Predictive Factors More Important in Relapsed/Refractory DLBCL--Dr. Randy Gascoyne's Interview at ICML 2015

Reproduced from Oncology Frontier

Randy Gascoyne, MD 

Research Director, 

BC Cancer Agency 

the University of British Columbia

Vancouver, BC Canada 

Taken at ICML 2015 

Oncology Frontier《肿瘤瞭望》：CNS progression is one of the lymphoma complications with poor prognosis, what kinds of predictive risk factors, prophylactic treatment available? 

Dr Randy Gascoyne: If we focus on the most common disease, diffuse large B-cell lymphoma， then there is a risk. It is not very high (about 3-4%) but when it happens it is devastating in terms of progression because it is very hard to treat.

We are starting to put together an idea of the factors in the diagnostic biopsy that predict for that outcome. There is a set of clinical criteria that have been developed by a German group that seems to work to a degree.

My colleagues and I in Vancouver have made the observation that the patients who show expression of a couple of proteins in their diagnostic biopsy (MYC and BCL-2) have a pretty significant heightened risk of CNS progression.

To recognize that is important but you wouldn't prophylactically treat those patients.

What you would do is consider the possibility of treating them in a different way upfront to prevent that as an outcome. If the patient has CNS involvement, then that would be treated, but in those where you find eventual predictors of relapse or progression in the CNS, that is a different consideration and needs to be approached in a different way. Not through CNS prophylaxis, but by treating them differently upfront to prevent the eventual clinical outcome.

New biological treatment for relapsed and refractory non-Hodgkin lymphoma

Dr Gascoyne: Focusing again on diffuse large B-cell lymphoma as the most common example, the standard of care globally is still the combination of rituximab and CHOP (R-CHOP). That will cure long-term 60% of patients.

The problem is that 35-40% are not cured through the approach. The key is not to develop novel therapies to be used in the relapsed/refractory setting, but to determine what the factors that allow us to predict they will be the ones to behave aggressively and fail and to determine that upfront.

If we can determine who they are at the very beginning, they can be offered these new therapies. The field has been moving towards what in addition to R-CHOP will improve outcomes.

This is where ibrutinib and lenalidomide are being tested. There are a number of new agents now in phase III clinical trials.

We will have to wait for the results of those before we can make decisions, but in an ideal world, if we can pick the bad responders at the point of initial diagnosis, we can offer them appropriate treatments if we know they are going to behave aggressively to prevent relapse or progression.

References:

1. [ICML2015] B细胞淋巴瘤的分子机制及治疗新主张——访加拿大不列颠哥伦比亚大学Randy D. Gascoyne教授 2015/7/6 18:02:32 © 肿瘤瞭望 Video

2. Perry AM et al MYC and BCL2 protein expression predicts survival in patients with diffuse large B-cell lymphoma treated with rituximab. Br J Haematol. 2014 May;165(3):382-91. doi: 10.1111/bjh.12763.

3. Sehn LH et al Diffuse large B-cell lymphoma: optimizing outcome in the context of clinical and biologic heterogeneity.Blood 015 Jan 1;125(1):22-32. doi: 10.1182/blood-2014-05-577189.

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