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Polatuzumab vedotin is a CD79b antibody conjugate indicated to treat different types of large B-cell lymphoma.
Polatuzumab vedotin is a CD79b antibody conjugate indicated to treat different types of large B-cell lymphoma.
Polatuzumab vedotin is an antibody-drug conjugate consisting of a CD79b-directed antibody, a microtubule-disrupting agent called monomethyl auristatin E (MMAE), and a cleavable linker that holds the components together. CD79 is a heterodimer composed of CD79a and CD79b. Responsible for signal transduction, CD79 forms a complex with the B cell receptor (BCR) and is almost exclusively expressed on B cells, including malignant B cells. Most importantly, CD79b gained increasing attention as a promising therapeutic target as it plays an essential role in BCR expression, transport, and functions such as B cell proliferation and differentiation. Once the antibody component binds to CD79b, polatuzumab vedotin is internalized, and lysosomal proteases cleave the linker to release MMAE in the cell. MMAE is a microtubule-disrupting anti-mitotic agent that exerts cytotoxic effects against malignant B cells. It binds to microtubules, inhibits mitosis by interfering with tubulin and tubulin polymerization, and induces apoptosis in dividing B cells.
Polatuzumab vedotin is used in combination with bendamustine and rituximab to treat adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified, after at least two prior therapies. In Canada, this indication is approved for patients who are not eligible for autologous stem cell transplant and have received at least one prior therapy. Polatuzumab vedotin is also used in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) to treat adult patients with previously untreated large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), high-grade B-cell lymphoma, Epstein-Barr virus-positive (EBV+) DLBCL NOS, and T-cell/histiocyte rich LBCL.
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