ASH 2017 – Dr. Stamatopoulos on Stereotypic Immunoglobulins in CLL (chronic lymphocytic leukemia)

Dr. Kostas Stamatopoulos has done important basic CLL research, set necessary lab standards and been a strong patient advocate from beautiful Thessalonica, Greece.

I had a chance to catch up with my friend in Atlanta for ASH 2017, where he explains the complexities of our increasingly nuanced understanding of prognostics in chronic lymphocytic leukemia.

Take Away Points:

• We have known for decades that patients with mutated IVGH genes do better than those who are unmutated.
• This is likely because mutated CLL are more mature as the IVGH has been changed to recognize certain threats. Unmutated cells are less developed and often are more aggressive.
• We now know that there is not a strict cut off of 2% that predicts outcomes. Dr. Tam discusses this in more detail here. Briefly, his research showed that the higher percentage of IVGH that is mutated, the better the odds for progression-free survival.
• This does not apply to novel agents.
• We also now know that the majority of CLL patients treated with frontline FCR that do well for a very long time (at least 13 years) are those with mutated IVGH using the standard 2% cut point.
• Stamatopoulos’ team helps explain why there is such a significant variability for mutated patient in how indolent or aggressive is the course of their CLL.
• Their research found that certain patterns of gene mutation that were repeated exactly or near-exactly in mutated IVGH form recognizable subsets of stereotypic mutations that were predictive of different outcomes, including more aggressive CLL compared to what would typically be expected based on only looking at whether the cells was mutated
• These predictive patterns can be tested for, though it not commonly done.

Summary:

Little is black and white in CLL and it turns out that prognostic testing is complicated and nuanced. As always, the more information we have, the better choices we can make.

Here is a link to my interview with Dr. Stamatopoulos or you can read the transcript here.

This is a complicated topic: Here are links to a few relevant ASH abstracts for those who want to read more.

CLL-Specific B Cell Receptor Immunoglobulin Stereotypes Are Very Infrequent in Low Count Monoclonal B Cell Lymphocytosis: Implications for Disease Ontogeny

CLL Stereotyped Subset #4 Igs Acquire Binding to Viable B Lymphocyte Surfaces By Somatic Mutations, Isotype Class Switching, and with the Prerequisite of IG Self-Association

Patients with Chronic Lymphocytic Leukemia Belonging to the B-Cell Receptor Stereotypy Subset #2 Have Long Progression Free Survival after Chemo- or Chemoimmunotherapy in the HOVON68 Trial

Brian Koffman, MD 5/29/18