Pembrolizumab for Treating Relapsed or Refractory Classical Hodgkin Lymphoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

Abstract

As part of its Single Technology Appraisal (STA) process, the National Institute for Health and Care Excellence (NICE) invited the manufacturer (Merck Sharp & Dohme; MSD) of pembrolizumab (Keytruda ® ) to submit evidence of its clinical and cost effectiveness for the treatment of patients with relapsed or refractory classical Hodgkin lymphoma (RRcHL) who did not respond to treatment with brentuximab vedotin. Kleijnen Systematic Reviews Ltd, in collaboration with Maastricht University Medical Centre+, was commissioned to act as the independent Evidence Review Group (ERG). The ERG produced a detailed review of the evidence for the clinical and cost effectiveness of the technology, based on the company’s submission to NICE. According to the NICE scope, pembrolizumab was compared with single or combination chemotherapy. Comparisons were undertaken in two populations: patients who did and did not receive prior autologous stem cell transplant (autoSCT; populations 1 and 2, respectively). Despite it having been recommended by NICE in population 1 at the time the ERG received the company submission, nivolumab was not included as a comparator. No studies directly comparing pembrolizumab and its comparators were identified. One ongoing, single-arm study of the efficacy and safety of pembrolizumab (KEYNOTE-087) and one comparative observational study (Cheah et al., 2016) were used to inform the comparative effectiveness of pembrolizumab and standard of care (SoC), using indirect comparisons in both populations. Almost all analyses showed significant PFS and overall response rate benefits for pembrolizumab versus SoC, but due to being based on indirect comparison, were likely to contain systematic error. The economic evaluation therefore suffered from substantial uncertainty in any estimates of cost effectiveness. Furthermore, there was a lack of evidence on the uptake and timing of allogeneic stem cell transplant, and alternative assumptions had a significant impact on cost effectiveness. Immature survival data from KEYNOTE-087 exacerbated this issue and necessitated the use of alternative data sources for longer-term extrapolation of survival. Some issues identified in the company’s analyses were amended by the ERG. The revised ERG deterministic base-case incremental cost-effectiveness ratios based on the company’s second Appraisal Consultation Document response for pembrolizumab versus SoC (with a commercial access agreement) for populations 1 and 2 were £54,325 and £62,527 per quality-adjusted life-year gained, respectively. There was substantial uncertainty around these ICERs, especially in population 2. NICE did not recommend pembrolizumab as an option for treating RRcHL in population 1, but recommended pembrolizumab for use within the Cancer Drugs Fund in population 2.

Recurrent COVID-19 Infection in a Refractory/Classical Hodgkin's Lymphoma Patient Undergoing Autologous Stem Cell Transplantation: A Case Report

“…The patient presented here has failed the first-line treatment of antibody-drug conjugate therapy as well as the salvage therapy since new legions have developed, as shown in the PET scan. It has been demonstrated that unresponsive adult patients to at least one line of chemotherapy and/or salvage therapy are candidates for pembrolizumab (a PD-1 inhibitor) preceding ASCT [30]. Therefore, in line with the previous study, the patient in this report was started on immune-engage therapy (pembrolizumab), which successfully resolved the previous pelvis and abdominal lymph nodes.…”

Lenalidomide with Rituximab for Previously Treated Follicular Lymphoma and Marginal Zone Lymphoma: An Evidence Review Group Perspective of a NICE Single Technology Appraisal

“…On the other hand, there may be comparators that only become relevant after the final scope has been issued. As highlighted by Grimm et al [ 22 ], it is important to also include the possibility of addition of comparators under appraisal at the time.…”

Monoclonal antibodies used for management of hematological disorders

“…[38] However, in relapse/refractory Hodgkin's disease it was found similarly useful as Nivolumab and has been approved by FDA for the use. [39] This drug has been associated with various hematological disorders like TTP (Thrombotic Thrombocytopenic Purpura) and autoimmune hemolytic anemia.…”