Emerging Treatments and Trends in Hematologic Malignancies: A Q&A With Anas Younes, MD
Published Online: Wednesday, April 30, 2014
Anas Younes, MD
The FDA is currently reviewing New Drug Applications for idelalisib in chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin lymphoma (iNHL). What has the data shown in support of the drug’s efficacy?The PI3K delta specific inhibitor idelalisib has demonstrated significant activity in both relapsed CLL and relapsed follicular lymphoma. The CLL results came from randomized trials, so it was easy to compare treatments and get the data. The relapsed follicular lymphoma data was in patients who were refractory to both alkylating agents and rituximab, which is an area of unmet medical need. About 57% of these patients responded to single-agent oral therapy, which is remarkable.
Ibrutinib is now approved for mantle cell lymphoma and CLL. What are your thoughts on the potential for sequencing ibrutinib and idelalisib?Right now, there is no guidance as to which one you should start with. It is going to be based on what is available, what sort of indication, what is the fine print on the indication, what are the future guidelines from the NCCN, and so forth. You will likely have a group of patients who could be eligible for both, and it is difficult to pick one over the other.
There are some groups, however, that have clear contraindications. For example, ibrutinib should not be given to patients on an anticoagulant, such as Coumadin. That set should receive idelalisib.
This is not the first time where we have multiple options, and, in the end, the treating oncologist and the patient discuss the pros and cons of each one and decide to go with one over the other. It is good to have more than one option.
Other agents being developed in this space include IPI-145 and ABT-199. What are your thoughts on these therapies?IPI-145 is a gamma and delta pathway kinase inhibitor, so it has a wider range of activity than idelalisib. It seems to have good activity across different lymphoma malignancies, including indolent lymphoma, MCL, CLL, and T-cell lymphoma. It will be interesting to see where this will go moving forward.
ABT-199 is a selective Bcl-2 inhibitor that induces cell death. In phase I trials the data were impressive in CLL and MCL, and there is even a good signal in there for it in larger lymphomas. Although it is too early to call, I think it is going to be an active agent that we should watch very closely.
What about the anti-CD20 agent obinutuzumab?Obinutuzumab was recently approved for the treatment of CLL, and it seems to be more effective than rituximab in some subsets of B-cell lymphomas. Now we have to go through multiple randomized trials to determine, in a more scientific way, whether substituting rituximab with obinutuzumab would be more beneficial in these diseases that have an indication for rituximab. There is a good chance to build up on the success in CLL and potentially change the treatment paradigm for other B-cell lymphomas by replacing rituximab with obinutuzumab.
Please discuss your research on brentuximab vedotin that was recently published in The Lancet Oncology.The antibody-drug conjugate brentuximab vedotin targets CD-30. It is approved by the FDA for patients with relapsed classical Hodgkin lymphoma and anaplastic large cell lymphoma. In the relapse setting, single-agent activity for brentuximab vedotin exceeds 75% in Hodgkin lymphoma and 86% in anaplastic large cell lymphoma. This is remarkable single-agent activity, so it makes a lot of sense to take a highly effective agent in a relapse setting and move it upfront and combine it with effective regimens.
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