Stuart L. Goldberg, MD
The treatment landscape of acute myeloid leukemia (AML) has undergone a significant transformation in the past year with the introduction of many novel agents, says Stuart L. Goldberg, MD.
In 2017 alone, gemtuzumab ozogamicin (Mylotarg), CPX-351 (Vyxeos), midostaurin (Rydapt), and enasidenib (Idhifa) were all approved by the FDA for the treatment of patients with AML. Additionally, the FDA granted a priority review to ivosidenib (AG-120) for the treatment of patients with relapsed/refractory IDH1
Additionally, venetoclax (Venclexta) was granted an FDA breakthrough therapy designation in July 2017 for use in combination with low-dose cytarabine in treatment-naïve elderly patients with AML who are ineligible for intensive chemotherapy.
Although there has been much success in this field, Goldberg said that the focus needs to be put on elderly patients, as well as patients with myelodysplastic syndrome (MDS), a precursor to AML. In contrast to AML, MDS has experienced little success in the last decade, Goldberg said.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Hematologic Malignancies, Stuart, a hematologist in the Division of Leukemia at John Theurer Cancer Center, and chief scientific officer of Cota, discussed the management of patients with AML as well as those with MDS.
OncLive®: Please provide an overview of your presentation.
: Prior to 2017, the management and evaluation of patients with AML was relatively simple. We would decide whether the patient was fit or unfit for therapy, and if they were fit, we would offer them standard induction chemotherapy. We have done that for 40 years. The management of AML has changed dramatically in the past year with the approval of several new agents. AML is no longer a simple disease; it is complex, and the evaluation needs to be done properly so that we can select the right patient for the right therapy.
Can you speak to how these new approvals have impacted the field?
This has truly been a banner year with the FDA approval of 4 new agents. Also, we have seen the use of other approved agents in AML that are showing efficacy in the elderly population. The field has become fairly complex; you need to do a very good workup because each of our agents are geared toward a specific subtype.
AML is an extremely complex disease at a genetic and chromosomal level. Up until now, we have used chromosomes mostly to determine whether a patient should get a bone marrow transplant or if they should get consolidation chemotherapy for risk stratification. However, with the introduction of the molecular tests, we can now give targeted therapies.
When I see a brand-new patient, I have to look at their history. Do they have a history of myelodysplastic changes or secondary AML? In that case, I might be using CPX-351. I have to look and see if they have a genetic alteration of FLT3
, because then I might be using a FLT3 inhibitor upfront such as midostaurin, or we may want to think about some of the experimental agents in the second-line setting. If they have an IDH
mutation, we now have a drug for IDH2
, and we will probably soon have one for IDH1
. If the patient has a core-binding factor, a common chromosome abnormality, there may be a role for gemtuzumab ozogamicin. Each of these new drugs have a specific area where they seem to be shining.
Could chimeric antigen receptor (CAR) T-cell therapy have potential in this field?
The whole field of oncology is changing with the development of immunotherapies, which to date have not been very successful in AML or MDS. We do see the development of CAR T cells as a potential future [option]. It has already shown promise in lymphomas and myeloma, and we have targets on myeloid cells such as CD33 that may be a potential target for CAR T cells in AML. The work is fairly early, but there may be a future for CAR T cells in relapsed patients, similar to what we have seen in acute lymphocytic leukemia in patients who have relapsed after bone marrow transplant.
Venetoclax in combination with low-dose cytarabine has shown promise. Could you share some insight on that?
Most of the focus this past year has been on the development of new agents which have been used for the younger, healthier, fit patients. However, we desperately need agents to treat the older, unfit patients. In the past few years, we have used hypomethylating agents such as 5-azacitidine or decitabine, and sometimes low-dose cytarabine.