Researchers reviewing real world data from the first 400 patients with large B cell lymphoma treated with CAR-T in the UK have reported similar efficacy to the clinical trials and a lower rate of significant toxicities.
But the researchers stressed that in this first dataset providing full intention to treat outcomes from a national cohort of eligible patients, a substantial 26% failed to proceed to CAR-T therapy.
Overall, in this first two years of the national roll out of CAR-T in B cell lymphoma in the UK, 292 patients received axicabtagene ciloleucel (axi-cel) and 112 tisagenlec-leucel (tisa-cel).
Among the 300 patients who were infused, there was a 42% 12-month progression free survival for axi-cel and 27% for tisa-cel, researchers reported in the British Journal of Haematology.
Patients who had a complete remission at six months had around a 90% chance of ongoing remission at 18 months after CAR-T infusion, the analysis showed.
But 52% of responding patients had only a transient response and progressed by month six.
Between December 2018 and November 2020 – the period captured by the study – there was an improvement in outcomes which reflects the learning curve of teams implementing this new and complex treatment, the researchers said.
Looking at factors which might predict outcome, the team noted that two or more high risk factors (including high LDH) was associated with a more than five-fold increased risk of primary failure compared to no risk factors.
However, they noted that risk factors that were identified are known prognostic factors in this group of patients and not specific to CAR-T, making it difficult to draw conclusions for daily practice.
The study also said the two CAR-T products could not be directly compared but Tisa-cel was less commonly used in patients with bulky disease and more commonly used in elderly patients, which reflected its more favourable toxicity profile.
A low rate of severe toxicities was in line with greater use of tocilizumab and corticosteroids in daily practice, than seen in clinical trials, the researchers added.
Study leader Dr Andrea Kuhnl, consultant haematologist at King’s College Hospital NHS Foundation Trust, said the UK was in a unique position to analyse data from a cohort selected by uniform, centrally reviewed criteria because of the setting up of a national panel to determine patient eligibility.
“There is always a selection bias in trials where you pick the younger fitter patients,” she said speaking with the limbic. “So you still need to provide evidence from a real world setting.”
“It’s interesting for us to analyse data from the UK because we have this unique system of centralised approval. We have a full intention to treat cohort which is really informative because a significant number of patients dropped out.”
The findings are reassuring, she said, and would feed into NICE’s decision making on the treatments which are currently being made available through the Cancer Drugs Fund.
“The patients who went on to have CAR-T, the outcomes are very similar to the clinical trials. The safety profile was more favourable for both products with relatively low rates of significant toxicity. That has been better in the real world setting particularly with axi-cel and neurotoxicity.”