CD20 Monoclonal Antibody Dose Adjustment and MRD

Nitin Jain, MD: Samantha, we gave you venetoclax with rituximab. Recently, there is a new antibody called obinutuzumab which is another, new version of that antibody. Obinutuzumab is given at the same schedule as you received, and similar to your reactions with rituximab, it can cause significant reactions for patients. Specifically, obinutuzumab can cause reactions within the first one or two doses. The reason we didn’t put you on that antibody initially was because you were in the hospital with all these complications, specifically a blood clot, so we didn’t want to put you on an antibody that can potentially have some significant reactions. Therefore, we went with rituximab, which is gentler to get in, and has less of the reactions we typically see. You took the rituximab for a total of six months, correct?

Samantha Rine: That’s correct.

Nitin Jain, MD: Next, we did venetoclax for approximately one year.

Samantha Rine: That’s right.

Nitin Jain, MD: What testing were you having? When you were coming to see us, were we doing only blood tests, or were there bone marrows and CT [computed tomography] scans involved?

Samantha Rine: We did blood tests and a bone barrow test. In December, six months after the diagnosis, we did a bone marrow test, and then six months after that we did the blood tests, which were MRD [minimal residual disease]-negative. However, in the middle of treatment it was all blood work.

Nitin Jain, MD: Samantha mentioned neutropenia or low blood counts when we were giving venetoclax. Something patients who are taking venetoclax would know is that venetoclax can cause low blood counts, especially a low neutrophil count, which are the infection-fighting cells. Often, patients require their doses of venetoclax to be reduced. The standard dose of venetoclax is 400 mg once daily, and it is important to remember that this dose is started in a stepwise fashion. Typically, you start at 20 mg for one week, then you do 50 mg for one week, 100 mg for one week, 200 mg for one week, and then you reach 400 mg, which you then keep taking.

It is important that you have the stepwise approach. The reason is that venetoclax is a powerful drug that can cause tumor lysis syndrome. Venetoclax can kill cancer cells very rapidly, and it can create a lot of problems if it is not done in a stepwise manner. Once the patient is on a full dose of venetoclax, often they can have low blood counts. In that case, we have to cut back on the dose of venetoclax, so from 400 mg to 300 mg, or 200 mg, or 100 mg. Samantha, which dose were finally decreased to? Were you taking 100 mg or 200 mg of venetoclax?

Samantha Rine: Three hundred.

Nitin Jain, MD:I have patients where the dose could be reduced to 100 mg or 50 mg because they couldn’t tolerate that medication. However, there are a lot of patients who can tolerate the full dose. Many times, we do what is called growth factor support, called GCF, which is an injection that can boost the white blood cell count. Samantha, did we give you an injection to boost your white blood cell count?

Samantha Rine: I had that twice.

Nitin Jain, MD: That is somewhat common when we are using the venetoclax plus the antibody regimen that we have to consider giving to patients to keep their white blood cell count—specifically the neutrophil count, the infection-fighting cells—in the normal range. Samantha, congratulations for achieving MRD-negative remission! That is the best possible option we could have. I briefly wanted to comment on MRD because that is terminology you will hear from your doctors many times in CLL [chronic lymphocytic leukemia] centers. Doctors may be checking for MRD, and patients then want to know if they’re MRD-negative and how we are testing for MRD.

MRD stands for minimal residual disease, which is typically detected by a test called flow cytometry. It can be done either in the blood or the bone marrow. This test typically looks for one cancer cell in10,000 white blood cells. If it is present at that level, then that’s MRD-positive. If it is not present at that level, the test is negative, which means that you are MRD-negative. That analysis has been well established in the field of CLL. For patients who are on venetoclax-based therapies, one of my objectives as a doctor is to get them to MRD-negative remission. We know that for patients who achieve MRD-negative remission their response will typically last longer than patients who still are MRD-positive at the time we stop the therapy with venetoclax.

Transcript Edited for Clarity