

 fusion. CR was documented on day 1 of chemotherapy treatment cycle 3 with 0% blasts.

The incorporation of menin inhibitors is central to improving the outcome of difficult-to-treat leukemias. However, there are barriers to overcome while targeting epigenetic codependencies. Importantly, that includes developing strategies that prevent clonal progression by acquisition of 

 and/or other epigenetic and nonepigenetic mutations. Monitoring 

 mutational allele frequency may prove advantageous, but in AML, single-cell clonal tracking could facilitate better drug combinations and personalized therapies.

Leukemia Program Research at Tampa General Hospital Cancer Institute

Tampa General Hospital Cancer Institute's leukemia program is primed for robust clinical and laboratory research. Adult patients with 

 AML have access to the phase 1 menin inhibitor clinical trial (NCT06313437) with revumenib in combination with cytarabine and daunorubicin (7+3) chemotherapy and midostaurin.

At our state-of-the-art biorepository, all samples from patients with AML, including those with the epigenetic mutations discussed, are collected and banked for ongoing and future collaborative research. Investigators have access to over 800 genomically diverse patients with AML in databases representing a multi-institutional effort to better dissect the acute leukemia genome. Sequential clonal inference, measurable residual disease, a large array of fusion proteins, and gene expression analysis have been incorporated into our databases.

Cuglievan B, Kantarjian H, Rubnitz JE, et al. Menin inhibitors in pediatric acute leukemia: A comprehensive review and recommendations to accelerate progress in collaboration with adult leukemia and the international community. 

. 2024;38(10):2073-2084. doi:10.1038/s41375-024-02368-7

Issa GC, Aldoss I, DiPersio J, et al. The menin inhibitor revumenib in KMT2A-rearranged or NPM1-mutant leukaemia. 

. 2023;615(7954):920-924. doi:10.1038/s41586-023-05812-3

Issa GC, Cuglievan B, DiNardo C, et al. Early results of the phase I/II study investigating the all-oral combination of the menin inhibitor revumenib (SNDX-5613) with decitabine/cedazuridine (ASTX727) and venetoclax in acute myeloid leukemia (SAVE). 

. 2023;142(suppl 1):58. doi:10.1182/blood-2023-182337

A phase I-II study Investigating the all oral combination of the menin inhibitor SNDX-5613 with decitabine/​cedazuridine (ASTX727) and venetoclax in acute myeloid leukemia (SAVE). ClinicalTrials.gov. Updated October 10, 2024. Accessed January 17, 2025. https://clinicaltrials.gov/study/NCT05360160

A study of revumenib in combination with chemotherapy in participants with R/​R acute leukemia. ClinicalTrials.gov. Updated August 13, 2024. Accessed January 17, 2025. https://clinicaltrials.gov/study/NCT05326516

Revumenib in combination with 7+3 + midostaurin in AML. ClinicalTrials.gov. Updated December 31, 2024. Accessed January 17, 2025. https://clinicaltrials.gov/study/NCT06313437

SNDX-5613 and gilteritinib for the treatment of relapsed or refractory FLT3-mutated acute myeloid leukemia and concurrent MLL-rearrangement or NPM1 mutation. ClinicalTrials.gov. Updated May 22, 2024. Accessed January 17, 2025. https://clinicaltrials.gov/study/NCT06222580

A phase II study of the menin inhibitor revumenib in leukemia associated with upregulation of HOX genes. ClinicalTrials.gov. Updated January 13, 2025. Accessed January 17, 2025. https://clinicaltrials.gov/study/NCT06229912

Issa GC, Cuglievan B, Daver N, et al. Phase I/II study of the all-oral combination of revumenib (SNDX-5613) with decitabine/cedazuridine (ASTX727) and venetoclax (SAVE) in R/R AML. 

. 2024;144(suppl 1):216. doi:10.1182/blood-2024-204375

Neerav S, Guest E, Tasian SK. Safety and activity of revumenib in combination with fludarabine/cytarabine (FLA) in patients with relapsed/refractory acute leukemias. Presented at: 2024 European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. Abstract P540.

Erba HP, Wang ES, Issa GC, et al. Activity, tolerability and resistance profile of the menin inhibitor ziftomenib in adults with relapsed or refractory NPM1-mutated AML. Presented at: 2023 European Hematology Association Congress; June 8-11, 2024; Frankfurt, Germany. Abstract LB2713.

Wei AH, Searle E, Aldoss I, et al. A phase 1b study of the menin-KMT2A inhibitor JNJ-75276617 in combination with venetoclax and azacitidine in relapsed/refractory acute myeloid leukemia with alterations in KMT2A or NPM1. Presented at: 2024 European Hematology Association Congress; June 13-16, 2024; Madrid, Spain. Abstract S133.

Somanath P, Lu D, Balakrishnan M, Butler T. Covalent menin inhibitor, BMF-219, impacts key gene signatures and molecular pathways in chronic lymphocytic leukemia patient-derived models. 

. 2023;83(suppl 7):473. doi:10.1158/1538-7445.AM2023-473

Carraway HE, Nakitandwe J, Cacovean A, et al. Complete remission of NUP98 fusion-positive acute myeloid leukemia with the covalent menin inhibitor BMF-219, icovamenib. 

. Published online December 5, 2024. doi:10.3324/haematol.2024.286537

Articles

The FDA's approval of revumenib, a menin inhibitor, marks a significant advancement in treating relapsed/refractory leukemias with KMT2A translocations. Revumenib targets epigenetic vulnerabilities, showing promise in clinical trials with notable response rates and manageable adverse effects. The AUGMENT-101 trial demonstrated its efficacy, leading to further exploration in combination therapies. Other menin inhibitors, like ziftomenib and bleximenib, are also under investigation, highlighting the potential of targeting HOX/MEIS1 pathways. Ongoing research aims to refine treatment strategies and overcome challenges in targeting epigenetic dependencies in leukemia.

Incorporation of menin inhibitors is central to improving the outcome of difficult-to-treat leukemias.

Targeting Menin: A New Frontier in Treating Refractory Leukemias

For a case of high-risk myelodysplastic syndrome [MDS], what are the newer medications that are on the table that might be very, very attractive? I would like to categorize this into 3 domains. The first domain is immune checkpoint inhibitors. Among them, we are paying significant attention to TIM-3 in combination with azacitidine. As you might remember, the combination has been associated with an overall response rate of 59% vs a single-agent HMA [hypomethylating agent] with a rate of about 42%. So the duration of response and the 1-year disease-free survival was 59% for the TIM3 inhibitor vs 32% for a single-agent HMA. So this is something that we should keep in mind for the case of 

[-mutated] MDS, even though the medication was paused recently by the FDA [United States Food and Drug Administration], we have a reactivation of enhanced 2 and 3. This will be for the medication magrolimab, which is a monoclonal antibody against CD47. CD47 is ubiquitously expressed in hematopoietic progenitors, and it's a molecule that might induce inhibition of prophagocytic activity by using the monoclonal antibody profile phagocytic activity increase stated, and it's preferentially observed among a subgroup of patients with 

-MDS. So we're paying significant attention to immune checkpoint inhibitors. And then I would like to move to the second domain which is the combination of azacitidine plus venetoclax, we have shown impressive responses, achieving almost 78% for high-risk MDS with excellent and durable remissions. The third domain would be the specific attention we should keep concerning those patients with high-risk MDS that are overexpressing RARA. As I mentioned before, almost 59% of these patients might upregulate RARA via super-enhancers. They've created an excellent biologic rationale for combination with HMA, and we will be paying attention to these 3 domains.

There will be a necessity—an urgent necessity, a biologic necessity—to understand biomarkers that respond to certain novel medications and biomarkers of durable response in high-risk MDS. So in regard to responses, I mentioned before that with the ability of immunophenotypic classification of MDS—whether or not we are going to be able to classify high-risk MDS in common myeloid progenitor-like disease or granulosa monocytic like-disease—we will be able to segregate a suitable patient that might be over expressing RARA. If that is the situation, then preferentially, we will derive or we will treat our patient with a combination of azacitidine and the RARAinhibitor. This is in the case that, potentially, we have a beneficial signal for the combination. So monocytic-like progenitors, AML [acute myeloid leukemia] have been associated with poorer responses to azacitidine and venetoclax, which I suspect will be the same situation for those patients with high-risk MDS. So phenotypic classification as a biomarker is emerging, and I'm expecting widespread use of this technology to better categorize the type of responses that we can have, to novel combinations of therapy. In regard to genomics, having P53 as an MDS-like disease should brand potentially, the possibility that immune checkpoint activation might be happening; therefore potentially using magrolimab in this setting might be beneficial.

Videos

Dr Gustavo Rivero comments on novel treatment combinations and potential new biomarkers in patients with MDS.

Future Perspectives in Higher-Risk MDS

The study SELECT-MDS-1 represents a significant advance in the way that we perceive the therapy of high-risk myelodysplastic syndrome [MDS]. We can lay out some ideas that might help us understand the rationale of combinational HMAs [hypomethylating agents] plus, the RARA [retinoic acid receptor alpha] inhibitor. I mentioned there is a subgroup of acute myeloid leukemia [AML] and patients with MDS who might overexpress RARA. It's conventionally believed that those patients that are overexpressing RARA might be less sensitive to venetoclax, which is a BCL-2 inhibitor. In the case of MDS it's expected [or] very likely in those patients who are exhibiting high expression of RARA to develop less sensitivity to hypomethylating agents. The combination will come from a set of recent developments, like trying to categorize MDS into 2 subgroups.

So the rationale for combinational HMA plus the RARA inhibitor will regain momentum and relevance if the classification of MDS can go beyond RIPSS-R [Revised International Prognostic Scoring System] only. I mentioned before that MDS could be categorized immunophenotypically as a CMP [common myeloid progenitor]-like disease and a GMP like-disease. CMP is a common myeloid progenitor MDS, and GMP is a granulocyte-monocytic progenitor-like disease. Granulocytic-monocytic progenitor disease is associated to likely have a high grade of RARA expression. This is a monocytic disease that has been historically associated with poor responses to HMAs like venetoclax, so I am predicting that it's likely that monocytic-like disease, MDS disease, might be responsive to this kind of normal combination.

The primary objective would be the overall response rate. And as I mentioned before, we will be able to determine the complete remission rate, the rate of partial remissions and hematologic improvement: erythroid, neutrophil, and platelet. I feel that with the development and the way that it has been strategized, the responses are appropriate.

How do I think azacitidine plus the RARA inhibitor might change the landscape of high-risk MDS? It will be extremely important to keep in mind that subgroup of patients with high-risk MDS, monocytic-like immunophenotypically, might exhibit a high grade of RARA overexpression. This condition might be associated with poor outcomes through a standard therapy of HMA—azacitidine or decitabine. So adding a RARA inhibitor that can stabilize the levels of RARA and induce further differentiation might improve significantly and very likely to respond beyond single-agent azacitidine and decitabine. Side effect-wise, remember for single-agent azacitidine cytopenia has been remarkable from cycle 1 to cycle 4. However, after cycle 4 the degree of cytopenia-transfusion dependency is minimized entirely as MDS-like cells are deleted. For the RARA inhibitor, the number of side effects has not been meaningful. I think grade 1/2 anemia has been described at initial therapy; however, these are not entirely magnified, synergized by the use of azacitidine or decitabine.

So for the side effects of the RARAinhibitor, I briefly mentioned that grade1 or 2 anemia has been described in almost 20% of the patients; however, in combination with azacitidine, it hasn't surpassed that level. A second adverse event is QT prolongation, grade 1 or 2, which has been mostly observed as a single agent. However, in combination with azacitidine, it also hasn’t passed that level.

A whole proportion of patients who are receiving hypomethylating agents in combination with their RARA antagonist experienced differentiation syndrome, which is characterized by a rapid increase in cytokines and is associated with hypoxemia, shortness of breath, swelling, and weight gain. There was some of this, and it is an additional adverse event that we should keep in mind.

Gustavo Rivero, MD, comments on the ongoing SELECT-MDS-1 trial and as well as reviewing the adverse events of the potential combination of tamibarotene with azacitidine in patients with higher-risk MDS.

SELECT-MDS-1: Review of Study Design and Objectives

: Historically, the 3 main high-risk myelodysplastic syndrome [MDS] have been concentrated on the use of hypomethylating agents. The 2 FDA [United States Food and Drug Administration]-approved agents are azacitidine and decitabine. These 2 agents’ composite overall response is about 45%, with almost 15% of the cases representing complete remission. The rest is an erythroid response of platelets and myeloid responses. So the 2 agents are equal in efficacy, but as I mentioned before, a substantial group of patients might exhibit primary refractoriness, and almost every single patient responding to the medication will develop secondary refractoriness.

The recent designation of tamibarotene as an orphan medication by the FDA represents an advance in the potential management of high-risk MDS. I just want to comment regarding the mechanism of action. I mentioned before that most of the data is being extrapolated from acute myelogenous leukemia. Specifically, a recent publication in 

 has revealed that pediatric acute myeloid leukemia [AML] may express in the same way adult AML expressesRARA [retinoic acid receptor, alpha] 

 super-enhancer. I explained that a super-enhancer is a new gene for which leukemia might develop an addiction, and these genes are no more than transcriptional deregulation in acute myelogenous leukemia. So, tamibarotene is a RARA agonist that creates a balance between the ligand, which is retinoic acid, and RARA overexpression by itself. By restoring RARA, acute differentiation might occur in cells that are specifically leukemic, but in the case of MDS, it is expected to leave about the same clinical benefit.

Dr Gustavo Rivero reviews the treatment options for patients with newly diagnosed higher-risk MDS and discusses tamibarotene’s recent orphan drug designation. 

A Potential Role for Tamibarotene in the Treatment of Higher-Risk MDS

 [gene expression] mean in the context of myelodysplastic syndrome [MDS]? I want to emphasize that most of the work has initially been done on acute myelogenous leukemia [AML], and this is an extrapolation of information about such a horrible disease. 

 is normally overexpressed in hematologic malignancy, via activation of super-enhancers. I want to explain what a super-enhancer is. It’s a new form of gene expression in our genome that isn’t expressed in normal conditions. Super-enhancers for 

 have been observed in almost 59% of acute myelogenous leukemia, which I think in the setting of high-risk MDS may be extremely relevant because it might be about the same proportion as in AML. So this overexpression of 

 is counter-regulated by retinoic acid ligands, and there is a significant imbalance between the ligand and the expression of 

We are seeing with significant enthusiasm the development of tamibarotene, which is a RARA agonist that restores the imbalance between the ligand and 

Dr Gustavo Rivero talks about the significance of the RARA gene in patients with higher-risk MDS. 

RARA Gene Expression in Higher-Risk MDS

: I am Gustavo Rivero. I am an associate professor in hematology-oncology at Baylor College of Medicine [Houston, Texas]. I concentrate my efforts on treating acute myelogenous leukemia and myelodysplastic syndrome [MDS].

I want to emphasize that myelodysplastic syndrome is a very unique entity. It's mainly classified as an apoptotic-like disease and being more resistant to apoptosis. It is a spectrum of disorders that we normally can distinguish by classifying the entity via the Revised International Prognostic Scoring System. There are some items that we should keep in mind for the risk stratification, which include the depth of anemia, thrombocytopenia, neutropenia, the number of blasts, and specifically the cytogenetic abnormalities that the patient might have at disease initiation. So the risk stratification allows a subcategorization for these entities into a low-risk biology and a high-risk biology. Points are assigned in an increasing mode; the higher the score, the more likely the patient will have high-risk disease vs with a low score, the patient will be categorized as having a low-risk disease. This is normally what we do in clinical practice every day.

Biomarker testing is becoming extremely relevant for acute myelogenous leukemia and myelodysplastic syndrome. There is an increasing necessity for detecting what type of drugs might be implemented in subcategories of patients with MDS. Specifically, we have retained a very agnostic therapy, which is an intravenous hypomethylating agent. Hypomethylating agents are azacitidine and decitabine, which are medications that have been associated with an overall response rate of 45%. However, there is a group of patients who won’t respond to the intervention, and these subgroups of patients are categorized as primary refractory. Almost every patient responding to the medication will develop secondary failure.

So biomarker testing is especially important because it will select the patients who might respond to normal interventions. Among them, we have recent evidence that subcategorization for MDS is grouped into monocytic-like and myeloid-like. These MDS groups might reveal a path for incorporation of novel therapies like RARA inhibition, and even a subgroup of patients in the high-risk setting who might respond better to BCL2 inhibition.

An overview of myelodysplastic syndrome (MDS) and the role of biomarker testing in patients with the disorder.

Overview of Myelodysplastic Syndrome and the Importance of Biomarker Testing

Gustavo Rivero, MD, associate professor, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, discusses evolving therapies for patients with acute myeloid leukemia (AML) with monocytic differentiation.

The current standard of care for patients with AML who are ineligible for intensive chemotherapy is the combination of a hypomethylating agent (HMA) and venetoclax (Venclexta), Rivero says. However, patients with monocytic differentiation often display inferior responses to this regimen, Rivero explains.

Recent evidence suggests that AML with monocytic differentiation can have lower BCL-2 expression and higher MCL-1 expression, potentially explaining their resistance to HMAs and venetoclax and serving as prognostic markers.

Sponsored in part by Servier Pharmaceuticals. Content independently developed by OncLive.

Gustavo Rivero, MD, discusses evolving therapies for patients with acute myeloid leukemia with monocytic differentiation.

Gustavo Rivero, MD