The European Commission has granted a conditional marketing authorization to polatuzumab vedotin in combination with bendamustine and rituximab for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma who are ineligible for hematopoietic stem cell transplant.
Levi Garraway, MD, PhD
The European Commission has granted a conditional marketing authorization to polatuzumab vedotin (Polivy) in combination with bendamustine and rituximab (Rituxan; BR) for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who are ineligible for hematopoietic stem cell transplant.1
The conditional approval is based on findings from the phase Ib/II GO29365 study, in which the polatuzumab vedotin regimen demonstrated an improvement in response rates and overall survival (OS) compared with BR in patients with relapsed/refractory DLBCL who are not candidates for hematopoietic stem cell transplant. The complete response (CR) rate with polatuzumab vedotin was 40% compared with 17.5% with chemotherapy alone (P = .026), as determined by an independent review committee (IRC).
Additionally, the median OS in patients who received polatuzumab vedotin with BR was 12.4 months compared with 4.7 months for patients who received BR alone (HR, 0.42; 95% CI, 0.24-0.75; P = .002). The investigator-assessed median duration of response (DOR) was 10.3 months and 4.1 months for polatuzumab vedotin/BR and BR alone, respectively (HR, 0.44).
“With this approval, people in the EU with relapsed or refractory diffuse large B-cell lymphoma will have the opportunity to benefit from this new Polivy combination,” Levi Garraway, MD, PhD, chief medical officer and head of global product development, Roche, the developer of polatuzumab vedotin, stated in a press release. “For patients battling this aggressive disease, the prognosis is poor and few treatments are available. We are proud to bring this first-in-class treatment option to those who need it most.”
The approval follows a November 2019 decision by the European Medicines Agency’s Committee for Medicinal Products for Human Use to recommend the approval of the antibody-drug conjugate in combination with BR as a treatment for patients with DLBCL in this setting.
Preliminary results from the phase Ib part of the GO29365 trial were reported prior to the 2018 ASH Annual Meeting. At the meeting, the data that were presented included 6 patients treated with polatuzumab vedotin/BR from the safety cohort, 27 from the expansion phase, and 80 from the randomized comparison of BR with or without polatuzumab vedotin.2
The median age across the cohorts ranged from 65 to 71, and from two-thirds to three-fourths of the patients in each cohort had received ≥2 prior lines of therapy. Additionally, 15% of the patients in the randomized study had undergone transplant.
The primary endpoint of CR was determined by independent review of PET—CT imaging at the end of treatment; secondary endpoints included DOR and progression-free survival (PFS) by independent review. Exploratory endpoints included DOR and PFS by investigator review, OS, and efficacy by cell of origin and MYC/BCL2 double-expression (DE) status.
The median follow-up was 37.6 months for the safety cohort, 27.0 months for the expansion cohort, and 22.3 months for the randomized comparison. Three of 6 patients in the safety cohort achieved CR with the polatuzumab vedotin regimen; DOR, PFS, and OS could not be determined.
In the expansion cohort, updated data showed that the end of treatment (EOT) IRC-assessed CR rate was 29.6%.3 Additionally, the median PFS and OS were 6.3 months and 10.8 months, respectively.
In the randomized, phase II component, the CR rate was 40% (n = 16) in the polatuzumab vedotin arm compared with 18% (n = 7) of patients who received BR alone. Moreover, the median PFS by IRC was 9.5 months with polatuzumab vedotin and 3.7 months without (HR, 0.36; 95% CI, 0.21-0.63; P <.001). By investigator assessment, the median values were 7.6 versus 2.0 months without (HR, 0.34; 95% CI, 0.20-0.57; P <.0001).
Analyses by cell of origin—activated B-cell like (ABC) or germinal B-cell like (GCB)—showed consistent advantages for the addition of polatuzumab vedotin. Median PFS by investigator assessment and OS in the ABC subgroup were 10.76 months and 15.38 months, respectively, versus 1.97 and 4.73 months without polatuzumab vedotin. The GBC subgroup had inferior outcomes yet still favored polatuzumab vedotin; the median PFS was 2.50 months versus 1.87 months and the median OS was 7.23 months versus 3.81 months.
An analysis by DE status showed that the median PFS was 7.03 months versus 1.40 months for those who received the polatuzumab vedotin regimen or BR alone among patients with DE and 6.16 versus 3.06 months for those without DE. The median OS was 8.90 with polatuzumab vedotin/BR versus 4.60 months with BR alone for the DE subgroup and 9.95 versus 4.53 months for patients without DE.
Regarding safety, Roche stated that the most commonly reported adverse events (AEs) in patients who received the polatuzumab vedotin regimen included anemia, thrombocytopenia, neutropenia, fatigue, diarrhea, nausea, and pyrexia.
Roche stated that a conditional approval is granted to a medicinal product that fulfills an unmet medical need where the benefit of immediate availability outweighs the risk of less comprehensive data than normally required.
In June 2019, the FDA granted an accelerated approval to polatuzumab vedotin in combination with BR for the treatment of patients with relapsed/refractory DLBCL who have received ≥2 prior therapies. Additional submissions of the GO29365 findings to health authorities worldwide are ongoing.