Efficacy and Safety of Polatuzumab Vedotin in Follicular Lymphoma: A Systematic Review of Clinical Trials

Introduction:

Polatuzumab vedotin (Pola) is a humanized anti-CD79b monoclonal antibody linked with antimitotic agent monomethyl auristatin E. On internalization, the linker is cleaved, and antimitotic activity inhibits the cell division and growth of cancer cells. Pola is tested in multiple combinations in relapsed/refractory (RR) follicular lymphoma (FL) in recent years. In this systematic study, we will assess the efficacy and safety of Pola based combinations in RR FL.

Methods:

A literature search was performed on PubMed with keywords, “Polatuzumab vendotin” and “lymphoma” from the inception of data till 07/01/2023. PRISMA guidelines were followed while conducting this systematic review. We reviewed 160 articles and included 1 randomized clinical trial (RCT, N=41), and 4 non-randomized clinical trials (nRCT, N=163) based on inclusion criteria. Data was extracted for complete response (CR), partial response (PR), overall response (ORR), progression free survival (PFS), overall survival (OS) and ≥grade 3 side effects.

Results:

In 5 trials (N=204), 13 patients with Pola + atezolizumab (Ate) + obinutuzumab (Obi), 49 patients with Pola + Obi + venetoclax (Ven), 39 patients with Pola + Obi, 62 with Pola + Obi + lenalidomide (Len), and 20 patients with Pola + rituximab (Rit). In an RCT by Morschhauser et al. (N=41), Pola + Rit was compared with pinatuzumab vedotin (Pina) + Rit. ORR, CR, PR, and mPFS was 70%, 45%, 25%, and 15.3 months, respectively with Pola + Rit, as compared to 62%, 5%, 57%, and 12.7 months, respectively, with Pina + Rit. In a trial by Philips et al. (N=39), ORR, CR, PR, and mPFS were 67%, 36%, 31%, and 11.5 months, respectively. In 3 nRCTs (N=124), three drug regimens were used with Pola and Obi as backbone. ORR, CR, PR were 50%-83%, 20%-61%, and 20%-39%. Table 1. ≥ Grade 3 hematological and non-hematological side effects are given in table 1.

Conclusion:

Pola was well tolerated by most of the patients with FL alone or in combination with Obi, Rit, Len, Ven. Pola had relatively better response and survival rates as compared to Pina in combination with Rit. In early phase clinical trials, three drug regimens of Pola and Obi with Ven, and Len were effective in the treatment of heavily pretreated follicular lymphoma. In an early phase trial, Pola + Obi + Ate had limited efficacy in FL with safety concerns. More randomized double blind multicenter phase III clinical trials are needed to confirm these results.