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ASH 2017: Dr. Tam on the Prognostic Value of IVGH mutation status in CLL (chronic lymphocytic leukemia)

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Dr. Constantine Tam of Peter MacCallum Cancer Center, Melbourne, Australia has contributed important research for chronic lymphocytic leukemia patients while working at PeterMac in Australia and MD Anderson in Texas.

I interviewed Dr. Tam at ASH 2017 in Atlanta, Georgia about his research into an important prognostic and predictive factor, namely immunoglobulin heavy-chain variable region gene mutational status or more commonly IVGH mutation status.

Take Away Points:

  • IVGH mutation is a measure of the maturity the particular B cell clone that is the source of our CLL.
  • Mutated cells are more mature and less aggressive and less resistant to chemo-immunotherapy.
  • This is particularly important in predicting response to one of the most common chemo-immunotherapies, FCR (fludarabine, cyclophosphamide and rituximab) that may be curative for some patients with chronic lymphocytic leukemia.
  • The standard cut point in CLL for deciding whether IVGH is mutated is whether 2% or more of the heavy chain of the IVGH had been modified or mutated.
  • Tam’s research demonstrates for the first time that is an arbitrary line and that the greater the mutation, the better the prognosis for those treated with FCR.
  • This prognostic significance does not apply to CLL patients treated with ibrutinib.

Conclusions:

For a small select group of young fit CLL patients, FCR offers the possibility of very durable remissions (more than 13 years) that are starting to look as if the leukemia has been cured.

Knowing your prognostic markers, especially IVGH mutation status, FISH, and p53 are critical in deciding what therapy is best. Knowing the percent of mutation of the heavy chain gives even more helpful information

That is why we urge all patients to “Test Before Treat”.

For the basic information of prognostic testing in CLL, please see Prognostic Factors in CLL by Dr. Kamdar.

You can view my ASH 2017 interview with Dr. Tam below or read the transcript here.

You can access more about the research in the abstract here: Absolute Percent Deviation of IGHV Mutation As a Continuum Is Prognostically Relevant in Patients with CLL.

Stay strong.

We are all in this together.

Brian Koffman MD  5/7/18