ESMO Guideline for Mantle Cell Lymphoma

An Expert Interview With Martin Dreyling, MD, PhD

Martin H. Dreyling, MD, PhD; Linda Brookes, MSc

Disclosures

September 25, 2014

In This Article

All Cases of MCL Can Now Be Identified

Medscape: There are still a number of unresolved issues in the clinical management of MCL. Will the new guidelines address any of these?

Prof Dreyling: About 15 years ago, when we started our first randomized controlled trial in MCL,[4] the reviewers of the protocol said that we couldn't do the study because there was no standard of care in MCL. Fortunately, this situation has changed, and although there are still a lot of open questions in MCL, there are now many answers as well, because some of the problems have been addressed.

The first issue that has been solved—in fact the first question that we face as a clinician—is how to diagnose MCL. We know that on the basis of morphology alone, we can only correctly identify one third of cases. Now we can identify essentially all cases of MCL on the basis of cyclin D1 overexpression or identification of chromosomal translocation t(11;14) (q13;q32).[4] We gained a good understanding of the heterogenous features of MCL: There are indolent clinical courses, typical cases with initial high response rate but quick relapses, and the blastoid variant, which has a very poor prognosis. We also identified the underlying molecular alterations of these variants.[5,6] For example, indolent cases have the t(11;14) translocation only but no additional genomic alterations, whereas p53 mutations and p16 deletions are associated with the more aggressive forms of MCL, and these cases have a very poor prognosis regardless of what kind of therapy is applied.

Medscape: What do you recommend in regard to risk stratification?

Prof Dreyling: Our first recommendation is that when you decide to start treatment in a patient, you need to know their MCL International Prognostic Index (MIPI).[7] Second, the Ki-67 proliferative index should be considered, also outside of clinical trials, as a crucial prognostic indicator of long-term outcome.

Medscape: It's sometimes difficult to make a diagnosis of indolent MCL. How do the guidelines address this issue?

Prof Dreyling: The characterization of indolent MCL is an important point of the guidelines. We agreed that it is difficult to reliably identify. So far there is no black-and-white marker that defines this subpopulation, but we recommend what I believe is an important guideline: If you suspect an indolent behavior, an initial watch-and-wait period with the patient under close observation is appropriate.

Medscape: Can indolent MCL be recognized by a presentation similar to that of chronic lymphocytic leukemia (CLL), with high-normal lactate dehydrogenase (LDH) and a moderate lymphocytosis?

Prof Dreyling: Yes and no. We all know patients who have more indolent features similar to CLL. Historically, about 30 years ago, these cases were called atypical CLL. At that time they were seen as the patients who had poor prognosis compared to patients with CLL, but in fact they have a better outcome than that in classic MCL. On the other hand, the leukocyte count is a poor prognosis marker in the MIPI, and that again has been confirmed by all major series. So it is a kind of "catch-22": Probably 60% of these CLL-like cases are indolent ones, but a subset, another 40%, represents a poor-prognosis patient population. That is why it is so challenging to individualize treatment in MCL on the basis of the individual risk score.

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