Dr Daver on the Evolution of Survivorship and Treatment Outcomes in AML

Naval G. Daver, MD, professor, director, Leukemia Research Alliance Program, Department of Leukemia, Division of Cancer Medicine, The University of MD Anderson Cancer Center, discusses the evolution of survivorship in patients with acute myeloid leukemia (AML).

The outlook for AML survivorship has significantly improved over time, Daver begins. A decade ago, options were limited for patients who progressed on standard frontline therapy, such as intensive chemotherapy likeanthracyclines and cytarabine. At that time, no targeted therapies existed; FLT3 inhibitors, IDH inhibitors, and MDM2 inhibitors had not been developed yet, nor had venetoclax (Venclexta) either alone or in combination with hypomethylating agents (HMAs), he reports. Consequently, AML prognosis was dire, with patients having response rates of only 15% to 18% using HMAs alone and even lower rates with low-dose cytarabine, Daver explains. Therefore, approximately 90% of patients had palliative outcomes, according to Daver.

Today, the management of relapsed AML has dramatically changed, Daver continues. The ability to identify molecular targetable mutations, such as 

, as well as various fusions and translocations, has become pivotal, he reports. These mutations are found in approximately 55% to 60% of patients, allowing for the use of targeted therapies that yield response rates between 40% to 80%, which is highly encouraging, he emphasizes. Additionally, targeted approaches open the possibility of transitioning patients to allogeneic stem cell transplants, Daver notes.

For those without targetable mutations, venetoclax-based therapies, including combinations with HMAs or intensive chemotherapy, have become viable options, producing response rates of 40% to 70%, he expands. This shift represents a significant change from 10 to 15 years ago, offering new hope for potential cures, according to Daver.

Although cure rates for relapsed and refractory AML still require improvement, ongoing research into immunotherapies—similar to those used in acute lymphoblastic leukemia, multiple myeloma, and large B-cell lymphoma—holds promise, Daver states. Despite challenges, there is growing optimism that survival can be extended and quality of life can be improved for relapsed AML, he concludes.

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Naval G. Daver, MD, discusses the evolution of survivorship in patients with acute myeloid leukemia.

Naval Daver, MD, associate professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the unmet needs for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN).

Although BPDCN is a relatively rare disease, it has emerged as a unique entity over within the past decade, Daver notes. Researchers have identified certain markers that can be used to identify this disease, including CD123, TCF4, TCL1, CD4, and CD56. Identifying these flow-based markers can be used to identify patients with BPDCN and differentiate their disease from other malignancies, such as acute myeloid leukemia (AML), Daver says. Additionally, certain mutations have a higher prevalence in patients with BPDCN, including 

When the FDA approved tagraxofusp-erzs (SL-401; Elzonris) for the treatment of adult and pediatric patients aged at least 2 years with BPDCN in December 2018, the first-in-class CD123-targeted therapy became the first agent approved for the treatment of the disease. Since treatment for BPDCN varies from other hematologic malignancies such as AML, it is important to identify this disease group and differentiate it from others because this will have a direct therapeutic impact, Daver emphasizes.

Although advancements have been made in BPDCN in the past 10 years, including the FDA approval of tagraxofusp, a big need remains for increased awareness and education about this unique and rare condition, Daver notes.

Developing combination strategies, which have made inroads in other malignancies, could potentially provide additional beneficial treatment options for patients with BPDCN.

Referring patients with BPDCN to clinical trials will be critical to investigate novel therapies and get new drug approvals, Daver says. Given the rarity of BPDCN, finding clinical trials from them could provide additional treatment avenues and help develop new options, Daver concludes.

Naval Daver, MD, discusses the unmet needs for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm.

Dr. Daver on Unmet Needs in the Treatment of BPDCN


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We are reporting from the 2021 ASH Annual Meeting!

We have been highlighting some of the top news presented each day during the meeting—and soon we’ll speak with Dr. Srdan Verstovsek on the pivotal data in myeloproliferative neoplasms, and Dr. Naval Daver on some intriguing findings in acute myeloid leukemia.

Welcome to OncLive News Network! I’m Gina Mauro.

Primary results from the phase 3 ZUMA-7 trial showed that axicabtagene ciloleucel led to a 60% improvement in event-free survival compared with standard-of-care chemotherapy as second-line treatment for patients with relapsed/refractory large B-cell lymphoma.

In a quality of life analysis of the ZUMA-7 trial, axicabtagene ciloleucel resulted in clinically meaningful improvement in quality of life at day 100 compared with standard of care as a second-line treatment of patients with relapsed/refractory large B-cell lymphoma.

The addition of ublituximab and umbralisib to ibrutinib produced deep remissions with favorable tolerability in patients with chronic lymphocytic leukemia who previously received ibrutinib and still had detectable minimal residual disease in a phase 2 trial. Results indicated that 77% of those who went on to receive the triplet combination achieved undetectable minimal residual disease.

Asciminib demonstrated a consistent improvement in major molecular response rate and depth of response vs bosutinib in patients with chronic-phase chronic myeloid leukemia without any new or worsening adverse effects, according to updated findings from the phase 3 ASCEMBL trial.

Results from a meta-analysis of the phase 1/2 CARTITUDE-1 trial showed that ciltacabtagene autoleucel demonstrated a significant advantage over physician’s choice of treatment with regard to overall survival, progression-free survival, time to next treatment, and overall response rate, underscoring its potential for use in patients with triple-class relapsed/refractory multiple myeloma.

Please be sure to check out more of our coverage from the 2021 ASH Annual Meeting at OncLive.com.

That’s all for today. Thank you for watching OncLive News Network: On Location. Signing off from the 2021 ASH Annual Meeting, I’m Gina Mauro.

OncLive® speaks with Dr. Srdan Verstovsek on the pivotal data in myeloproliferative neoplasms, and Dr. Naval Daver on some intriguing findings in acute myeloid leukemia.

Updates in AML and MPNs From ASH 2021: From Drs Srdan Verstovsek and Naval Daver 

Naval G. Daver, MD, associate professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, discusses the mechanism of action of the investigational CD47-directed antibody magrolimab in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

CD47 is an immune checkpoint that lies on the surface of macrophages, says Daver. In AML, macrophage suppression and exhaustion are caused by cancer cells that use a link between CD47 and signal regulatory protein alpha.

By blocking CD47 with an agent such as magrolimab, macrophages are not exhausted, explains Daver. Instead cancer cells omit an “eat-me” signal allowing the macrophages to attack.

Magrolimab may have utility across many tumor types. However, preclinical data in immunodeficient mouse models demonstrated prolonged survival and rapid responses with magrolimab in combination with the hypomethylating agent azacitidine, says Daver.

As such, ongoing studies are evaluating the combination in patients with AML/MDS, as well as in patients with lymphoma and solid tumors, concludes Daver.

Naval G. Daver, MD, discusses the mechanism of action of the investigational CD47-directed antibody magrolimab in acute myeloid leukemia and myelodysplastic syndrome.



Dr. Daver on the Mechanism of Action of Magrolimab in AML/MDS

Naval Daver, MD, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses single-agent immunotherapy in acute myeloid leukemia (AML).

Although single agent PD-1 inhibition has not shown activity in AML, single agent CTLA-4 inhibition may have a role, says Daver. For example, promising data has been shown with ipilimumab (Yervoy) as a single agent in patients with AML.

Not all checkpoint inhibitors are equal, says Daver, and combinations will likely be the future of immunotherapy in AML.

Naval Daver, MD, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses single-agent immunotherapy in acute myeloid leukemia.
 

Dr. Daver Discusses Single-Agent Immunotherapy in AML

Naval Daver, MD, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the approval of a chimeric antigen receptor (CAR) T-cell therapy in pediatric acute lymphoblastic leukemia (ALL).

Tisagenlecleucel (Kymriah) is for the treatment of patients up to 25 years of age with B-cell precursor ALL that is refractory or in second or later relapse.

Daver says that he believes the success seen in this setting with CAR T-cell therapy will spread to adult and older populations, as well.

Naval Daver, MD, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses the approval of a chimeric antigen receptor (CAR) T-cell therapy in pediatric acute lymphoblastic leukemia.

Dr. Daver on CAR T-Cell Therapy Approval in Pediatric ALL

Naval Daver, MD, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses research evaluating different immune checkpoint pathways in patients with acute myeloid leukemia (AML).

Since nivolumab (Opdivo) and other immune checkpoint drugs have shown exciting results in a number of other solid tumors, researchers are now turning their attention toward these different immune checkpoint pathways in the treatment of patients with AML.

Daver provides an overview of a study in which the investigators collected bone marrow tissue samples and blood from patients with AML. After analyzing those samples, they found that the 2 checkpoint pathways that seemed to be overexpressed in the bone marrow were PD-1 and OX40.

Based on those findings, he says, multiple clinical trials began in different patient populations—including those with AML, myelodysplastic syndrome, and chronic lymphocytic leukemia&mdash;to see if the researchers could target this overexpression of PD-1 in the bone marrow, increase T cell activity, and improve responses&mdash;or durability of responses&mdash;in these patients. Moreover, these results ultimately provide a strong rationale for further research into immune checkpoint pathways in AML and other hematologic malignancies.

Naval Daver, MD, assistant professor, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, discusses research evaluating different immune checkpoint pathways in patients with acute myeloid leukemia.

Naval Daver, MD

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