Multiple myeloma is a cancer that is still very difficult to diagnose. Dr. hab. n. med. Dominik Dytfeld from the Department and Clinic of Hemotology and Bone Marrow Transplantation, Medical University of Poznań, President of the Polish Myeloma Consortium.
Thanks to the development of medicine, some patients with myeloma live longer and longer, can we talk about multiple myeloma as a chronic disease?
Dr hab. n. med. Dominik Dytfeld: We would like myeloma to be a chronic disease, but it is definitely too early to say that. It is true that globally there is a certain population of myeloma patients with a life expectancy of 10 years, and with super-optimal treatment, even up to 15-20 years.
This is the case in the United States, where access to drugs is much better than in Poland. This is our goal and we are striving for it, but unfortunately it is too early for that. The average survival of a patient with myeloma in Poland is about 7 years, for a certain population of patients it is even 10 years. It is true that the new therapies have changed a lot and practically tripled the survival time of patients compared to 10-12 years ago, but in our country it is far too early to say that myeloma is a chronic disease.
Moreover, there is such a subpopulation of patients with myeloma, which accounts for roughly 20 percent. patients whose prognosis remains poor. Poor prognosis means that the patient will usually respond less or not at all to treatment. At the same time, the next line of treatment may also not work and in fact the lifetime of patients remains significantly shorter compared to the population of the so-called low risk.
Doctor, what does such a risk depend on?
It results not only from the patient’s age, naturally the older the patient, the worse his prognosis is, but also from various biological elements and features of the disease. From the perspective of the biology of the disease, we are talking about the so-called high cytogenetic risk.
This group of patients has certain cytogenetic abnormalities, making treatment more difficult and the therapeutic benefit for these patients worse than for low risk patients. Unfortunately, these patients live significantly shorter lives, and we cannot talk about myeloma as a chronic disease in their case.
What are cytogenetic disorders? Which of the cytogenetic disorders are associated with the worst prognosis?
As with all types of cancer, in multiple myeloma, a normal, normal cell develops a disorder that causes the cell to become a cancerous cell. Such disorders in the genetic material are called mutations, in the case of cancer we are dealing not with one mutation but with many different mutations. These mutations may be that the cancer cells multiply more or are more resistant to the drugs used, they are simply stronger.
At the moment, we recognize several such mutations: translocations, deletions, duplications, we evaluate them on the basis of cytogenetic tests. The FISH method performed by very experienced cytogenetics allows us to determine whether certain genetic disorders are present in a given material or not.
Simplifying it for the purposes of our discussion – thanks to this research, we can obtain information about the specifics of the disease. In the course of research on myeloma, it was noticed that certain mutations were associated with a worse prognosis and a higher risk. Such changes are called high-risk changes. These are deletions in chromosome 17 (del (17p); translocation t (4; 14), translocation t (14; 16) and disorders within chromosome 1 (1q21).
Do patients in Poland have access to such tests?
Unfortunately, not all are sick. First, we must remember that this method is relatively difficult and must be performed by experienced cytogeneticists. Moreover, cytogenetic tests are usually carried out in laboratories associated with Academic Centers and in patients who are treated there. There are no such workshops in smaller centers. These tests are quite expensive, although there are various financing options, e.g. by the National Health Fund or simply by the hospital where the patient is diagnosed and treated.
Each patient at the Department of Hematology in Poznań has such a cytogenetic test performed. It is similar in other academic centers. Unfortunately, in smaller centers it is a bit more difficult, although it is not impossible, remember that the material can be sent to the laboratory where the test can be performed.
Why is cytogenetic testing of myeloma patients so important?
A patient who, on the basis of tests, is diagnosed with the disorders mentioned above, requires more careful observation and is a patient of the so-called higher vigilance.
If a patient has any of these disorders and I know it, I will look at that patient more closely. I will be in a situation of greater alert in his case, because I know that this disease will not respond to my treatment as optimally as in a patient who does not have these mutations, or the response will be shorter. Moreover, the progression of this disease usually progresses more dynamically.
Finally, there are certain therapies that should be avoided in this group of patients, and there are certain therapeutic measures recommended for these patients. Knowledge is constantly developing and evolving, I personally believe that the current state of knowledge and access to drug therapies, at least the potential one, is so large that I can use the knowledge about specific cytogenetic disorders due to the optimal therapy for the patient.
Is there a dedicated treatment for patients with myeloma and high cytogenetic risk? How is it effective?
It is a complex topic. The first information is that certain drugs used in patients with myeloma with the presence of bad disorders worsen the prognosis. We also know that in patients with these mutations, it is recommended to perform double bone marrow transplantation as part of the first-line treatment. We have had this knowledge for a short time, and the research confirming this thesis was presented at the ASH Conference – the largest hematology conference in the world.
According to the study, the so-called tandem transplantation is good for disease in patients who have poor cytogenetic disorders and it can be said that they compensate for this risk. Unfortunately, transplants are usually dedicated to patients at the beginning of the disease, first, and secondly, only to younger patients in good general condition. Thus, the therapeutic option discussed applies to a smaller patient population.
Drugs that have a positive effect on cytogenetic disorders are so-called proteasome inhibitors. 3 substances are registered. In certain situations, these therapies improve the prognosis of patients with cytogenetic disorders. However, only one of them endures poor prognosis. Treatment of high-risk patients is a multifaceted problem.
If a patient has a poor cytogenetic risk and is receiving a proteasome inhibitor by infusion, compared to high-risk patients who do not receive it, the prognosis will be better, but still worse than that of patients who have the background risk. Thus, this treatment improves prognosis but does not correct it.
In contrast, a large study called Tourmaline-MM1 has shown that there is a treatment that has this potential. This study demonstrated that patients with myeloma and high cytogenetic risk treated with an oral proteasome inhibitor in combination therapy have the same prognosis as patients at standard risk. So this treatment actually compensates for the cytogenetic risk.
Why is the form of administration of the drug so important in patients with myeloma? Does it translate into the effectiveness of treating patients?
This is natural, an oral drug is just much more convenient than injections. In addition to the convenience, this form of drug administration allows the patient with myeloma to function in society. In the case of the oral form, the patient does not have to adjust his life to the disease. In addition, during a pandemic, oral therapy and no hospital visits are the best and safest treatment for patients.
Imagine a patient with myeloma, if his treatment is 1 tablet, he can live and work normally. The method of using this drug significantly influences the social roles of the patient, he or she can be a father, husband, employee, boss or neighbor. Being in hospital for injections, unfortunately, the patient has to give up social roles and people by nature want to fulfill them. Hence, the quality of life in oral myeloma patients is much higher.
Are Polish high-risk myeloma patients likely to benefit from the optimal treatment option?
Unfortunately not. In the case of myeloma, the struggle to obtain reimbursement for various drugs lasted for many years and is still ongoing. Certain therapies have greater access, while at the moment oral proteasome inhibitors are not reimbursed for patients in Poland. We are left to wait and hope for a change.