Michael R. Grunwald, MD
While tremendous strides have been made in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), challenges remain in both paradigms, including optimal sequencing and managing toxicity profiles, explained Michael R. Grunwald, MD.
“Things are getting better both for patients with AML and those with ALL,” Grunwald said. “We're seeing progress from decade to decade, and a lot of it has been advances in supportive care and decreased toxicity of transplant. Now, we have some new agents in the mix, and I'm very hopeful that we're going to be able to offer patients therapies that are both gentler and more efficacious in the near future.”
Among the therapies available for patients with ALL, inotuzumab ozogamicin (Besponsa) is associated with hepatotoxicity, especially in patients with liver disease. Moreover, blinatumomab (Blincyto) may be linked with neurotoxicity and cytokine release syndrome.
For AML, several new therapies have been added to the treatment armamentarium that have been shown to improve survival in both the frontline and relapsed/refractory setting. As the sequence of these agents is further refined, physicians are hopeful that they will be able to deliver more effective, less toxic treatments than stem cell transplantation, said Grunwald.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Hematologic Malignancies, Grunwald, a physician at Levine Cancer Institute, discussed new and emerging agents in AML and ALL, as well as sequencing and toxicity challenges with these treatments.
OncLive: Please provide an overview of your presentation.
: I presented on new therapies in acute leukemia, specifically AML and ALL. For many decades, we didn't have new therapies, especially for AML. Over the past few years, especially this past year, we've gotten some exciting new drug approvals in both AML and ALL.
First, I addressed AML and the areas of need in this patient population. There are a lot of challenges in various groups. One challenge is the relapsed/refractory population; these are the patients who either don't respond to therapy or who were in remission and later come out of remission. We have a group of patients whom we consider elderly. These are generally patients over 60 and carry a poor prognosis.
Then, we have challenges related to certain groups of patients with specific mutations or abnormalities, including FLT3
mutations, which carries a poor prognosis. There are IDH1/2
mutations, which have been recently discovered to be targetable, and p53
mutations, which carry poor prognosis in AML and in other diseases.
For AML, therapies that are new to our armamentarium include the FLT3 inhibitor midostaurin (Rydapt). Midostaurin has been shown to improve overall survival in combination with induction therapy if patients have a FLT3
mutation. We also discussed frontline therapies for secondary AML, including therapy-related and myelodysplastic syndrome-derived AML. CPX-351 (Vyxeos) is the liposomal 7+3 [daunorubicin and cytarabine] that has been shown to improve survival in secondary AML in patients aged 60 to 75.
Gemtuzumab ozogamicin (Mylotarg) is a therapy that has recently been reapproved for AML, both as upfront therapy and in the relapsed/refractory setting. For IDH2
-mutated patients, I discussed enasidenib (Idhifa), which is a targeted therapy that's approved for patients with relapsed/refractory AML harboring the IDH2
I also discussed some therapies that are currently in development. Ivosidenib is an exciting therapy for patients with IDH1
-mutated AML. We have venetoclax (Venclexta), which is a therapy currently approved for [patients with] chronic lymphocytic leukemia. It's used off-label to treat patients with AML and might be an option in the future for patients with AML as further trials investigate this agent both alone and in combination with hypomethylating agents.
I also discussed decitabine, which is an approved therapy used commonly for AML. It has shown efficacy specifically in the patient population with p53
In ALL, I spoke about the challenges in that disease, which consist of older, relapsed/refractory patients and those with a Philadelphia chromosome (Ph). I also discussed some therapies that have been approved in recent years. Ponatinib (Iclusig) is efficacious in the Ph-positive population. Blinatumomab is a CD19/CD3 bispecific antibody approved in the relapsed/refractory setting and the minimal residual disease setting. Inotuzumab ozogamicin is also an agent approved for relapsed/refractory ALL that targets CD22.