In an interview with InFo ONCOLOGY & HEMATOLOGY, Prof. Christoph Driessen, MD, Head Physician of the Department of Oncology/Hematology at the Cantonal Hospital St. Gallen, provides information on the pathogenesis, diagnosis and therapy in the field of non-Hodgkin’s lymphomas (NHL). Specifically, he addresses multiple myeloma and discusses the treatment goals and research innovations that will define future drug therapy.
Prof. Driessen, what role do oncogenic viruses and bacteria play in the development of non-Hodgkin’s lymphoma (NHL)?
Prof. Driessen: We have relatively little confirmed information on this. We know that some NHL are associated with viral diseases and we also find viral genomes, e.g. Epstein-Barr virus (EBV), in different cells in Hodgkin’s and non-Hodgkin’s diseases with different frequencies. But we cannot say that the development of the disease has its origin in viral infections.
For bacteria, there is no definitive evidence of an association of ontogeny between lymphomas and bacterial diseases in our geographic area.
Which histological and imaging examination methods are mandatory to obtain a confirmed diagnosis?
Two things need to be distinguished: We need to make a diagnosis per se and a diagnosis of spread.
For the diagnosis, one still needs a meaningful histology, i.e. one usually has to obtain a lymph node or tissue. Fine needle aspiration is usually not sufficient.
For propagation diagnostics, a whole-body cross-sectional imaging procedure is certainly still the standard in NHL. This is usually a CT scan, sometimes an MR scan. PET examination is very sensitive for spread diagnosis and is gaining more and more clinical importance. At the moment, however, this is not a standard diagnostic procedure that is absolutely necessary. In unclear cases, it is nevertheless a very helpful procedure. In addition, an examination of the bone marrow by means of bone marrow cytology and histology continues to be a standard part of NHL. However, at least in highly malignant NHL, it has been clearly demonstrated that if PET diagnosis was performed and it was negative with respect to bone marrow signal, bone marrow cytology/histology can be omitted.
CNS imaging and CSF examination is actually not performed as standard practice if, first, the patient does not have an appropriate clinic suggesting it or, second, does not belong to a specific at-risk population where CNS involvement is known to be common.
In which forms and with the help of which treatment methods is there a chance of a complete cure?
In principle, there is a chance of cure for highly malignant, fast-growing NHL. Thus, therapy is performed with the goal of a definitive cure, which includes poly-chemotherapy along with an antibody. In most NHL diseases, the R-CHOP regimen or related therapies are used here. Thus, a definitive cure can be achieved in the majority of cases. If it fails, cure is possible with higher-dose or other chemotherapy along with autologous stem cell transplantation, even in the relapse situation. Allogeneic transplantation is another procedure that can achieve definitive cures, but only in very selected cases, usually after failure of multiple therapies.
In low-malignant NHL, primary therapy has no curative claim, i.e., the primary goal is not to cure the patient of the disease forever. However, the treatments that are used are similar. Only in selected cases is there a possibility of nevertheless achieving a cure by means of an allogeneic stem cell transplant, but with very large individual risks.
An aggressive non-Hodgkin’s lymphoma of B lymphocytes is multiple myeloma. Different types (with IgG, IgA, IgD, Bence-Jones proteins) can be characterized here. How does the therapy differ in each case?
The subtypes of multiple myeloma are defined mainly on the basis of their genetic background, i.e. the change in the genetic material of these cells. The type of immunoglobulin secreted has no relevance to the choice of therapy.
Based on the genetic profile and clinical and serological markers, multiple myeloma can be distinguished as standard risk, higher risk, and peak risk. These distinctions are currently still under discussion internationally. There are some points where you are certain that it is very high risk, but for everything in between, there are different opinions on exactly how to categorize it. Risk-adapted therapeutic approaches are being explored, but we have no definitive proof that a specific therapy and only that therapy needs to be used for specific risk constellations. One exception may be translocation (4;14), which we know has been previously associated with unfavorable risk but has a standard risk outcome when bortezomib (Velcade®) is used in first-line therapy. So the risk constellation can be overcome with this drug.
Multiple myeloma is not curable. What are realistic goals that can be achieved with current therapy methods?
The goals, of course, depend on the patient and the disease. In younger patients or in patients up to 65 years of age who are eligible for high-dose therapy, the goal is to prolong statistical survival with the least possible impact of therapy on quality of life. Specifically, this means the longest possible therapy-free interval after primary therapy and controlled toxicity.
Even in the “elderly fit” patients who are not eligible for high-dose therapy, the goal is to prolong statistical survival and avoid myeloma-related complications while maintaining a good quality of life. For this, however, one does not use the high-dose treatment, but new drugs in combination. Thus, at least numerically similar results are achieved.
The third category is the “elderly-unfit” patients. Here we can no longer do more intensive therapy due to toxicity considerations. The goal here is clearly to avoid myeloma-related but also therapy-related complications and to optimize quality of life, but not to prolong overall survival. A low-toxic treatment is therefore applied.
Are there any innovations or research approaches in the therapeutic area of multiple myeloma that inspire hope?
There are very many approaches that give reason for hope. On the one hand, we have the new drugs that have been introduced, such as lenalidomide (Revlimid®) and bortezomib (Velcade®), all of which now have successor drugs from the same substance groups that are less toxic and in some cases still work when the first-generation drugs no longer do. Some of these drugs have already been approved by the EMA in the U.S. and others will be available in Switzerland in the foreseeable future. In the context of standard treatment, they currently are not.
In addition, many myeloma-specific antibodies are in development and will be launched in the next few years. There, I expect a similar change in the therapeutic landscape as was seen back then with the introduction of rituximab.
Immunotherapies are making great progress. In myeloma therapy, we have the situation where we achieve very good disease control initially but cannot control minimal residual disease. This is actually the best field of application for immunotherapies and I find the successes that have already been achieved here and that can be expected in the next few years very encouraging.
All of these new drugs, most of which are oral, have relatively few side effects and are valid options for all three patient groups described above.
In which patients is autologous or allogeneic stem cell transplantation indicated?
Autologous stem cell transplantation with high-dose chemotherapy is still the primary therapy of choice for patients who are biologically able to do so, usually those under 60, sometimes under 70.
Allogeneic stem cell transplantation in myeloma, as in other low-malignant myelomas, is a form of therapy that, in contrast to other treatment options, potentially offers a chance of cure, but is associated with very high individual risks. Overall, one tends to be cautious about the allogeneic form in multiple myeloma because the immunologic effects obtained with the foreign bone marrow are not as good as in other low-malignant lymphomas.
Currently, it looks like some patients with highest-risk multiple myeloma may benefit from tandem autologous/allogeneic transplantation in primary therapy.
Interview: Andreas Grossmann
InFo Oncology & Hematology 2013; 1(1): 30-32.
HAUSARZT PRAXIS 2014; 9(1): 61-63
