Diagnostic needs of plasmocytic myeloma patients and new approaches to Hodgkin's Lymphoma therapy

Plasmocytic myeloma is a rare hematopoietic neoplasm. Its course and prognosis depend on genetic factors, among others. Are high-risk patients currently being properly identified and given access to therapy?

Cytogenetic changes in patients with plasmocytic myeloma are one of the strongest prognostic factors to determine the clinical course of the disease. Patients at high cytogenetic risk are patients whose therapy is a major challenge despite the tremendous advances we have seen in recent years in treatment. Cytogenetic changes are our most important concern.

In predicting the clinical course of myeloma, we rely on the revised International Prognostic Index, which includes questions of cytogenetic changes, among others. A new version of this indicator has recently emerged, which takes into account new cytogenetic changes. This is primarily a matter of the presence of a deletion within chromosome 17, but also changes within chromosome 1. Amplification, or addition, or 1q+ are additional genetic factors that have been included in this indicator. Changes within chromosome 14 are also an issue that has prognostic significance in plasmocytic myeloma patients. This is important because the chance of survival between low-risk and high-risk patients varies significantly. The expected patient survival time in high-risk patients is 38 months. This translates into the strategy we adopt. We are not always able to individualize treatment, but in some cases we can do so. Patients in Poland are treated under the so-called drug program. This means that the drugs we administer are reimbursed by the National Health Fund for strictly defined clinical conditions and indications.

We have a therapy that nullifies the adverse effect of cytogenetic changes. This is a regimen: ixazomide, lenalidomide, dexamethasone, or IRD for short. Studies show that its use is effective, regardless of the presence of genetic risk factors, in patients with relapsed forms. For us to use this treatment effectively, we need to have a cytogenetic study done and take into account current knowledge of cytogenetic risk. These factors related to changes within chromosome 14 are recognized factors. Lesions within chromosome 1 are a novelty that is not yet included in our program, but should be, because there are many such patients. With this knowledge, patients can be treated more effectively. The most important thing is genetic diagnosis, and the current recommendations are that every newly diagnosed patient with plasmocytic myeloma should have a genetic test, the so-called FISH (fluorescence in situ hybridization) test. This should be the standard of care at this point, in order to identify high-risk patients and determine the international prognostic index properly.

Hodgkin's lymphoma is a rare neoplasm of the lymphatic system of B-cell origin. It is characterized by the presence of a small number of neoplastic cells that are surrounded by an infiltration of cells of the immune system. Are patients with Hodgkin's lymphoma in advanced stages of the disease (III and IV) currently being treated optimally?

Until recently, I would have answered yes. However, medical knowledge has the ability to surprise, and progress in this area has also been great. The final results of a study comparing standards of treatment for patients were recently released. The ABVD standard, which has been in effect for about 10 years, consists of the cytostatic drugs doxorubicin, bleomycin, vinblastine and dacarbazine. It was compared to a new treatment that uses an anti-CD30 monoclonal antibody instead of bleomycin: brentuximab vedotin. It targets an antigen present on lymphoma cells. It also carries a cytostat: auristatin. In patients with advanced Hodgkin's lymphoma (stages III and IV) who have diffuse lesions on both sides of the diaphragm, the current standard was compared to the brentuximab vedotin + AVD standard, and a benefit was found not only in terms of time to progression, but also overall survival. This is extremely significant and rarely achieved in this disease. It shows us that chemo and immunotherapy is superior to plain chemotherapy. The results of this study have changed the way we think about treating the advanced form of this disease. Brentuximab vedotin is reimbursed in Poland, but for patients in relapse. Its first effects described in the study were on relapsed patients, and in them it is effective. It is not reimbursed in Poland for first-line treatment. This leaves some room for supplementation. In hematology, and probably not only in hematology, it is mostly the case that new molecules are first tested in relapsed and refractory forms, and when they have proven efficacy they are moved to earlier lines of treatment. It is usually the case that if a molecule shows activity in relapsed patients, it is even more effective if used earlier. And here it is indeed the case that in relapse it was used in monotherapy, and now we know that if we combine it with chemotherapy in the first line, we get better results than after chemotherapy alone. This is important because we can cure more patients, so there will be fewer patients with relapse and resistance. It's always a difficult situation for patients, and most of them are young people, at an age where they are starting families, want to have children, work and grow. For them, recovery from this disease is especially important. For the health care system, it's also important, because if we cure most patients with first-line treatment, we won't have to deal with the problems of treating relapses, resistance and using complicated therapies.