Case 2: Frontline Treatments for CLL With Del(17p)

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Anthony Mato, MD, MSCE:Maybe 1 way to look at this would be to talk about what those options are. And are there data available frontline for patients with the deletion 17p? That may be the best way to try to decide how to select.

Shuo Ma, MD, PhD:In the first patient we discussed, we talked a lot about ibrutinib in therapy, which can apply for this patient as well. We didn’t get a chance to touch on the other treatment options. One of the very appealing to treatment options that has recently emerged is venetoclax-based therapy. In contrast to ibrutinib, which is continuous treatment, venetoclax treatment has been shown that you can use it as a time-limited therapy.

The frontline data came from the CLL14 study, which is comparing—again, they’re choosing the chlorambucil plus obinutuzumab as the control arm, and the experimental arm is the venetoclax plus obinutuzumab.

In this arm, patients were actually treated with obinutuzumab for the first 6 months. The first cycles were leading with the obinutuzumab alone to debulk the tumor in order to reduce the risk of tumor lysis, especially with venetoclax. Venetoclax is introduced after the first 3 weeks of treatment, and then the patient will go through the standard 5-week dose ramp-up to go up to 400 mg. They will continue the treatment for a total of 12 months, and our patient will stop treatment at that point.

One-to-one randomization for 432 patients total, the median age at the patient is 72 for the venetoclax-obinutuzumab arm and 78 for the chlorambucil-obinutuzumab arm.

Most patients have some comorbid conditions. The primary end point is progression-free survival. This study has demonstrated that venetoclax plus obinutuzumab has a significantly longer progression-free survival compared with chlorambucil-obinutuzumab, where the hazard ratio is 0.33. The most striking thing is looking at the response rate. You can see that the venetoclax plus obinutuzumab actually has a very high overall response rate of 85%, but also the complete response rate is almost 50%. That is compared with only 23% with a chlorambucil-obinutuzumab combination.

The most important data come from the MRD, or minimal residual disease. MRD in this study is defined by flow cytometry for less than 10^-4cells detectable, either in peripheral blood or in a bone marrow.

In the peripheral blood the MRD-negative rate in the venetoclax-obinutuzumab combination is actually as high as 76%.

We know that with the ibrutinib-based treatment, it’s very difficult to achieve even a complete response. To achieve an MRD-negative response is almost nearly impossible—very rare. Apparently with the venetoclax-based therapy, really able to achieve this very deep response, and probably that’s why a patient can stop treatment and remain in remission for quite a long time.

Transcript edited for clarity.