Multiple myeloma (MM) is a malignant disease characterized by neoplastic proliferative process of plasma cells, which mainly develop in the bone marrow. Relapsed refractory multiple myeloma (RRMM) is one of the most complex forms of this disease, which occurs after unsuccessful attempts of first-line therapy. This form of myeloma is characterized by the highest degree of resistance to traditional methods of treatment, which makes it a challenge for oncologists. RRMM includes frequently observed symptoms such as bone pain, anemia, hypercalcemia, renal failure and the presence of bone lesions. Due to the high variability of the disease course and response to therapeutic interventions, patient groups have different prognoses and require individualized approaches to treatment.
History of the disease and interesting historical facts
Multiple myeloma was first described in medical literature in 1848 by physician Rudolf Wertschow. However, the history of the disease is much deeper, and interesting facts about its difficulties in diagnosis and treatment have accumulated over many decades. In the early 20th century, multiple myeloma was considered virtually incurable and was little known in clinical practice. With the advent of chemotherapy in the mid-20th century, some successes began to be noted. In 1962, a treatment protocol using prednisolone and chlorambucil was introduced, which yielded some positive results. However, the use of these treatment regimens did not solve the problem of relapses. With the advent of new drugs such as bortezomib and lenalidomide, a new era in the treatment of multiple myeloma began with the hope of improving the prognosis for patients.
Epidemiology
The prevalence of multiple myeloma varies by region and population. According to Epidemiology of Plasma Cell Neoplasms, approximately 160,000 new cases of multiple myeloma are diagnosed worldwide each year. In the United States, the incidence is estimated to be approximately 7.5 cases per 100,000 people per year, making multiple myeloma the second most common blood cancer after lymphoma. The disease is more common in men than in women, with an overall ratio of 2:1. The average age at diagnosis is 65 years. Studies show that certain ethnic groups, such as African Americans, have a 2-3 times higher risk of developing myeloma compared to other population groups.
Genetic predisposition to this disease
Multiple myeloma is often associated with characteristic genetic changes that may predispose to the development of the disease. Studies show that in 90% cases, patients have genetic abnormalities such as translocations 14;16 and 14;20, as well as damage to chromosomes 1q and 17p. In particular, deletion of 17p is a significant marker indicating a worse prognosis. These genetic changes affect plasma cell proliferation and their resistance to therapy, which is important for understanding the pathogenesis of the disease. In addition, some polymorphisms in genes associated with the immune response are also considered as factors contributing to the development of RMMM.
Risk factors for the development of this disease
Risk factors that contribute to the development of multiple myeloma include the following:
- Age: The disease most often occurs in people over 65 years of age.
- Gender: Men are more prone to MM than women.
- Ethnicity: High incidence is seen among African Americans.
- Occupational factors: Working with chemicals such as benzene may increase the risk.
- Preexisting conditions: Conditions such as monoclonal gammopathy of undetermined significance (MGUS) may precede the development of multiple myeloma.
- Obesity: Being overweight is also a risk factor.
- Radiation exposure: Exposure to ionizing radiation is associated with increased morbidity.
Diagnosis of this disease
Diagnosis of multiple myeloma requires a comprehensive approach. The main symptoms of the disease include:
- Bone pain;
- Fatigue and weakness (anemia);
- Increased bone fragility;
- Hypercalcemia;
- Renal failure.
Laboratory tests include:
- A complete blood count may reveal anemia and thrombocytopenia;
- Biochemical blood test to determine creatinine and calcium levels;
- Protein immunofixation and serum electrophoresis for detection of monoclonal protein (protein M).
Radiological examinations such as X-rays, CT scans, and MRIs can detect bone lesions. Other diagnostic methods include myospinal puncture and trephine biopsy, which help assess the extent of bone marrow involvement. It is important to differentiate from other hematological diseases such as lymphoma, osteosarcoma, and osteoporosis.
Treatment
Treatment of multiple myeloma, especially its relapsed form, requires a multi-tiered approach. Common treatment strategies include:
- Chemotherapy;
- Irradiation;
- Stem cell transplant;
- Immunotherapy.
Pharmacological treatment includes the use of the following groups of drugs:
- Proteasome inhibitors (bortezomib, carfilzomib);
- Immunomodulatory drugs (lenalidomide, melphalan);
- Anti-CD38 antibodies (dalatsijumab);
- Monoclonal antibodies and other targeted agents.
Surgical treatment may be indicated in cases of large tumors that compress the spinal cord. Other treatments, such as plasmapheresis, are used to correct blood hyperviscosity or sepsis, as seen in patients with myeloma.
List of medications used to treat this disease
The main drugs used to treat multiple myeloma include:
- Bortezomib (Velcade);
- Lenalidomide (Revlimid);
- Daratumumab (Darzalex);
- Carfilzomib (Kyprolis);
- Melphalan;
- Prednisolone;
- Enposidase (Pomalyst).
Disease monitoring
MN monitoring ensures control over the effectiveness of treatment and detection of relapses. The main control stages include:
- Regular laboratory tests: hemoglobin level, creatinine level, calcium level;
- Periodic radiological examinations to assess bone health;
- Assessment of response to therapy according to the International Myeloma Working Group scale.
The prognosis for patients with RRMM depends on a number of factors, such as the presence of genetic aberrations, response to treatment, and the patient's overall health. Complications may include infectious processes that complicate the course of the disease, as well as side effects of chemotherapy.
Age-related features of the disease
Age has a significant impact on the course and prognosis of multiple myeloma. In young people, MM may be more aggressive, whereas in older people the disease often progresses less actively, but treatment may be limited due to comorbidities. Older patients tend to have a worse prognosis due to high levels of comorbidity and decreased resistance to therapeutic interventions. Younger patients often have a more stable response to therapy and can be treated with more aggressive protocols.
Questions and Answers
- What is relapsed refractory multiple myeloma?
RRMM is a form of multiple myeloma that occurs after first-line therapy has failed and is resistant to standard treatments. - What are the main symptoms of multiple myeloma?
The main symptoms include bone pain, anemia, hypercalcemia, renal failure and the presence of bone lesions. - How is multiple myeloma diagnosed?
Diagnosis includes a complete blood count, biochemistry, X-rays and other radiological studies, and a trephine biopsy to determine bone marrow involvement. - What treatment is offered for RRMM?
Treatment may include chemotherapy, radiation, stem cell transplantation, and immunotherapy, using a variety of pharmacological drugs. - What is the prognosis for patients with this disease?
Prognosis depends on a number of factors, including the presence of genetic abnormalities and the response to current therapy, but in most cases, RRMM has an aggressive course and requires constant monitoring.
