There are just over 400 Italians who receive a diagnosis of acute lymphoblastic leukemia every year, a rare form of blood and bone marrow cancer that often progresses rapidly and if left untreated it can lead to death within days or weeks. Today, patients are being treated on the front line with different intensive chemotherapy regimens in order to achieve and maintain complete remission of the disease. For the first time, however, the results of two Italian studies presented at the congress of the European Society of Hematology (Eha) in recent days, advance the hypothesis of a “chemo-free” therapy with the use of a new immunotherapy drug, blinatumumab, already used in Italy for patients who do not respond to conventional treatments or who have had a relapse despite the use of previous treatments. Both trials were conducted by the Italian Group of Adult Hematological Diseases (GIMEMA): the GIMEMA LAL 2116 D-ALBA study paves the way for chemotherapy-free treatment using first-line blinatumomab in adult patients with Philadelphia-positive acute lymphoblastic leukemia; while the results of the GIMEMA LAL 2317 trial demonstrate, for the first time, the first-line efficacy of blinatumomab, in addition to chemotherapy, in eradicating minimal residual disease in adult patients with Philadelphia chromosome negative acute lymphoblastic leukemia.
The current standard therapy
The current standard treatment for this neoplasm is chemotherapy, administered in cycles of three phases: that of induction, with the aim of eliminating most of the leukemic cells; that of consolidation, which aims to destroy the residual leukemic cells and the maintenance phase, which has the aim of preventing the reappearance of new leukemia cells and therefore the recovery of the disease in patients who respond to the first two phases. In high-risk patients who are unresponsive to induction chemotherapy or who relapse shortly after therapy, allogeneic transplantation is the treatment of choice. (from a donor other than the patient) of hematopoietic stem cells. «It is not a very frequent disease, but extremely serious – he explains Renato Bassan, director of Hematology at the AULSS3 Serenissima in Venice – and in the oncohematological field it has always been an avant-garde environment for experimenting with new drugs and treatment strategies. This has meant that there has been a lot of progress, more in children than in adults: in the last decade some novelties have entered the therapeutic armamentarium that have been added to chemotherapy and transplants which are progressively leading to an increase in the cure rates in groups of patients of different ages ».
Treatment without chemo
30% of adult patients with acute lymphoblastic leukemia express a positive Philadelphia chromosomal alteration (in Italy there are about 130 new cases per year) which determines a particularly aggressive prognosis and with high risk of relapse. An update of the results of the GIMEMA LAL 2116 D-ALBA study (already published last October in the prestigious New England Journal of Medicine) and indicate the benefits obtained by patients with a longer observation period. «The new treatment protocol pioneered in the trial sees administration of blinatumomab together with a tyrosine kinase inhibitor and steroids, with two main advantages for people – continues Bassan -: greater ease of use than chemotherapeutic drugs, which involve important toxicities and avoiding allogeneic donor transplantation in an important percentage of patients. And this is also a considerable step forward in terms of reduction of toxicity“. The data relating to 63 patients (mean age 54 years) confirm a high rate of molecular responses and it emerges that 80% are free from disease and alive at two years and 90% of these have reached a ‘minimal residual disease’ negativity rate, a small number of leukemia cells potentially capable of triggering a disease recurrence: in practice, if after the first course of treatments there is really no trace of the tumor (i.e. there is no residue), the hopes of definitive recovery are greater, as well as the chances of being candidates for transplantation are higher. for patients who need it.
Philadelphia negative leukemia
The prognosis of adult patients with negative Philadelphia acute lymphoblastic leukemia (about 300 new cases per year in our country) has also improved significantly in recent years, especially thanks to therapies aimed at eradicating the minimal residual disease. For these patients the GIMEMA LAL 2317 trial provided forIncorporate two courses of blinatumomab in addition to chemotherapy into first-line treatment, with the aim of improving responses (in terms of minimal residual disease) and prolonging patient survival. 149 patients (mean age 41 years) were enrolled in all major Italian haematologies, of which almost half were at high or very high risk of relapse. After a single course of blinatumomab, eradication of residual disease increased from 73% to 96%. At one year, 83.8% of patients were alive and 71.6% were disease-free. «This large study confirmed the improvement of the parameters that we wanted to improve – concludes Bassan -. Having shown over the years to be a very promising drug in relapses, it was decided to use blinatumomab also in a first-line treatment. The GIMEMA LAL 2317 trial is of considerable importance because it is the first study in the world concluded, with published data (such as abstract at the Eha 2021 congress) onuse of blinatumomab in first-line therapy“. Blinatumomab is a bispecific monoclonal antibody, belongs to the category of so-called BiTE (the acronym stands for Bi-specific T-cell engagers antibodies) and is the progenitor of dual target antibodies (hence the term “bispecifici»), Drugs that enhance the antitumor activity of the immune system: their characteristic is lock onto two targets, building a sort of bridge that connects the T cells, the most powerful agents of the immune system, to the cancer cells that are the target to be hit. Thanks to this bridge, T cells can act at close range on cancer cells, recognizing them, binding to specific antigens and releasing molecules that cause their death.
July 1, 2021 (change July 1, 2021 | 17:38)
© REPRODUCTION RESERVED