Expert Looks to Genetic Testing for Next Leap in MCL

Gina Columbus @ginacolumbusonc
Published Online: Monday, May 08, 2017

Grzegorz S. Nowakowski, MD
Researchers are conducting gene expression profiling studies to explore potential prognostic factors of developing mantle cell lymphoma (MCL), a challenging issue oncologists are currently facing, according to Grzegorz S. Nowakowski, MD.

Results of a study presented at the 2016 ASCO Annual Meeting demonstrated early promise with the NanoString platform, using the Affymetrix U133 microarray gene expression with the MCL55 assay, to measure the proliferation signature in RNA that is derived from formalin-fixed paraffin-embedded tissue.

Results showed that the novel MCL55 assay, which contains a 16-gene proliferation signature, yielded gene expression of sufficient quality to assign a score and risk group in 98% of the archival paraffin-embedded tissue from the overall 110 patients, assigning patients to high-, intermediate-, and low-risk groups. The median overall survival (OS) differed among the high-, intermediate-, and low-risk groups at 1.1, 2.6, and 8.6 years, respectively (P <.001).

In an intention-to-treat population of 59 of these patients with an autologous stem cell transplant to consolidate response, the median OS differed again across the high-, intermediate-, and low-risk groups at 1.4 years, 5.9 years, and not reached, respectively (P <.001). The findings suggest that the MCL55 assay for paraffin-embedded tissue can use the proliferation signature to define groups of patients with MCL with different OS.

In an interview during the 2017 OncLive® State of the Science Summit on Hematologic Malignancies, Nowakowski, an assistant professor of Medicine at Mayo Clinic, discussed the current work being conducted to determine prognostic factors of MCL and what other challenges still lie ahead.

OncLive: At this point in time, what are some of the key factors involved in choosing a first-line, second-line, and beyond treatment for patients with MCL?

Nowakowski: One factor which I am not taking into consideration, but I would like to, is biological heterogeneity of the disease. We know that some of the patients have relatively indolent disease progressing over the years, while other patients have rapidly progressive disease. The vast majority of patients come right in the middle. It would be nice to have a biologic prognostic factor to predict the clinical course of those patients, because this would help us in selecting the most appropriate therapy for them.

There is such an attempt being made: the NanoString platform [with the MCL55 assay] which uses gene expression profiling from paraffin-embedded tissue. There was something presented at the 2016 ASCO Annual Meeting, which showed the specific signatures that might be predicting the outcome of these patients. Hopefully, at some point, we will have it in the clinic and that is what I would really like to use. 

What I use right now is patient performance status and age. Age is an important factor; traditionally younger patients who are fit are treated with more aggressive chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation. In elderly patients, it comes down to less intensive options. Bendamustine-rituximab is frequently employed. It has shown better progression-free survival than therapy with R-CHOP in a randomized study; it is well tolerated and is very commonly used in this setting. 

A nonchemotherapy-based backbone with lenalidomide and rituximab is sometimes used, as well. Sometimes patients have a strong preference whether they want chemotherapy or a “pill-like” option; that is also taken into account with dose decisions.

What we really need though, over time, [are treatment decisions] based on biological prognostic factors, rather than just age and performance status. It would be interesting to compare those nonchemotherapy approaches against more of an aggressive approach used in younger patients. It may be that, in the future, combinations of targeted agents are much less toxic than intensive chemotherapy regimens with transplant, and could be as effective—if not more—than traditional cytotoxic intensive chemotherapy.  

Where is the field at currently with biomarker development? 

For a long time, we have been using perforation in the index of Ki-67, which is prognostic in this setting. However…right now, there is no evidence that high Ki-67 should necessarily guide the next selection of therapy. There are various studies addressing these issues.


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