ASH 2015 Preview: Novel Agents, Combinations Abound Across Hematologic Malignancies

Gina Columbus @ginacolumbusonc
Published: Thursday, Dec 03, 2015

In less than 5 years, the treatment landscape for patients with hematologic malignancies has undergone a dramatic transformation, with continued advancements and pivotal data being presented at the 2015 American Society of Hematology (ASH) Annual Meeting from December 5 to 8.

 

“We have witnessed a tremendous growth of therapeutic options in a number of hematologic malignancies,” said Gary Schiller, MD, who specializes in hematology and oncology in the Department of Medicine, Hematology and Oncology at the Ronald Reagan UCLA Medical Center. “There have been so many changes in this last decade that I think hold promise for the future for most hematologic malignancies. They will not only be much easier to control and induce long-term survival, but there will be far fewer off-target therapies.”

 

The recent explosion in novel therapies for patients with multiple myeloma and chronic lymphocytic leukemia (CLL) is evident in the list of upcoming oral presentations at the upcoming ASH meeting. In an interview with OncLive, Schiller, who is an appointed ASH spokesperson, highlighted some of the top findings being presented at this year’s meeting.

 

In acute myeloid leukemia (AML), Schiller highlighted data that will be presented for the multikinase inhibitor midostaurin (PKC412). This novel agent was shown to prolong survival compared with placebo, when used in combination with daunorubicin/cytarabine induction, high-dose cytarabine consolidation, and as maintenance therapy in newly diagnosed patients with FLT3-mutated AML.

 

In the large phase III international study, 717 patients with untreated AML received midostaurin or placebo. According to an abstract released prior to the meeting, patients who received midostaurin experienced a 23% improvement in overall survival (OS) compared with the placebo arm (HR, 0.77; 0.63-0.95; P = .007).

 

“That is a positive trial with a survival advantage in the treatment group. That is a potential game-changer. Part of that is because we have had so little progress,” Schiller said. “Here, you have a huge study upfront that shows survival advantages. Therefore, I think it will force the FDA to consider approving midostaurin, and that will have a big impact both within that indication for upfront management and maybe for FLT3-mutated patients in other settings.”

 

Venetoclax (ABT-199/GDC-0199) is another novel agent with promising upcoming data at the ASH meeting that could also be instrumental in FDA approval, according to Schiller. This agent demonstrated deep remissions in a phase II study for ultra-high risk patients with relapsed/refractory CLL with 17p deletion.

 

In the abstract for the study, the objective response rate (ORR) with venetoclax monotherapy was 79.4% by independent review. Complete responses (CR) or CRs with incomplete hematologic recovery were experienced by 7.5% of patients.

 

“Venetoclax has shown a lot of single agent activity in CLL; it is a very interesting drug. CLL is a very common disease, for which there have not been a lot of therapeutic advancements in the last year,” Schiller said. “Here, we have another drug that has a lot of single-agent activity. It stands to reason that more combinations might be studied in the future.”

 

Outside of investigational agents, a number of reports will focus on already approved treatments under exploration for new indications. These studies are looking at a host of treatments, including rituximab (Rituxan), idelalisib (Zydelig), ibrutinib (Imbruvica), ixazomib (Ninlaro), elotuzumab (Empliciti), and daratumumab (Darzalex).

 

Schiller noted that data would be presented from the phase II RESONATE-2 trial, which examined the efficacy of ibrutinib versus chlorambucil in elderly patients with treatment-naïve CLL or small lymphocytic leukemia. The drug is already approved in relapsed/refractory disease as well as in 17p deletion CLL.

 

Treatment with single-agent ibrutinib was shown to be superior to chlorambucil across all measurements of efficacy. Overall, ibrutinib reduced the risk of death by 84% compared with chlorambucil, according to the abstract. Updated data from this study will be presented during a late breaking abstract session.

 

“It is the newly diagnosed patients with CLL who need treatment. I think the abstract that will be presented could be a potential game changer that could influence our prescribing behavior right away,” Schiller said.

 

Regarding the future treatment paradigm of CLL, use of bendamustine and rituximab (BR) could evolve, as shown in results of a phase III study which showed that idelalisib plus BR was superior to BR alone. On November 16, 2015, Gilead Sciences, the manufacturer of idelalisib announced that it had stopped this trial early following a positive interim analysis. These data add to the prior HELIOS trial, which explored ibrutinib plus BR in CLL.

 


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