The survival of 51% of patients with relapsed / refractory multiple myeloma, who have already received at least three previous treatments, is prolonged by more than two years. To make this possible is cell therapy with a new Car T, ide-cel, thanks to which the median overall survival has exceeded two years (24.8 months). These are very important results considering that for these heavily pretreated patients, before the arrival of Car T, the median life expectancy was between 6 and 9 months. The results on prolongation of survival are related to the update of the KarMMa phase 2 study, which enrolled 128 patients treated with ide-cel and which were presented at the Congress of the European Hematology Association (EHA), which took place recently.
The effects on heavily pre-treated patients
Every year, in Italy, 5,800 people are affected by multiple myeloma, a blood cancer that originates in the bone marrow characterized by repeated relapses. Therefore, patients need more therapeutic options in the different phases of the disease, with the aim of making it chronic even in the most severe cases. “KarMMa is the first phase 2 study with CAR T cells designed and conducted for the therapy of relapsed / refractory multiple myeloma – says Michele Cavo, director of the Institute of Hematology ‘LA Seràgnoli’, Irccs S. Orsola-Malpighi, University of Bologna and full professor of Hematology at the same University. Enrolled patients had already received a median of 6 previous treatment regimens and 84% were refractory to all three commonly used classes of new drugs, which include immunomodulating agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies. “.
Survival data
The median duration of follow-up was 24.8 months, the longest so far achieved with CAR T therapy in multiple myeloma. The overall response rate reached 73% in all treated patients, with 33% of patients achieving a complete response. “The median duration of response – continues Cavo – was 10.9 months and the median progression-free survival was 8.6 months in the entire patient population. These results were confirmed in all subgroups of patients under study, in particular those at high risk (extramedullary disease, high cytogenetic risk, etc.) “.
The innovation of the Car T.
Car T cell therapy, based on the patient’s genetically modified lymphocytes, represents the most advanced front of immunotherapy. The T lymphocytes are taken from the patient, engineered in the laboratory with a complex procedure and then reinfused into the patient. The ‘Seràgnoli’ Institute of Hematology of Bologna actively participated in the KarMMa study, which showed results up to 5 times higher than those currently estimated for this patient population, who no longer respond to any available therapy and with an expectation of limited life. Furthermore, thanks to the high tolerability demonstrated also by a separate neurotoxicity analysis, CAR T therapy guarantees a good quality of life. The study confirms the efficacy of ide-cel in potential long-term disease control.
The chronicity of the disease
If Car T therapy represents the last frontier of scientific research, the therapeutic innovation in the last 20 years has been constituted by the introduction of drugs with direct action towards plasma cells and the ‘medullary microenvironment’, first of all immunomodulators. Thanks to these weapons the goal of the chronicization of the disease is increasingly a reality for some patients. In fact, in twenty years the median survival has gone from about 36 months to 7 years.
The effectiveness of the ‘triplet’
At the EHA Congress, a study on the combination of three different drugs was also presented in an oral session: the study evaluates the efficacy and safety of different therapeutic combinations in specific groups of patients, the first triplet analyzed is constituted by iberdomide, dexamethasone ( cortisone) and daratumumab (monoclonal antibody), the second from iberdomide, dexamethasone and bortezomib (proteasome inhibitor) and the third from iberdomide, dexamethasone and carfilzomib (proteasome inhibitor). “Iberdomide is a potent Cereblon modulator, a component of a protein complex that is the target of the immunomodulators lenalidomide and pomalidomide, compared to which it is much more potent. In this study – concludes Cavo – heavily pretreated patients were enrolled, with at least 4 previous therapy regimens. The phase II recommended dose has been defined for the combination iberdomide, dexamethasone and daratumumab (1.6 mg). The identification of the dosage is a further step in the development process of iberdomide, which brings it closer to use in practice. Furthermore, the good tolerability of the three triplets based on iberdomide emerged. The efficacy profile is also relevant, with an overall response probability of 41% for the combination with daratumumab and almost 60% with the proteasome inhibitors ”.
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