Sameer A. Parikh, MD
The therapeutic armamentarium of chronic lymphocytic leukemia (CLL) has quickly expanded over the years beyond the standard fludarabine, cyclophosphamide, and rituximab (FCR) regimen to include promising targeted options, such as ibrutinib (Imbruvica), idelalisib (Zydelig), and venetoclax (Venclexta).
How physicians can decide on an agent and when to administer it can be based on the CLL International Prognostic Index (IPI), a scoring system that tests for the common prognostic factors of the disease. Results of a study published in The Lancet Oncology
demonstrated that the CLL-IPI allows for more targeted management of patients with CLL in both clinical practice and in trials exploring novel agents.
“For all your patients with CLL, try to obtain the CLL-IPI because that is now becoming an effective tool for our ability to prognosticate these patients and predict when they are going to get treatment,” said Sameer A. Parikh, MD.
Parikh, an assistant professor of medicine at Mayo Clinic, discussed how the IPI has assisted physicians with their patients who have CLL, the optimal sequencing of therapies, and other emerging molecular targets in an interview during the 2017 OncLive®
State of the Science Summit on Hematologic Malignancies.
OncLive: Please provide an overview of your lecture on CLL.
: I broke down the talk into several different parts. The first part was prognosis in patients with CLL who are newly diagnosed and don’t yet meet indication for therapy. Roughly two-thirds of all our patients at the time of diagnosis are early stage, asymptomatic, and do not need any treatment. There are a myriad of prognostic markers available in this particular field to be able to tell our patients when they are likely to need treatment.
One of the most important contributions to the literature has been the development of the so- called IPI, or the CLL International Prognostic Index. This combines 5 different factors, including age, clinical stage, TP53
mutation status, IGVH
mutation status, and serum β2-microglobulin concentration. This will allow us to prognosticate when these patients are going to need therapy. We try do clearly obtain this for all of our patients, [especially for those who are] newly diagnosed and don’t need treatment yet.
How do you choose a frontline therapy for your patients?
Frontline therapy in CLL has evolved over the years and, with the introduction of novel targeted therapies, this has changed quite a bit. One of the most important [approaches] that has come out is targeting the BCR pathway, [with treatments such as] ibrutinib, idelalisib, and BCL-2 antagonists, including venetoclax. There are several major phase III clinical trials that have compared conventional cytotoxic chemotherapy—including FCR and bendamustine and rituximab (Rituxan; BR)—to novel agents. The results of these are all pending.
We tried to individualize treatment for our patients based on what their risk stratification is, and [if there] is evidence of 17p deletion—then, cytotoxic chemoimmunotherapy is not really considered a good option for these patients. We try to move to some of the other novel therapies, such as ibrutinib, because there are excellent data for that medication in those groups of patients.
If the patient is young with mutated IGVH
status, there are now data that indicate long-term remissions from FCR therapy and so we try to use a particular combination in those select groups of patients. The clear majority of our patients are older, have a number of comorbidities and, in that area, there are data to suggest that combination therapy of chlorambucil and obinutuzumab (Gazyva) leads to excellent progression-free survival (PFS) and overall survival compared with chlorambucil alone and chlorambucil and rituximab. That is a very good treatment option.
The most recent data in the upfront setting was the RESONATE-2 trial, which compared chlorambucil with ibrutinib and showed that ibrutinib had a very good PFS. The field of treatment has expanded considerably and now, thankfully, we have many treatment options to offer our patients.
With the emergence of newer agents being developed and moving along the pipeline, are there any concerns with sequencing?
That is an excellent question. Sequencing is a very important question; we all have seen data that patients who received cytotoxic chemoimmunotherapy with FCR or BR evolved and developed more resistance in their disease process, with acquisition of other genetic markers that are harder to treat. Therefore, sequencing is a very important thing in the planning of CLL therapy for our patients.