Polatuzumab Vedotin: Review Spotlights Its Use, Promise in DLBCL

A recent Haematologica review of studies evaluating the use of polatuzumab vedotin, an antibody-drug conjugate (ADC), in diffuse large B-cell lymphoma (DLBCL)provides insight and data drawn from recent research.¹ The outlook is decidedly promising, andpolatuzumab vedotin’s role “will undoubtedly rapidly evolve,” the authors declared. They also summarized ongoing trials with the agent.

Many questions remain about howpolatuzumab vedotin will be used in various hematologic oncology settings in the future,but what is evident now, the authors stated, is that this ADC can improve outcomes in patients with DLBCL compared withprevious standard treatment regimens. What’s more, the toxicities seen most frequently with polatuzumab vedotin—the hematologic and neurologic adverse events that are related to microtubule inhibition bymonomethyl auristatin E—are relatively easy to manage in routine practice.

The Disease and the Drug

The antibody-drug conjugate polatuzumab vedotin is showing itself to be beneficial in the relapse setting of diffuse large B-cell lymphoma | Image Credit: David A Litman-stock.adobe.com

DLBCL is the most frequently diagnosed lymphoma. Patient outcomes, including cures, have improved over time, especially since the introduction of R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine [Oncovin], and prednisone).² When R-CHOP does not result in a cure, polatuzumab vedotin may prove invaluable.³ The authors’ review shows that in the relapse setting, combinations of polatuzumab vedotin with cytotoxic agents or bispecific antibodies are clearly effective, they declared.

The relapse setting presents quite a challenge, both in percentage of patients affected and disease tenacity. After R-CHOP or other frontline treatment, up to 40% of patients with DLBCL are either refractory to it or experience relapse. Prior to the introduction of chimeric antigen receptor T-cell therapy (CAR T), such patients usually survived 6 to 12 months.

Even among patients who can and do opt for CAR T or autologous stem cell transplant, about half still experience further disease progression. Of those who need but are unable to access CAR T or transplant, the authors noted that about 80% will die of progressive lymphoma or complications from subsequent lines of therapy.

Polatuzumab vedotin is composed of an anti-CD79b antibody conjugated to monomethyl auristatin E, and based on the results of studies that are among those discussed in the review article, many countries have approved polatuzumab vedotin for patients with relapsed/refractory DLBCL and, in some cases, previously untreated DLBCL.

For instance, in the frontline setting, the important phase 3 POLARIX trial (NCT03274492) compared with polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) with standard R-CHOP; improved progression-free survival (PFS) was the primary end point. Indeed, treatment with pola-R-CHP significantly improved 2-year PFS (76.7%) vs standard R-CHOP (70.2%). At a median follow-up of 28.2 months, the risk of progression, relapse, or death was lower in the pola-R-CHP group vs the R-CHOP group (HR, 0.73; P = .02).

In a phase 2 trial, combining polatuzumab vedotin with standard rituximab and bendamustine (BR) in patients with relapsed/refractory DLBCL achieved a “remarkable improvement” over BR in terms of complete response (CR) rate, the study’s primary end point, and overall survival (OS). The CR rate was 40% in the pola-BR group vs 18% in the BR-alone group (P = .026). After a median follow-up of 22.3 months, PFS, OS, and duration of response in the pola-BR vs BR-alone groups were 9.5 and 3.7 months (P < .001), 12.4 and 4.7 months (P < .001), and 12.6 and 7.7 months, respectively.

A major benefit of polatuzumab vedotin is that its target protein, CD79b, is expressed on the surface of mature B-cell lymphomas, including more than 95% of all cases of DLBCL, explained the authors. CD79b is part of the B-cell receptor complex and is involved in signal transmission.

References

1. Ghione P, Salles G. Spotlight on polatuzumab vedotin: new standards for diffuse large B-cell lymphoma? Haematologica. Published online May 30, 2024. doi:10.3324/haematol.2022.282362

2. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared withCHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med.2002;346(4):235-242. doi:10.1056/NEJMoa011795

3. Dornan D, Bennett F, Chen Y, et al. Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma.Blood. 2009;114(13):2721-2729. doi:10.1182/blood-2009-02-205500