“Bring the army as close as possible to the enemy”. Or: “Attack the enemy on two fronts at the same time”. Thus, using war metaphors – as usual in the narration of oncology – the researchers responsible for two different clinical trials just presented at the annual congress of the American Society of Hematology (ASH) have defined the action of a particular class of immunotherapeutic anticancer drugs , the so-called bispecific antibodies: molecules more powerful than conventional ones and capable of targeting diseased cells more effectively, to stop the progression of cancer and minimize the risk of recurrence. Both treatments being tested – one of which was tested (also) in Italy, by a team of the Romagna Scientific Institute for the study and treatment of tumors (Irst) Irccs of Meldola coordinated by Claudio Cerchione – act against myeloma, a very aggressive blood cancer that develops from blood cells found in the bone marrow. The principle of action is the same, and is well described by the adjective “bispecific”: the molecule acts in two ways, on the one hand by binding to the T cells (the cells of the immune system responsible for eliminating pathogens) and on the other to tumor cells. As if it brought, precisely, the killer close to the victim, or vice versa.
Let’s see them one at a time. The first treatment is Phase 1 trials of a bispecific antibody, called alnuctamab, for the most severe, refractory and relapsing cases of multiple myeloma. And it involved patients for whom no conventional treatment was no longer available, i.e. patients on whom all other available therapies had already been tried without positive results. “This bispecific antibody”, explained Cerchione, who presented the study at the ASH congress, “represents a unique therapeutic opportunity for patients who have exhausted all conventional treatments, and for whom all that was left was palliative care ”. The clinical trial was conducted in double blind on 40 patients and its efficacy was evaluated compared to placebo (since, as already mentioned, there were no therapeutic alternatives). The results are very satisfactory: “Being a phase 1 clinical trial”, continues Cerchione, “the first objective was to establish the dosage of the drug and to evaluate its safety. And indeed we have found that the drug is safe, very well tolerable, non-toxic, quick and easy to administer – the administration is subcutaneous, which has an excellent impact on patient compliance”.
But the study also made it possible to discover something about the drug’s efficacy: “We obtained a total positive response in 77% of patients, and for 50% of them this response was of high quality, i.e. a significant and detectable improvement both at level of disease reduction and quality of life of patients”. These results make clinicians very confident for the future: “Our way of treating this type of tumor has changed a lot”, continues the expert. “Ten years ago, the patients in my practice looked very different than they do today: they are much better today. We are becoming increasingly capable of treating myelomas: however, it is also important to insist on strengthening maintenance therapies, those which, after treatment, help keep the tumor under control, making it chronic and avoiding recurrences. The final goal, the most ambitious, is to arrive in even more cases at the so-called Mrd-negativity [Mrd sta per minimal residual disease, ovvero residuo minimo di malattia, nda], i.e. a stage in which cancer cells are no longer detectable by the tools we have at our disposal. And at treatment-free remission, the moment in which the patient is equal to the general population and no longer needs to take any medication. When we get there we will be able to say that we have really cured cancer ”.
The second treatment is called talquetamab, and had already successfully passed the phase 1 clinical trial, which was conducted between January 2018 and November 2021 and which had established its safety and established the dosage, as described in a published article in the New England Journal of Medicine. The results presented above relate to the subsequent clinical trial, conducted on 143 patients who received a weekly dose of the treatment and 145 patients who received a higher dose, twice a week. All the patients involved had already received at least three other different therapies and had never achieved complete remission of the disease: in short, theirs was a myeloma resistant to therapies and difficult to treat. The results of the trial are very encouraging: the response to the treatment, in both groups of patients, was around 73%; in almost a third of the patients the tumor was no longer detectable, while for 60% of them it had shrunk very significantly, although it had not disappeared completely. Not bad, considering that the other treatments had failed: “These results”, explained Ajai Chari, director of clinical research at the Multiple Myeloma Program of the Tisch Cancer Institute and head of the trials, “indicate that at least three quarters of patients have a new perspective of life. Talquetamab induced a strong response in patients with relapsed or refractory multiple myeloma, the second most common blood cancer. It is the first bispecific agent that targets the GPRC5d protein [un recettore presente sulla superficie delle cellule tumorali, nda] in patients with this disease.