The background of our study has been to do an adjusted comparison of the CARTITUDE-1 outcomes versus real world clinical practice observed from the prospective LocoMMotion study. Cilta-cel is a BCMA CAR T evaluated in the CARTITUDE-1 clinical study. This study showed how cilta-cel was very effective in relapsed and refractory myeloma patients triple drug class exposed and, basically, the majority of the patients were triple drug class refractory. But these patients were just a single arm study and this means that there was not any standard of care in order to compare the results of the CARTITUDE-1 clinical study. This was the rationale why the LocoMMotion study was conducted and the LocoMMotion has been the first prospective observational study based on the evaluation of the different regimes utilised in real life for the rescue of the triple drug class refractory myeloma patients. So this means that the LocoMMotion study both represents the comparator arm for the CARTITUDE-1 clinical study in which cilta-cel was evaluated. Basically, this was the rationale for this comparison and, indeed, the key baseline characteristics of the patients included in both clinical studies were quite comparable. In principle, myeloma patients that had received at least three prior therapies or were double refractory to immunomodulatory drugs and proteasome inhibitors and had received an IMiD, PI and anti-CD38 monoclonal antibodies were the key eligibility criteria in both studies. This was the main reason why the comparison is possible.

The first important finding is to remark that CARTITUDE-1 evaluated clita-cel single agent and in the LocoMMotion study when the rescue therapies were evaluated in the triple drug class refractory myeloma patients it is important to note that 92 unique regimens were used as rescue therapy in the real world setting. This means that there is not any standard of care for these patients triple drug class refractory. When the comparison was done from the efficacy point of view, in terms of overall response rate patients treated with clita-cel were three times as likely to achieve a response and more than five times as likely to have a better than very good partial response than those treated with conventional therapies. But most remarkable, 83% of the patients treated with cilta-cel achieved at least a complete response compared with just one patient in the LocoMMotion that achieved complete response.

Following with the overall response rate when the progression free survival, as well as the overall survival, was evaluated, a significant benefit has been reported for cilta-cel versus the LocoMMotion study. When cilta-cel was evaluated and was utilised in relapsed and refractory myeloma patients the probability of reduction of progression noted was by 85% in comparison with the population included in the LocoMMotion. In terms of overall survival the risk of death was reduced by 80% in the cilta-cel in comparison with the LocoMMotion. So this means that definitely there is a clear benefit in terms of efficacy for cilta-cel versus standard of care in the real world setting evaluated in the LocoMMotion study.

But also I would like to remark on the fact that the quality of life was also evaluated because of the prospective nature of the LocoMMotion study. When this comparison was done, overall the quality of life was also significantly better for cilta-cel versus the LocoMMotion study.

This study showed clearly how patients treated with cilta-cel in the CARTITUDE-1 achieved the highest overall response rate, complete response rate and the longest progression free survival seen in this patient population, patients basically triple drug class refractory. In direct comparison with the population included in the LocoMMotion demonstrated that cilta-cel provides a clinically and statistically significant improvement in outcomes, including response, PFS, overall survival but also quality of life. Definitely all these data provide the highest qualitative real world comparative evidence for cilta-cel and highlights its potential as a highly effective treatment option for patients with triple class exposed relapse and refractory multiple myeloma.

Definitely this type of comparison is appropriate because of the innovative nature of the BCMA CAR T therapy like cilta-cel. This type of comparison is necessary because we had the opportunity to see how in the LocoMMotion there is not any standard of care for this population. So cilta-cel in this case, BCMA CAR T, is going to cover the unmet medical need we have in these triple drug class refractory myeloma patients.