Targeting Non-Hodgkin Lymphoma

The molecularly targeted therapeutic polatuzumab vedotin-piiq is the first antibody-drug conjugate approved for treating diffuse large B-cell lymphoma.

The U.S. Food and Drug Administration (FDA) recently approved a new molecularly targeted therapeutic called polatuzumab vedotin-piiq (Polivy) for treating certain patients with the most common type of non-Hodgkin lymphoma, diffuse large B-cell lymphoma.

Polatuzumab vedotin-piiq is intended for use in combination with the cytotoxic chemotherapeutic bendamustine and the immunotherapeutic rituximab for treating adults who have diffuse large B-cell lymphoma that has not responded to or has relapsed after two other treatments.

Diffuse large B-cell lymphoma is a fast-growing, aggressive type of non-Hodgkin lymphoma. According to National Cancer Institute statistics, every year, there are 5.6 new cases of diffuse large B-cell lymphoma per 100,000 U.S. adults and 1.8 deaths.

As its name implies, diffuse large B-cell lymphoma arises in immune cells called B cells. Polatuzumab vedotin-piiq targets a protein called CD79b, which is found on the surface of immune cells called B cells, both normal B cells and those that become cancerous.

Polatuzumab vedotin-piiq is type of molecularly targeted therapeutic called an antibody-drug conjugate. Antibody-drug conjugates use an antibody to deliver an attached cytotoxic chemotherapeutic directly to the cancer cells with the antibody’s target on their surfaces. Once the antibody attaches to its target on the surface of a cancer cell, the antibody-drug conjugate is internalized by the cell. This leads to the cytotoxic chemotherapeutic being released from the antibody. Once free, it is toxic to the cancer cells, which ultimately die.

In the case of polatuzumab vedotin-piiq, the cytotoxic agent monomethyl auristatin E is attached to a CD79b-targeted antibody.

The approval of polatuzumab vedotin-piiq for treating diffuse large B-cell lymphoma was based on results from a phase Ib/II clinical trial that showed that adding the antibody-drug conjugate to bendamustine and rituximab increased the percentage of patient who had complete tumor shrinkage. Forty percent of patients who received all three of the anticancer therapeutics had complete tumor shrinkage compared with 18 percent of those who received only bendamustine and rituximab.

With this approval, polatuzumab vedotin-piiq became the first antibody-drug conjugate approved for treating patients with diffuse large B-cell lymphoma.