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Dr. John Seymour on IgHV Mutational Status

In science and medicine, information is constantly changing and may become out-of-date as new data emerge. All articles and interviews are informational only, should never be considered medical advice, and should never be acted on without review with your health care team.

In this video, Dr. Brian Koffman interviewed Dr. John Seymour, Director of the Department of Hematology at Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Melbourne, Australia. They discussed our latest learnings on how IgHV mutational status affects treatment outcomes.

What is IgHV?

Certain predictive biomarkers allow us to make a reasonable prediction as to which therapies offer the best chance of success. Therefore, CLL Society recommends everyone get tested before starting treatment (see our Test Before Treat one-pager). One of these biomarkers is the mutational status of immunoglobulin heavy chain (IgHV or IgVH). Patients with a mutated IgHV do much better with chemoimmunotherapy than those with unmutated IGHV. In addition, CLL with mutated IGHV tends to grow slower than CLL with unmutated IgHV. Mutated IgHV is also correlated with better progression-free survival and overall survival.

How have targeted therapies changed our understanding of IgHV?

Recently, a number of studies have found that when patients with mutated or unmutated IgHV are treated with targeted therapies, the difference in outcomes has largely been eliminated. Continuous therapies such as BTK inhibitors dramatically reduce the difference in outcomes between mutated and unmutated IgHV. The remissions are similar when patients are treated with limited-duration venetoclax plus an anti-CD20 antibody such as rituximab. Still, CLL with unmutated IgHV tends to reappear more quickly. When patients are treated with a limited-duration combination of ibrutinib plus venetoclax, there does not appear to be a difference in outcomes between mutated and unmutated IgHV; many of these trials are still ongoing.

What does that mean in the long term?

Our understanding of how IgHV mutational status affects patient outcomes is evolving as new therapies are being tested. Thus far, it appears that patients with mutated or unmutated IgHV largely respond equally well to initial treatments with targeted therapies. However, there are some subtle differences depending on which agent is used. It’s still early in our real-world use of these new medications to grasp the durability of responses. What happens when patients relapse and need to be retreated remains to be seen.

Links and Resources:

Watch the interview here:

ASH 2022: Dr. John Seymour on Mutated vs. Unmutated IgVH CLL as an Indication of High-Risk Disease

Take care of yourself first.

Ann Liu, PhD