Antibody Drug Conjugate Yields Mixed Results in Follicular Lymphoma

Follicular lymphoma remains an incurable subtype, and it is especially difficult to treat in patients whose disease has relapsed or become refractory to treatment.

Finding new ways to overcome the refractory aspect has become a research priority.

Study results were presented at last weekend's annual meeting of the American Society of Clinical Oncology that looked at applying an exciting new technology-- the antibody drug conjugate-- to patients with relapsed or refractory follicular non-Hodgkin's lymphoma.

Antibody Drug Conjugates (ADC)

The most well-known antibody drug conjugate is brentuximab vedotin, or Adcetris, which is used in the treatment of people with Hodgkin's lymphoma or anaplastic large cell lymphoma. Antibody drug conjugates combine the targeted therapy of an antibody with a known cancer-killing drug. Contrary to chemotherapy, they are designed to do as little damage as possible to healthy cells in the body while doing as much damage as possible to cancer cells.

Whereas Adcetris is an anti-CD30 antibody drug conjugate, polatuzumab vedotin is an anti-CD79b antibody-drug conjugate, meaning it locates cancerous B-cells by using a different cell surface target (the CD79b) than Adcetris. According to Ranjana H. Advani, MD, professor of lymphoma at Stanford University, who gave the presentation, CD79b is "a component of the B-cell receptor and is expressed in nearly all B-cell malignancies."

This ought to make it an appealing target for treatment.

One of the problems researchers faced early on was the fact that polatuzumab vedotin was proving to be too toxic at the otherwise optimal dosage of 2.4 mg/kg. Therefore the point of this latest trial was to lower the dosage of polatuzumab vedotin but keep the effectiveness of it in killing cancer in patients with relapsed or refractory follicular lymphoma by adding the well-known drug rituximab to the equation.

In this phase two trial, researchers divided a group of 45 qualified patients into two arms: twenty patients would receive 375 mg/m2 rituximab with 1.8 mg/kg polatuzumab vedotin every three weeks until the occurrence of an unacceptable toxicity; while 25 patients would receive 375 mg/m2 rituximab with 2.4 mg/kg polatuzumab vedotin every three weeks until the occurrence of an unacceptable toxicity.

Researchers compared data at the completion of polatuzumab vedotin treatment with data after eight treatment cycles.

Median follow-up was 14 months for the 2.4-mg/kg cohort and 8 months for the 1.8-mg/kg cohort.

Between the two groups, the overall response rate to this treatment was nearly the same: 76 percent in the higher dose group and 75 percent in the lower dose group.

Complete response rates were different, however. In the higher-dose group, the complete response rate was 32 percent, compared to just ten percent in the lower dose group. That was after eight treatment cycles. After all treatment cycles, the complete response rate in the first group went up to 44 percent but did not change in the lower dose group.

Unfortunately, the rate of discontinuation of treatment was higher in the higher dose group than in the lower dose group, likely because of the occurrence of more grade 3/4 adverse events-- in other words, really bad side effects.

So while adding rituximab to the higher dose of polatuzumab vedotin achieved more complete responses, it also led to more adverse events and more people quitting treatment, leading this research team to conclude that the 1.8 dose is the clinically meaningful treatment option, and that at this point, more work is needed to figure out how to make this a better treatment option for patients with relapsed or refractory follicular lymphoma.

Source: ASCO