Myeloma: complex, recurrent, but can be lived with for many years. Resistant Patients Waiting for New Treatments

Anna had severe bone pains: her shoulder, her legs. It hurt so much that she wanted to tear her leg off to stop the pain. The morphology results were very good, but protein appeared in the urine, so the doctors recommended antibiotics: one, two, another. When the bone pain persisted, it was assumed that it was the result of neurosis or depression. Only after a year of going from doctor to doctor was she diagnosed with multiple myeloma. She was 40; this is hardly typical of this disease, which usually affects people around the age of 70. It is mainly a disease of the elderly, but 30-40-year-olds are also increasingly common. doctor hab. Dominik Dietfeld from the Department and Clinic of Hematology and Bone Marrow Transplantation of the Medical University. Karola Marcinkowski of Poznań, president of the Polish Myeloma Consortium, recalls a 30-year-old patient who was diagnosed after he broke his spine while picking up his wife at a wedding.

More remissions and more relapses

Myeloma is the second most common blood cancer. Until recently, the average life expectancy after diagnosis was about 3 years, now - thanks to new drugs and their combinations, which are many - patients live for several years, often without recurrence of the disease. They take care of their families, they work, they have their own hobbies. Carita Foundation Every year Wiesławy Adamiec organizes a bike ride for “myeloma patients”, the Foundation of the Myeloma Treatment Center in Krakow - meetings in the mountains: many patients treat myeloma so effectively.

Anna has been treated for 8 years; so far, whenever the disease recurred, she received a different therapy. – This is the specificity of myeloma: the disease returns, is in remission, but then recurs. It always recurs because it is currently an incurable disease, but periods of remission can be long. Patients are often on the second, third, fourth, fifth and subsequent lines of treatment, and yet, unlike many other types of cancer, they are often not in a palliative state. Many of them work and live normally. The condition, however, is access to further lines of treatment, further “puzzles” of drugs, because in myeloma the most effective are “puzzles” consisting of three or even four drugs from different groups, explains Dr. Grzegorz Dietfeld. The introduction of new therapies and their combinations is making myeloma patients’ lives longer and better.

Anna feels well, but lives in colossal stress.

- Every month I go to the hospital for a check-up, every month I am afraid of another relapse. Fear prevents me from functioning normally. At the Foundation, we are well educated, we know what drugs will be optimal for us, but doctors often shrug their shoulders, saying that they cannot use them. Clinical trials are the only chance, because there is no other direction of treatment that is optimal for me in the reimbursement system, says Anna.

New drugs - new opportunities

Thanks to modern and effective methods of treatment, myeloma is increasingly becoming a chronic disease. The selection of drugs must be individualized and meet the needs of the patient, so it is important to be able to choose - not only in the first line, but also in subsequent lines. - Myeloma has already become a chronic disease, we can treat it very well, but it is still an incurable disease, relapses are part of its natural course. We must have the tools to help patients also in the fourth or fifth line of treatment, confirms prof. Eva Leh-Maranda, National Hematology Consultant.

The January list of reimbursed drugs brought many positive changes. - This includes first-line supplementation for patients who are eligible for autologous transplantation: adding daratumumab to a lenalidomide and dexamethasone regimen; it also became possible to use lenalidomide as a maintenance therapy after transplantation. Lenalidomide has been successfully transferred to the chemotherapy catalog, so the availability of this drug is much higher. There is also a new antibody: elotuzumab - lists prof. Leh-Maranda.

An urgent problem is the growing drug resistance, especially to basic drugs such as bortezomib and lenalidomide, used at the initial stages of treatment; these drugs are used in most three-drug regimens. “This means that in patients diagnosed before 2018 and with renal complications, the options for further treatment are limited. All triple therapies currently available through the drug program contain bortezomib or lenalidomide. Among the patients I treat, this is about 60-70% of patients. The drug program provides good treatment for patients in the early stages of resistance. Unfortunately, after the 3rd line, where we work with patients at this later stage of the disease, access to modern therapies is significantly limited. Therapies that are lacking are isatuximab with pomalidomide, isatuximab with carfilzomib and dexamethasone, and daratumumab with carfilzomib and dexamethasone, adds Dr. Dietfeld.

“However, patients treated before 2018, when the only available new drug was lenalidomide, are in a difficult situation: we used it in a two-component system: lenalidomide and dexamethasone. The addition of a third drug indicated that the three drug regimen was more effective than the two drug regimen. However, when a patient was treated on a two-drug regimen, we will no longer use three-drug regimens,” explains Prof. Krzysztof Yiannopoulos, Head of the Department of Experimental Hemato-Oncology, Medical University of Lublin.

“If I had to say what the drugs lack the most today is the protection of patients in this more advanced form of the disease being treated in downstream lines. Such a drug is isatuximab, a monoclonal antibody registered for pomalidomide and dexamethasone, and the same therapy registered for carfilzomib and dexamethasone.

These triple therapies are recommended for patients refractory to lenalidomide and bortezomib. Ultimately, we would like the decision on the choice of therapy to depend on the knowledge of the doctor and be made jointly with the patient. We will certainly strive for such a situation, emphasizes Dr. Dietfeld.

Early diagnosis is important

The symptoms of myeloma are nonspecific, so the time to make a diagnosis can take from several months to several years. How early myeloma is diagnosed greatly affects a patient’s chances of starting treatment before complications have arisen. Although the disease affects the bone marrow, it hides under many masks. The first symptoms may be, for example, pathological fractures. Another symptom is kidney problems. Myeloma doctors recommend that you get tests that your doctor may order. Anemia can be an alarming symptom (it is worth checking the level of ferritin, vitamin B12 and folic acid), as well as an increased ESR.

About 2-2.5 thousand people visit Poland every year. new cases of myeloma, and only about 10,000 people are sick. These are estimates, no patient records. Currently, one of the studies carried out by the Polish Myeloma Consortium (POMOST) under the direction of Prof. Krzysztof Yiannopoulos has been commissioned to create a register of myeloma patients.