At ASH (American Society of Hematology) Annual Conference in Atlanta in December, 2017, Dr. Ian Flinn from Sarah Cannon Cancer Institute, Nashville, TN presented very encouraging data on the combination of two of the most potent drugs used to treat chronic lymphocytic leukemia (CLL), venetoclax and obinutuzumab

Venetoclax (Venclexta) works with the cell’s energy source, the mitochondria, and blocks one of the props that CLL cell is highly dependent on to stay alive, namely BCL-2, leading to high rates of apoptosis or programmed cell death.

Obinutuzumab (Gazyva) is a new generation monoclonal antibody, a “better” antibody, that has been engineered to attack and kill CLL cells.

The combination has proven safe and effective in relapsed and refractory CLL patients. To view the abstract from ASH 2015, please click here.

This is my interview with Dr. Flinn on his presentation of the important results from a study in treatment-naïve chronic lymphocytic leukemia patients from ASH 2017.

Take Away Points:

One concern with venetoclax (V) is tumor lysis syndrome (TLS) where the cancer cells are killed so quickly that there are potentially life-threatening risks. Using obinutuzumab (O) first, there was no clinical evidence of TLS.

Every patient responded to this treatment.

>2/3 had complete remissions (CR).

Every patient achieved minimal residual disease negative or MRD negative ( <1 in 10,000 white blood cells that was a CLL cell) in the blood.

90% were still MRD negative 3 and 6 months later and as were more than 70% at 1 year.

75% were MRD negative in the bone marrow.

A partial remission did not lower the chances of being MRD negative.

Most patients stopped therapy after 1 year. At 18 months post-therapy, more than 90% of patients were still in remission.

Significant neutropenia (low neutrophil counts) was seen in about half of the patients, but infections were not increased.

Summary:

These results are remarkable and suggest a new pathway for the frontline treatment of CLL.

Deep and durable responses with no chemo and a finite course of therapy are pretty close to everything on my wish list for treating list for CLL.

What is still missing?

Just how long will these responses last? Only time will tell. That’s why we do research.

Why are some patients relapsing? Can we predict in advance who is at high risk to relapse and then modify our therapy for these high risk patients?

Will relapsing patients respond to another course of V+O?

Broader Implications:

There are also some much broader themes which this exciting research touches on:

Combinations are the future in CLL, maybe not for all patients, but certainly for many. I am encouraged by this trend in research.

These and other studies are casting doubt on the present definition of complete remissions (CR) that requires that all lymph nodes be 1.5 cm or less. This definition is being revisited and don’t be surprised if we see new guidelines in the next year. This makes good sense to me.

Summary:

This is very good news for treatment-naïve patients with impressive and durable responses with only one year of therapy. Hopefully, in the not too distant future, treatments such as V+O and other powerful non-chemo combinations will be available to many more patients both within and outside of clinical trials.

Here is a link to the abstract.

Please enjoy my interview with Dr. Flinn or read the transcript here.

Brian Koffman, MD 1/9/18

About the author

Todd Dennison