Polatuzumab vedotin-piiq in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone resulted in a statistically significant and clinically meaningful improvement in progression-free survival vs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with diffuse large B-cell lymphoma.
Polatuzumab vedotin-piiq (Polivy) in combination with rituximab (Rituxan), cyclophosphamide, doxorubicin, and prednisone (R-CHP) resulted in a statistically significant and clinically meaningful improvement in progression-free survival (PFS) vs rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in previously untreated patients with diffuse large B-cell lymphoma (DLBCL), meeting the primary end point of the phase 3 POLARIX trial (NCT03274492).1
Moreover, the safety outcomes reported with the regimen proved to be consistent with what has previously been reported in other clinical trials.
The data from the trial are anticipated to be shared at an upcoming medical conference, according to Roche. Moreover, the findings will also be submitted to global health authorities as soon as possible.
“Since 40% of people with DLBCL relapse after initial therapy, achieving meaningful treatment effects in the frontline setting has the potential to be transformative,” Levi Garraway, MD, PhD, chief medical officer, and head of Global Product Development, at Roche, stated in a press release. “This [polatuzumab vedotin] regimen is the first in 2 decades to improve PFS in DLBCL compared with the standard of care, and we look forward to sharing these results with health authorities to bring this important potential new treatment option to patients as soon as possible.”
In the international, double-blind, placebo-controlled, phase 3 trial, investigators set out to examine the safety, efficacy, and pharmacokinetics of polatuzumab vedotin plus R-CHP compared with R-CHOP in the treatment of 879 patients with previously untreated DLBCL.
To be eligible for enrollment, patients needed to have archival or freshly collected tumor tissue available prior to study start, an International Prognostic index score ranging from 2 to 5, an ECOG performance status of 0 to 2, and a life expectancy of at least 1 year.2 Moreover, patients needed to have a left ventricular ejection fraction of at least 50%, and acceptable hematologic function.
If patients had a history of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies, a contraindication to any of the individual components of CHOP, or they previously underwent organ transplant, they were excluded. Other exclusion criteria included those with greater than grade 1 peripheral neuropathy, a demyelinating form of Charot-Marie-Tooth disease, a history of indolent lymphoma or grade 3B follicular lymphoma, primary mediastinal large B-cell lymphoma, Burkitt lymphoma, or those who previously received cytotoxic drugs within 5 years of screening for any condition.
Study participants were randomized 1:1 to receive either polatuzumab vedotin plus R-CHP plus a vincristine placebo for the duration of 6 treatment cycles, followed by rituximab for 2 cycles; or R-CHOP plus a polatuzumab vedotin placebo for 6 cycles, followed by 2 cycles of rituximab.
The primary end point of the trial was PFS per investigator assessment, utilizing the Lugano Response Criteria for malignant lymphoma.
Previously, in June 2019, the FDA granted an accelerated approval to polatuzumab vedotin for use in combination with bendamustine and rituximab (BR) for the treatment of patients with relapsed/refractory DLBCL who have previously received at least 2 therapies.3
The regulatory decision was based on data from the phase 1b/2 GOG29365 trial (NCT02257567), which demonstrated that 40% (95% CI, 25%-57%) of patients who received the regimen containing the antibody-drug conjugate experienced a complete response (CR) to treatment, meeting the primary end point of the trial; only 18% (95% CI, 7%-33%) of patients responded to treatment in the BR-alone arm (P = .026).
Updated data from the trial indicated that at a median follow-up of 42.9 months in the randomized arm (n = 40), the median independent review committee (IRC)–assessed PFS was 9.2 months (95% CI, 6.0-13.0) in the investigative arm vs 3.7 months (95% CI, 2.1-4.5) in the control arm (HR, 0.40; 95% CI, 0.2-0.7).4 In the ADC-containing arm, 15% of patients (n = 6) had an IRC-assessed duration of response of longer than 24 months (range, 26.6-38.6) at the last follow-up.
In the extension cohort (n = 106), the best overall response rate was 56.6% and the best CR rate was 52.8%. The median IRC-assessed PFS and OS in this group were 6.1 months (95% CI, 5.1-8.0) and 11.0 months (95% CI, 8.3-14.2), respectively. OS data, however, were not fully mature.
Regarding safety, no new signals were reported with polatuzumab vedotin plus BR. A safety analysis among all patients who received the ADC-containing regimen in the safety run-in, randomized, and extension cohorts (n = 151), 80.1% experienced grade 3 or 4 toxicities and 55.6% had serious adverse effects (AEs). Moreover, 11.9% of patients experienced grade 5 AEs, which were primarily infections.
In February 2020, the United Kingdom’s National Institute for Health and Care Excellence chose not to recommend the combination of polatuzumab vedotin and BR for use in adult patients with relapsed/refractory DLBCL who are unable to undergo hematopoietic stem transplant.5
Although evidence suggests that patients who receive the ADC-containing regimen experience prolonged PFS and overall survival vs those who receive BR alone, the final findings from the phase 1b/2 GOG29365 trial were not yet available and the cost-effectiveness estimates for the regimen remain uncertain because of limitations in available data and methods used.