– In Poland we are in a happy and unhappy situation. On the one hand, patients with progression or relapse of HL after the ASCT procedure have access to new drugs, on the other hand, we are still waiting for the possibility of consolidation treatment following the applicable standards of care. With the hematologist prof. Tomasz Wróbel, we talk about Hodgkin’s lymphoma.
Professor, Hodgkin’s lymphoma is a rare malignant tumor. What is its specificity?
It is quite a rare neoplasm, belonging to the group of cancers of the lymphatic system. Its name comes from the name of an English doctor – Thomas Hodgkin, who was the first to describe the characteristic disease affecting the lymph nodes. It differs from other lymphomas in the histopathological picture, but its most important characteristic feature is its occurrence at a young age.
We can talk about two peak incidence – the highest occurs in people between 20 and 35 years of age, that is, in people at the beginning of their family and professional path. This is an extremely important aspect that we must take into account when proposing treatment to patients.
What are the risk factors for developing HL?
They are not clearly defined. It has been shown that same-sex siblings with HL have a higher risk of developing the disease. Interestingly, while the incidence of lymphoma in developed societies is increasing, which is probably associated with an aging population and environmental pollution, the incidence of Hodgkin’s lymphoma is relatively constant.
What symptoms should worry us?
The main symptom of the disease is painless enlargement of the lymph nodes. In 30 percent Additionally, patients develop other symptoms: fever, drenching night sweats, weight loss, sometimes itchy skin.
The basis of the diagnosis is the histopathological examination?
Yes, but this is just the beginning of the road – the diagnosis must always be supplemented with an assessment of the severity of the disease. According to the Ann Arbor classification, on the basis of the number and location of the nodal areas affected by the tumor, we can distinguish four stages: I, II, III and IV.
The border on the basis of which we distinguish the various stages is the diaphragm. If nodal changes occur on one side of the diaphragm, it is referred to as the early stages (I or II), while if the nodal changes occur on both sides of the diaphragm, they are referred to as advanced stages (III and IV).
At what stage of the disease do patients most often report?
In Poland, as in other countries, 60-70 percent. patients are reported in the earlier stages, while 30-40 percent. in advanced stages. A typical example of a patient is a 29-30 year old woman who comes to the doctor for enlarged lymph nodes in the neck. Most often there is also a lesion in the mediastinum – so it is stage II.
What is the prognosis of patients diagnosed with Hodgkin’s lymphoma?
Successful – we manage to heal over 80% of patients. This is usually achieved with chemotherapy or a combination of chemotherapy and radiation therapy. It is very important to recognize the disease as early as possible.
What changes for patients with Hodgkin’s lymphoma have recently appeared in Polish and international guidelines for diagnostic and therapeutic management in patients with neoplasms of the haematopoietic and lymphatic systems?
In recent years, PET-CT (Positron Emission Tomography) has been gaining more and more prognostic importance, which allows us to determine the advancement of the disease in a very reliable way. This is important both in determining the stage and later in monitoring the effectiveness of the therapy. As I said, the histopathological picture of Hodgkin’s lymphoma differs from that of other lymphomas.
If we look at the patient’s lymph node, the characteristic, giant Reed-Sternberg (RS) neoplastic cells are only 1-2 percent, and the main mass of the tumor is activated cells of the lymphatic system. Due to the fact that the lymphatic system is so stimulated, it “shines” perfectly in the PET examination. However, when it comes to changes in therapy, the priority is to find a balance between the effectiveness of treatment and its toxicity.
So we have to meet two essential factors, firstly, to obtain a cure, and secondly, to avoid late complications from the heart and the occurrence of further cancers. Here, once again, the PET-CT examination comes in handy. Already after two cycles of chemotherapy, we perform the so-called early PET assessment, which allows us to find a group of patients with good prognosis and not requiring treatment intensification, as well as those with poor prognosis.
What treatment options are offered to patients with a lack of response to first-line treatment?
In the case of patients refractory to treatment or relapsing, we must use stronger tools, the so-called megachemotherapy. Unfortunately, the stronger the chemotherapy, the greater the toxicity, and the toxicity we fear most is irreversible damage to the bone marrow.
Therefore, before administering megachemotherapy to the patient, we collect hematopoietic stem cells from the patient. The stem cells taken from the patient are first frozen in liquid nitrogen and then transferred back after megachemotherapy. This is a type of transplant in which the patient is both the recipient and the donor.
What is the prognosis for patients with progression or recurrence of HL after the ASCT procedure?
The use of mega-chemotherapy assisted by autologous hematopoietic cell transplantation (ASCT) allows us to cure 50-60% of cancer patients. patients with relapsed / refractory form of HL. The best results are obtained in people with late relapse (> 12 months) and with preserved chemosensitivity.
Unfortunately, in the case of high-risk patients, i.e. those who have not achieved remission, who have relapsed within less than 12 months of completing first-line treatment, or who have infiltrates beyond the lymph nodes in the case of relapse, this method is not sufficient. Worse still, in the case of subsequent relapses, the prognosis is unfavorable with a median survival not exceeding 2 years.
Are there any therapeutic strategies to lower the risk of relapse?
Yes, in recent years, “targeted drugs” have appeared that give patients a chance. One of them is a drug that targets the CD30 antigen, which is typical of Hodgkin’s lymphoma. The drug contains a monoclonal antibody linked to a cytostatics. Its use in patients who have relapsed after autotransplantation has resulted in a response rate of up to 70%.
A drug targeting the CD30 antigen was the subject of the AETHERA study – what hope do the results bring for HL patients?
The main objective of the study was to investigate the possibility of using a CD30 antigen monotherapy to prolong progression-free survival after autologous stem cell transplantation in patients with Hodgkin’s lymphoma who had at least one risk factor for disease progression.
After transplantation, patients were divided into two groups: one received the drug and the other placebo. It turned out that administration of a drug containing a monoclonal antibody combined with a cytostatic after autotransplantation as maintenance treatment reduces the risk of progression by almost half. As a result, consolidation treatment was included in the recommendations of many international societies and became the standard of care.
What exactly is consolidation therapy?
The basis of consolidation therapy is the assumption that patients with relapsed or refractory Hodgkin’s lymphoma are not a homogeneous group. We can cure most of them with the aid of mega-chemotherapy and autologous transplantation. However, we must remember that in some patients, even such a strong treatment is insufficient. We try to identify such patients using the risk factors discussed above.
Logic dictates that additional forms of treatment should be used when expecting an insufficient effect of mega-chemotherapy. Hence the idea of consolidation therapy administered after mega chemotherapy. A monoclonal antibody is well suited for this type of procedure, as it is a relatively low-toxic drug as a form of targeted therapy.
What can Polish patients with progression or recurrence of HL count on after the ASCT procedure?
In Poland, we are in a happy and unhappy situation. On the one hand, patients with progression or relapse of HL after the ASCT procedure have access to new drugs, which means that we can offer them a good standard of treatment.
However, there is still no possibility of administering consolidation treatment after ASCT. Currently, this is an unmet clinical need today, especially since we are talking about young people and a small group of patients. The use of consolidation in high-risk patients would reduce the risk of cancer recurrence, and thus save a significant group of patients from avoiding further lines of therapy.