The United Kingdom’s National Institute for Health and Care Excellence has chosen not to recommend polatuzumab vedotin plus rituximab and bendamustine for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma who cannot undergo hematopoietic stem cell transplant.
The United Kingdom’s National Institute for Health and Care Excellence (NICE) has chosen not to recommend the combination of polatuzumab vedotin (Polivy) with rituximab (Rituxan) and bendamustine (BR) for use in adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who cannot undergo hematopoietic stem cell transplant.1
Although clinical evidence suggests that patients who receive the combination experience prolonged progression-free and overall survival compared with those who receive BR alone, final data from the phase Ib/II GOG29365 trial (NCT02257567) examining the use of the triplet are not yet available, the agency stated in the appraisal consultation document.
Moreover, the cost-effectiveness estimates for the polatuzumab vedotin combination remain uncertain due to limitations in the data available and methods used, NICE added.
“It is considered a life-extending treatment at the end of life, but the cost-effectiveness estimates are too uncertain,” the committee wrote. “Therefore, it cannot be recommended for routine use in the National Health Service or for use in the Cancer Drugs Fund.”
The recommended dose of polatuzumab vedotin is 1.8 mg/kg, to be administered intravenously every 21 days in combination with BR for 6 cycles, according to the agency. When given with polatuzumab vedotin, the recommended dose of bendamustine is 90 mg/m2 daily on days 1 and 2 of each cycle; the recommended dose of rituximab is 375 mg/m2 on day 1 of each cycle. Polatuzumab vedotin should not exceed a dose of 240 mg per cycle.
The cost per item is £11,060 per 140-mg vial, excluding value added tax. As such, the average cost of a course of treatment is estimated to be £50,416.
In June 2019, the FDA granted an accelerated approval to polatuzumab vedotin for use in combination with BR in the treatment of patients with relapsed/refractory DLBCL who have received ≥2 prior therapies. The approval of the antibody-drug conjugate was based on data from the multicenter, randomized, open-label GO29365 trial, which showed that 40% of patients who received the triplet achieved a complete response (CR) compared with 18% of patients who received BR alone (P = .036).2
The overall response rate was 63% with the triplet versus 25% with the doublet. Of 25 patients who achieved a partial response (PR) or CR to the polatuzumab vedotin regimen, 64% (n = 16) experienced a duration of response (DOR) of ≥6 months; 48% (n = 12) had a DOR of ≥12 months.
Preliminary findings from the phase Ib portion of the trial provided evidence supporting the safety and efficacy of polatuzumab vedotin in the safety run-in, expansion, and randomized cohorts. At the 2018 ASH Annual Meeting, data were presented on 6 patients from the safety cohort, 27 from the expansion phase, and 80 from the randomized comparison portion of the trial.
Results showed that half of the patients (n = 3) in the safety cohort achieved a CR with the triplet. DOR, progression-free survival (PFS), and OS could not be determined at the time. Forty-one percent (n = 11) of patients in the expansion cohort experienced objective responses via independent review. The median DOR with the polatuzumab vedotin regimen was 28.4 months, while the median PFS and OS were 5.4 months and 10.8 months, respectively.
Updated data from the randomized, phase II portion of the trial showed that patients who received the polatuzumab vedotin regimen experienced a significantly higher independent review committee (IRC)—assessed CR of 40.0% versus 17.5% in those who were given the BR regimen (P = .026). Additionally, treatment with the triplet resulted in a superior median PFS compared with the doublet, at 9.5 months versus 3.7 months (HR, 0.36; 95% CI, 0.21-0.63; P <.001). The polatuzumab vedotin regimen reduced the risk of death by 58% compared with BR alone (HR, 0.42; 95% CI, 0.24-0.75; P =.002).3
With regard to safety, those who received the polatuzumab vedotin regimen experienced higher rates of grade 3/4 neutropenia (46.2% vs 33.3%), anemia (28.2% vs 17.9%), and thrombocytopenia (41.0 % versus 23.1%) compared with BR alone. Similar rates of grade 3/4 infections were reported between the triplet and doublet arms, at 23.1% versus 20.5%, respectively.
“The committee concluded that polatuzumab vedotin is a promising new treatment and that evidence from the trial to date suggests that it extends both PFS and OS,” the agency stated.
No standard treatment exists for patients with relapsed/refractory DLBCL who are unable to undergo a hematopoietic stem cell transplant; these patients are only able to receive BR, and this regimen is not a standard of care in the National Health Service. According to the agency, there is a high unmet need for effective treatments in patients with relapsed/refractory disease, who are known to have an extremely poor prognosis with a median survival of under 1 year.
“Clinical trial evidence shows that polatuzumab vedotin with BR increases PFS and OS compared with BR alone. However, there is substantial uncertainty in the modelling and the committee was not persuaded that polatuzumab vedotin has been shown to be cost effective,” the committee concluded. “Therefore, polatuzumab vedotin with BR is not recommended for relapsed or refractory DLBCL in adults who cannot have a hematopoietic stem cell transplant.”