Keytruda (pembrolizumab) is suggested as an alternative for managing recurring or stubborn classical Hodgkin lymphoma in individuals aged 3 years and above who have undergone at least 2 prior treatments and are ineligible for an autologous stem cell transplant (ASCT).
It's advised under these conditions:
They have previously undergone brentuximab vedotin.
Pembrolizumab treatment is discontinued after a span of 2 years or earlier if the individual undergoes a stem cell transplant or if the disease progresses
KEYNOTE‑087, an ongoing single-arm, open-label examination of pembrolizumab, involves 81 participants with recurrent or resistant classical Hodgkin lymphoma post salvage chemotherapy and brentuximab vedotin but without ASCT. The corporation provided evidence from the 5-year data-cut (March 2021) of KEYNOTE‑087.
The committee evaluated that the overall response rate to pembrolizumab was 64% according to a blinded, independent central review (primary measure).
Out of a median follow-up period of 62 months, 24 individuals (30%) passed away. At the 12-month mark, 96% of pembrolizumab recipients were still alive, at 24 months, the survival rate was 91%, and at 48 months, it stood at 77%. The committee pointed out that the survival data from the trial was not fully developed. Additionally, it observed that 30% of the participants underwent a stem cell transplant (autologous or allogenic) following pembrolizumab treatment. The median interval to a stem cell transplant was 30 months.
Real-world data regarding the utilization of pembrolizumab during managed access originated from the Systemic Anti-Cancer Therapy (SACT) registry. Observational data from the SACT dataset for 215 individuals who received pembrolizumab through the Cancer Drugs Fund was provided by Public Health England.
The median follow-up period was 19 months. The median duration of pembrolizumab treatment was 5 months, and the median overall survival was yet to be determined. At the end of 12 months, 82% of pembrolizumab recipients were still alive, at 24 months, the rate dropped to 68%, and at 48 months, it further decreased to 55%.
The committee remarked that the overall survival rates were inferior in SACT compared to the KEYNOTE‑087 study.
The model structure presented by the company comprised 4 distinct health states with a significant transition point (referred to as a landmark) at 4 years. Prior to the landmark, the health states were 'alive pre-landmark' and 'death'. Post-landmark, individuals were categorized by stem cell transplant status based on the likelihood of undergoing the procedure. The health states included 'alive post-landmark with no or a failed stem cell transplant', 'alive post-landmark with a successful stem cell transplant', and 'death'. The model's time horizon was 40 years, and there was no application of treatment-effect attenuation. The company asserted that its structure reflected the potential of pembrolizumab as a transitional measure to a stem cell transplant, which could potentially lead to a cure. Moreover, it highlighted that the model structure allowed for the possibility of individuals undergoing another cycle of chemotherapy after pembrolizumab treatment. The company rationalized that the landmark point was set at 4 years to encompass all stem cell transplant-related occurrences.
NICE's handbook on health technology assessment specifies that beyond a most plausible ICER of £20,000 per QALY gained, deliberations concerning the suitability of a technology as an efficient utilization of NHS resources will consider the level of certainty surrounding the ICER.
The committee will exercise greater caution in recommending a technology if there's less certainty surrounding the presented ICERs. The committee acknowledged that there existed some uncertainty in the modeling of pembrolizumab compared to standard care.