William B. Donnellan, MD, investigator, Hematologic Malignancies, Sarah Cannon Research Institute, Tennessee Oncology, discusses ongoing trials in hematologic malignancies.

In acute myeloid leukemia (AML), venetoclax (Venclexta) showed a very high response rate when used in combination with a hypomethylating agent in newly-diagnosed patients. There is now a large phase III study launching, which will compare azacitidine either in combination with venetoclax or placebo. The outcome of this trial could potentially change how older patients with AML are treated.

There are several trials ongoing in myelofibrosis, such as the PAC203 study. This study is evaluating pacritinib, a JAK/FLT inhibitor, which has been shown to be effective in patients with myelofibrosis who are resistant or refractory to ruxolitinib (Jakafi). There are some concerns about toxicity, specifically cardiac and hematologic events.

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William B. Donnellan, MD, investigator, Hematologic Malignancies, Sarah Cannon Research Institute, Tennessee Oncology, discusses ongoing trials in hematologic malignancies.
 

Dr. Donnellan Discusses Trials in Hematologic Malignancies

William B. Donnellan, MD, investigator, Hematologic Malignancies, Sarah Cannon Research Institute, Tennessee Oncology, discusses combinations under investigation in acute leukemia.

In 2017, there were 7 new drug approvals in acute leukemia. Donnellan says that the next big question is whether this new crop of agents will demonstrate added benefit when combined. Specifically, Donnellan says that investigators need to determine whether there is an added benefit of combining CPX-351 with a FLT3 inhibitor, such as midostaurin (Rydapt), or with some of the second-generation FLT3 inhibitors. Or, whether combining enasidenib, the IDH2 inhibitor, with other small molecules in patients with secondary acute myeloid leukemia (AML) who also have a

Combinations are something to look forward to, says Donnellan. One of the big stories out of the 2017 ASH Annual Meeting was venetoclax (Venclexta), which showed very high response rates when used in combination with a hypomethylating agent in patients with newly diagnosed AML.

A phase III study is set to launch comparing azacitidine either in combination with venetoclax or placebo. That trial could potentially change the treatment paradigm for elderly patients who are not fit for induction, Donnellan says.

William B. Donnellan, MD, investigator, Hematologic Malignancies, Sarah Cannon Research Institute, Tennessee Oncology, discusses combinations under investigation in acute leukemia.
 

Dr. Donnellan on Combinations Under Investigation in Acute Leukemia

William B. Donnellan, MD, investigator, Hematologic Malignancies, Sarah Cannon Research Institute, Tennessee Oncology, reflects on some of the most pivotal FDA approvals in acute leukemia in the past year.

Donnellan says that 2017 was a blockbuster year for drug approvals in acute leukemia. August 2017 brought about a few FDA approvals for the treatment of patients with acute leukemia, such as acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Enasidenib (Idhifa) as a treatment for patients with relapsed or refractory 

-mutated AML, based on a phase I/II study that showed a complete remission rate of 19.3 in this patient population. Also in AML, CPX-351 (Vyxeos), a fixed-combination of daunorubicin and cytarabine, for adult patients with newly diagnosed therapy-related AML or AML with myelodysplasia-related changes was approved by the FDA.

In ALL, inotuzumab ozogamicin (Besponsa) was approved for the treatment of adults with relapsed or refractory B-cell precursor acute ALL, based on findings from the phase III INO-VATE trial. And rounding out August, tisagenlecleucel (Kymriah) was approved for the treatment of patients up to 25 years of age with B-cell precursor ALL.

William B. Donnellan, MD, investigator, Hematologic Malignancies, Sarah Cannon Research Institute, Tennessee Oncology, reflects on some of the most pivotal FDA approvals in acute leukemia in the past year.
 

Dr. Donnellan Reflects on FDA Approvals in Acute Leukemia

William B. Donnellan, MD, investigator, Hematologic Malignancies, Sarah Cannon Research Institute, Tennessee Oncology, discusses combinations in light of newly FDA-approved agents in acute myeloid leukemia (AML).

In 2017, there were many FDA approvals in the world of AML. Now, physicians are determining optimal combinations for their patients. In patients with secondary AML who also have a FLT3 mutation, the focus of research will be in determining whether there is an added benefit in combining CPX-351 (Vyxeos) with a FLT3 inhibitor like midostaurin (Rydapt), or some of the second-generation FLT3 inhibitors with the IDH2 inhibitor, enasidenib (Idhifa).

Combinations with developing drugs are also being investigated. The big story at the 2017 ASH Annual Meeting was venetoclax. In newly diagnosed AML, the agent showed high response rates when used in combination with a hypomethylating agent. Rates of response are almost 3 times what would be expected with a hypomethylating agent alone.

There's also a big phase III study that’s launching that will compare azacitidine either in combination with venetoclax or placebo. That could potentially change the treatment paradigm for elderly patients who are not fit for induction.

Dr. Donnellan on Developing Combinations in AML

William B. Donnellan, MD, investigator, Hematologic Malignancies, principal investigator, Sarah Cannon Research Institute, discusses preliminary results of the ENESTop study, which explored treatment-free remission (TFR) in patients with chronic myeloid leukemia (CML) in chronic phase who were treated with second-line nilotinib (Tasigna).

While nilotinib demonstrates promising activity in patients, it is associated with high costs as well as toxicities, Donnellan explains. In this study, patients were treated with nilotinib for 1 year. If they remained in complete remission, treatment with nilotinib was discontinued and patients were closely observed. 

Sixty percent of patients were found to remain in a complete remission at about 48 weeks after discontinuing treatment. Additionally, 98% patients who came out of remission, and then continued with treatment with nilotinib, were able to re-enter remission.

William B. Donnellan, MD, investigator, Hematologic Malignancies, principal investigator, Sarah Cannon Research Institute, discusses preliminary results of the ENESTop study, which looked at treatment-free remission (TFR) in patients with chronic myeloid leukemia in chronic phase who were treated with second-line nilotinib (Tasigna).

William B. Donnellan, MD

Articles

Dr. Donnellan Discusses Trials in Hematologic Malignancies

Dr. Donnellan on Combinations Under Investigation in Acute Leukemia

Dr. Donnellan Reflects on FDA Approvals in Acute Leukemia

Dr. Donnellan on Developing Combinations in AML

Dr. Donnellan on TFR in Patients With CML Treated With Nilotinib