After thirty years of desert, in which only chemotherapy was available, in the last five years a shower of innovative therapies has arrived that are radically changing the possibilities of treating leukemia and other blood cancers. It is a very positive message what it comes from Leukemia 2021, the 10th National Conference on leukemia promoted byItalian Association against leukemia, lymphomas and myeloma (Ail), which aims to trace the state of the art on advances and on the new frontiers of research in hematology. The main changes concern the acute myeloid leukemia, where we are witnessing a sort of paradigm shift: increasingly personalized drugs are combined with a “good for all” treatment. A concept that seemed abandoned and that recalls that of the old chemotherapy, with the big difference that now the drugs are all “intelligent”, precisely, and only target diseased cells.
“It’s a time of great innovation,” he says Giovanni Martinelli, Scientific Director of the Romagna Institute for the Study of Tumors: “In recent years, at least 6 new very effective medicines have obtained registration, with high response rates, all strongly targeted on molecular targets and mechanisms or mutations, and others are coming” . The premise is that leukemias can be very different from individual to individual, even more than in other cancers and this has strongly pushed towards a new generation of target drugs. At the same time, however, there has been something of a turnaround in the past three years: the combination of two drugs that work by de-energizing the cancer cell and that work in many types of myeloid leukemia has replaced chemotherapy in the elderly and in the adults with relapses. “And the results are so positive that we are thinking of using this scheme in progressively younger patients”, explains Martinelli: “We are then back to doing what I thought we had now abandoned, it is the new ‘one fits all’. The protocol it was published a few months ago in the New England Journal of Medicine ”.
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The two drugs are venetoclax and azacitidine: the first binds to a specific protein called (Bcl-2), the second is a hypomethylating agent. Together they are able to give lasting remissions in most patients. “We are conducting a real life study together with other centers and the first data are really encouraging”, continues the hematologist: “More than half of the patients have a complete remission. We are talking about people over 85 years old or heavily pretreated and relapsed several times: unimaginable results only a few years ago “.
The leukemic cell does not use the same energy pathway as healthy cells, but an alternative pathway is created, which this therapeutic strategy aims at, which is why the toxicity of these drugs is much more manageable than that of chemotherapy. It is therefore always a precision therapy: not personalized, but aimed at a signal path. “The combination creates an energy catastrophe for the sick cell: it is like pulling down the switch on the general panel instead of unplugging the individual plugs”, says Martinelli: “At the same time, however, we are adding to this combination other target and individualized medicines that make the treatment even more effective. At the Meldola Center we have several ongoing clinical trials.
At the same time, we realized that we are probably using the combination excessively: we do too many cycles, too close together and perhaps with excessive doses of drugs, weakening the immune defenses of the most fragile patients and thus exposing them to a risk of infections. I believe that in the coming months another dogma will be broken, with the demonstration that many cycles are not needed ”.
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Scientific research is very active in Italy, as he points out Sergio Amadori, Ail national president: “In particular the GIMEMA cooperator group, born from an enlightened idea of Professor Franco Mandelli to create a network of all Italian hematology centers, has made it possible to conduct studies that have represented a turning point in the treatment of some forms of blood cancer ”. An example concerns acute Ph + lymphoblastic leukemia, or acute lymphoid treated with a chemo-free program, based on the use of cortisones and a tyrosine kinase inhibitor, dasatinib: “The recently published study showed that the dasatinib-corticosteroid combination is able to allow complete remission of the disease in over 95% of cases with a very significant quality of induced remissions “.
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Another important step forward was the use of a so-called bispecific antibody, blinatumomab: after the initial phase of treatment with dasatinib and corticosteroids, patients are treated with 2-5 cycles of blinatumomab which has the task of reducing the amount of leukemia cells left in the body. “This GIMEMA protocol – concludes Amadori – without chemotherapy and with blinatumomab, is giving such brilliant results as to become a standard of care for patients with this Ph + leukemic form”.
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