Polatuzumab vedotin: an investigational anti-CD79b antibody drug conjugate for the treatment of diffuse large B-cell lymphoma

ABSTRACT

Introduction

New agents for managing B-cell non-Hodgkin lymphomas (NHLs) are needed, particularly for high-risk and relapsed or refractory patients. Antibody–drug conjugates (ADCs) provide targeted drug delivery to tumors with a broaden therapeutic index of cytotoxic agent, reducing their systemic toxicity while increasing intracellular concentrations. Polatuzumab vedotin, an anti-CD79b conjugated to the microtubule inhibitor monomethyl auristatin E (MMAE) raises particular interest.

Areas covered

We discuss here polatuzumab vedotin development, challenges of designing a successful ADC, preclinical studies and recent trials, leading to FDA approval and the ongoing phase III POLARIX trial.

Expert opinion

Clinical data from early studies hold promises for polatuzumab vedotin in association with rituximab-bendamustine in relapsed or refractory (R/R) DLBCL and other combinations are investigated in this setting. In first line, with rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHP), promising results lead to develop the phase III POLARIX trial that may represent a new advance for untreated patients. If dosing and scheduling are adequately managed to avoid peripheral neuropathy risk, polatuzumab vedotin might become a key component of DLBCL therapeutic management. This antibody drug conjugate also offers new opportunities of combination with non-cytotoxic agents or immunological interventions that might reshape the treatment of DLBCL in the future.

KEYWORDS:

• Antibody-drug conjugates
• CD79a
• diffuse large B-cell lymphoma
• polatuzumab vedotin

Article highlights

• ADC enable targeted delivery of cytotoxic drug to neoplastic cells, reducing systemic toxicity

• Several ADC are raising great interest in the treatment of hematological malignancies, targeting CD30, CD22, and CD79b

• Polatuzumab vedotin, an anti-CD79b conjugated to MMAE, is the third ADC approved by the FDA and the first one for use in DLBCL patients

• Recent phase Ib/II data of polatuzumab vedotin in combination with different agents indicated high efficacy in R/R DLBCL and in previously untreated patients with manageable hematological and neurological toxicity

• Ongoing phase III POLARIX trial is challenging the standard of care R-CHOP with polatuzumab vedotin replacing vincristine (Pola-R-CHP) as first line treatment for DLBCL patients.

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Declaration of interest

G Salles has received financial compensations for advisory board or consulting roles from Abbvie, Autolus, Celgene, Genmab, Gilead, Epizyme, Janssen, Karyopharm, Kite, Merck, Morphosys, Novartis, Roche, Servier, and Takeda and for participation in educational events by Abbvie, Amgen, Celgene, Gilead, Janssen, Kite, Morphosys, Novartis, Roche, Servier, and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.