Polatuzumab Vedotin Plus R-CHP Emerges as Potential New Standard for Newly Diagnosed DLBCL

John M. Burke, MD

Polatuzumab vedotin-piiq (Polivy) plus rituximab (Rituxan), cyclophosphamide, doxorubicin, and prednisone (R-CHP; pola-R-CHP) showcased several benefits over R-CHOP (rituximab plus cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), and may represent a new standard option for this population, according to John M. Burke, MD.

Data from the phase 3 POLARIX trial (NCT03274492), which were presented during the 2021 ASH Annual Meeting, showed that pola-R-CHP resulted in a 27% reduction in the risk of disease progression or death vs R-CHOP. The 24-month progression-free survival (PFS) rate was 76.7% with the polatuzumab vedotin regimen vs 70.2% with R-CHOP, translating to an absolute difference of 6.5% (P < .02).¹

“We believe that [pola-R-CHP] may be a new option, or even a new standard, for patients with advanced-stage DLBCL,” Burke, who is the associate chair of the Hematology Research Program for US Oncology and a medical oncologist and hematologist at Rocky Mountain Cancer Centers, said. “That is what is [most] exciting about these findings.”

In an interview with OncLive^®, Burke further discussed the pivotal POLARIX trial in newly diagnosed DLBCL, highlighted the benefits derived with pola-R-CHP, and projected the next steps for the regimen.

OncLive^®: What inspired the launch of the phase 3 POLARIX trial examining pola-R-CHP?

Burke: The standard treatment for patients with [newly diagnosed] DLBCL has been the chemoimmunotherapy regimen R-CHOP. That standard was established a couple of decades ago, when it was shown that adding rituximab to CHOP chemotherapy improved outcomes for patients with this disease.

Since then, many attempts have been made to improve upon [the benefits provided by] R-CHOP. We know that R-CHOP cures about 60% of all patients with advanced-stage DLBCL, but that leaves 30% of patients who are not cured. We want to do better, and that has been the goal; however, trial after trial failed [to do this]—until now. This is the reason why we are all so excited about POLARIX.

What makes polatuzumab vedotin unique?

Polatuzumab vedotin is an antibody-drug conjugate; specifically, it is an antibody that binds to CD79b, which is a protein [found] on malignant B cells, and it is linked to a toxin. As such, [the agent] is a combination of an antibody and a drug. The antibody is delivering the drug to, and inside, the malignant cell, where the drug is then released and can kill the cell. An impressive study showed that when you add polatuzumab vedotin to chemotherapy in patients with relapsed [DLBCL], it improved outcomes, including survival.

[Polatuzumab] was approved a couple of years ago for patients with relapsed disease. Previously, [the agent] had also been studied [in combination] with R-CHOP except for 1 drug, vincristine, [which] was dropped because both [agents] cause peripheral neuropathy. We call that regimen pola-R-CHP, [which] was shown to be effective and safe in a trial of [patients with this disease]. However, we did not know whether [this regimen] was better than R-CHOP. To understand that you must conduct a randomized trial, and that is what POLARIX was.

What was the design of POLARIX and what were the key findings?

POLARIX was a randomized trial where patients with [newly diagnosed] DLBCL were randomly assigned to receive either R-CHOP or pola-R-CHP. All patients received 6 cycles of that treatment and then an extra 2 cycles of rituximab.

The pola-R-CHP regimen improved several of the end points of the trial, [including] PFS and event-free survival; it also reduced the need for additional therapies, such as second-line chemotherapy, radiation therapy, and stem cell transplant.

Those were all the beneficial effects, although [the regimen] did not improve overall survival [OS]. So far, we do not see an OS benefit [over R-CHOP]. The toxicity profile was comparable to that of R-CHOP. No tremendous differences in adverse effects [were observed] between the 2 [regimens].

What are the next steps with for the pola-R-CHP regimen?

We need to decide whether this [regimen] can, and should, be applied to patients across the country and around the world. That means [we need these data to be] reviewed by experts in the field and reviewed by regulatory authorities. The 2021 ASH Annual Meeting is the first [time that] we have heard about the data, [so it] needs to be published, reviewed, [and then better] understood by the community [before] decisions will be made [on whether the regimen] is the new standard. Also, is [the regimen] going to get paid for and covered? [Once we know] that, its [use] could potentially be applied in clinical practice across the globe.

Reference

1. Tilly H, Morschhauser F, Sehn LH, et al. The POLARIX study: polatuzumab vedotin with rituximab, cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy in patients with previously untreated diffuse large B-cell lymphoma. Blood. 2021;138(suppl 2):LBA-1. doi:10.1182/blood-2021-154729