Abstract: Polatuzumab vedotin is an anti-CD79b antibody conjugated to monomethyl auristatin E that has shown significant clinical activity in follicular and diffuse large B-cell lymphoma (DLBCL) and is currently FDA-approved in combination with bendamustine and rituximab for patients with relapsed/refractory DLBCL. This review article summarizes data from clinical trials of polatuzumab and discusses its current role and future directions in the treatment of patients with B-cell non-Hodgkin lymphoma.
Methods: We conducted a literature search in PubMed and Google Scholar from inception to January 2020, using the following terms: polatuzumab and CD79. We also reviewed the package insert and available abstracts and posters presented at national and international meetings.
Keywords: CD79, antibody-drug conjugate, polatuzumab, clinical trials, novel
Antibody-drug conjugates (ADCs) are monoclonal antibodies conjugated to cytotoxic payloads and directed toward tumor-associated antigens. Such a strategy combines the high selectivity and favorable pharmacokinetic profile of monoclonal antibodies with the high antitumor potency of the cytotoxic payload.
Polatuzumab vedotin (POLIVY™, Genentech) (pola) is an ADC consisting of a humanized anti-CD79b monoclonal antibody covalently attached via a protease-cleavable linker to monomethyl auristatin E (MMAE), a microtubule-disrupting antimitotic agent (Figure 1).1 Pola carries an average of 3.5 molecules of MMAE for each anti-CD79b antibody molecule. Once internalized, the linker is cleaved and MMAE is released resulting in microtubule network disruption and inhibition of cell division and growth. In June 2019, the US Food and Drug Administration (FDA) approved pola in combination with bendamustine and rituximab (BR) for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) after at least two prior therapies. Pola has also shown significant clinical activity in patients with follicular lymphoma (FL). Several other ADCs have proven to be effective in hematologic malignancies, with brentuximab vedotin (anti-CD30), inotuzumab ozogamicin (anti-CD22), and moxetumomab pasudotox (anti-CD22) currently approved by the FDA for use in lymphoid malignancies, while many others are being developed or tested in clinical trials.
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