NICE Recommends Frontline Brentuximab Vedotin Combo for Systemic Anaplastic Large Cell Lymphoma

The United Kingdom’s National Institute for Health and Care Excellence (NICE) has recommended brentuximab vedotin (Adcetris) in combination with cyclophosphamide, doxorubicin, and prednisone (CHP) as a treatment option in treatment-naïve patients with systemic anaplastic large cell lymphoma (sALCL).¹

“Being diagnosed with a rare type of lymphoma, like sALCL, can have a significant impact on the quality of life of patients and their family or friends. Not only can the disease and the current treatment options have a physical impact, but the psychological impact of being diagnosed with a rare cancer, with potentially poor outcomes, can be devastating,” Stephen Scowcroft, director of Operations and External Affairs of Lymphoma Action, commented in a press release.² “That is why we are really pleased that newly diagnosed patients can now have access to an effective treatment that can improv their quality of life and outcomes.”

The recommendation, which reflects the marketing authorization extension from the European Commission, is based on data from the pivotal phase 3 ECHELON-2 trial, in which the brentuximab vedotin combination led to a 29% reduction in the risk of disease progression or death (hazard ratio [HR], 0.71; 95% CI, 0.54-0.93; P = .011) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in patients with CD30-positive peripheral T-cell lymphoma, including the sALCL subtype.³ The median PFS was 48.2 months in the brentuximab regimen arm (95% CI, 35.2–not evaluable) versus 20.8 months (95% CI, 12.7-47.6) in the CHOP arm.⁴

In the double-blind, multicenter, placebo-controlled trial, approximately 452 newly diagnosed patients with CD30-expressing PTCL were enrolled and 226 were randomized to receive brentuximab vedotin plus CHP or standard CHOP for 6 or 8 1-day treatment cycles. Randomization was stratified by histological subtype per local pathology assessment and by international prognostic index score.

All patients were given 750 mg/m2 of cyclophosphamide and 50 mg/m2 of doxorubicin intravenously on day 1 of each cycle and 100 mg of oral prednisone once daily on days 1 to 5 of each cycle, followed by either 1.8 mg/kg of brentuximab vedotin and a placebo form of vincristine intravenously or 1.4 mg/m2 of vincristine and a placebo form of brentuximab vedotin intravenously on day 1 of each cycle.

The primary end point of the trial was PFS per independent review, and secondary end points included OS, PFS in patients with sALCL, ORR, CR rate, and safety.

Additional results showed that the brentuximab vedotin regimen also resulted in an improvement in overall survival (OS; HR, 0.66; 95% CI, 0.46-0.95; P = .024). The combination also showed superiority over standard CHOP with regard to objective response rate (ORR; 83% vs 72%; P = .003), complete remission rate (CR; 68% vs 56%; P = .007), and progression-free survival (PFS) in the sALCL subgroup (HR, 0.59; 95% CI, 0.42-0.84; P =.003). The HR for OS in this subgroup of patients was 0.54 (P = .0096); this translated to a 46% reduction in the risk of death with the combination.

With regard to safety, the adverse events (AEs) reported proved to be similar between the treatment arms. These events included febrile neutropenia (18% in the brentuximab arm vs 15% in the CHOP arm) and peripheral neuropathy (52% vs 55%, respectively). Fatal AEs occurred in 3% of patients who received the brentuximab combination versus 4% of those who received CHOP.

In the final appraisal document, the committee acknowledged the need for a better therapeutic option for treatment-naïve patients with sALCL. The most plausible incremental cost-effectiveness ratio for brentuximab vedotin in combination with CHP compared with CHOP was £23,446 per quality-adjusted life year gained. As such, the committee concluded that the combination could be considered as a cost-effective use of National Health Service (NHS) resources, and thus, they recommended the regimen as an option for this patient population.

“Brentuximab vedotin is a medicine that continues to innovate and transform the treatment paradigm for patients with rare types of lymphoma. We are committed to working in partnership with the clinical and patient community, and NICE and NHS England, to ensure as many eligible patients can benefit from access to this medicine as possible,” Joe Neal, managing director of Takeda UK & Ireland, stated in the press release. “We are therefore delighted that NICE recognized the significant benefit that brentuximab can bring to patients with this aggressive disease and we hope this rapidly becomes the new standard of care.”

Brentuximab vedotin is already available as a monotherapy for use in adult patients with relapsed/refractory sALCL in England, Wales, and Northern Ireland, following progression on at least 1 chemotherapy agent. In May 2020, the European Commission approved the combination for use as a frontline treatment in adult patients with sALCL.

The agent is also approved in Europe for the treatment of adult patients with previously untreated CD30-positive stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine; adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following autologous stem cell transplant (ASCT); adult patients with relapsed/refractory CD30-positive Hodgkin lymphoma following ASCT or following at least 2 prior therapies when ASCT or multiagent chemotherapy is not an option; and adult patients with CD30-positive cutaneous T-cell lymphoma after at least 1 prior systemic therapy.

References

1. Final appraisal document: Brentuximab vedotin in combination for untreated systemic anaplastic large cell lymphoma. National Institute for Health and Care Excellence. June 2020. Accessed July 9, 2020. bit.ly/2AIMLjC.
2. NICE recommends Adcetris (brentuximab vedotin), in combination with chemotherapy, as frontline treatment for a rare type of lymphoma. News release. Takeda UK Ltd. July 9, 2020. Accessed July 9, 2020.
3. FDA grants breakthrough therapy designation to Adcetris (brentuximab vedotin) for frontline peripheral T-cell lymphomas. News release. Seattle Genetics. November 15, 2018. Accessed July 9, 2020. bit.ly/3iOLclB.
4. Horwitz S, O’Connor OA, Pro B, et al. Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial. Lancet. 2019;393(10168):229-240. doi:10.1016/S0140-6736(18)32984-2