Myelomas

Bone marrow biopsy and bone marrow needle aspiration aim to check whether there are tumor plasma cells in the bone marrow..

If more than 10% of all cells in the bone marrow are present, the diagnosis of multiple myeloma is confirmed. If they are present in amounts less than 10 percent, we speak of monoclonal gammopathy of uncertain MGUS significance, a nonpathological condition requiring no treatment.

The procedure is performed on an outpatient basis under local anesthesia and consists of aspirating a few milliliters of marrow blood and taking a small bone fragment from the pelvis . Specimens are sent to anatomic pathology for evaluation.

In addition to histologic examination and immunophenotype, which are used to quantify the number of plasma cells and assess their characteristics, with bone marrow needle aspiration a cytogenetic examination (called FISH) that assesses the presence or absence of certain chromosomal alterations in plasma cells that confer more aggressive features of the disease. This examination is essential to define the stage of the disease.

In cases where an isolated plasmacytoma, i.e., an accumulation of tumor plasma cells in a single bone area or other organ without widespread bone marrow involvement, is suspected, a sample of the lesion itself should be taken by biopsy to perform histological examination and confirm the diagnosis.

If, on the other hand,amyloidosis is suspected, physicians may request a biopsy of the periumbilical fat or minor salivary glands, areas where the abnormal protein produced by plasma cells (the so-called amyloid substance) tends to accumulate. Periumbilical fat biopsy is a simple and quick procedure that is performed on an outpatient basis, without anesthesia, by taking small fragments of fat tissue near the umbilicus. Instead, salivary gland biopsy is performed by the otolaryngologist.

In rarer cases, amyloid substance may be sought directly in the suspected organ of accumulation, such as the kidney, intestine, or stomach, by targeted biopsy.

Several instrumental examinations can be performed to go for the typical bone lesions of multiple myeloma, called osteolytic lesions:

• the first examination that is requested is a CT scan (computed axial tomography) of the whole body with low-dose radiation without contrast medium that examines all skeletal body segments looking for such lesions;
• as an alternative to CT, the physician may request a CT-PET (positron emission tomography) scan, which has the same function and identifies bone lesions as “metabolically active” areas. PET-CT requires the use of a radiolabeled glucose contrast agent. PET-CT has the advantage of being able to assess disease response during treatment, which is more difficult to assess with CT alone;
• In addition to or as an alternative to either of these examinations, the physician may request an MRI of the spine and pelvis or the whole body without contrast medium, a longer examination but one with greater sensitivity than a CT scan.

The choice between one of these three tests is determined by the physician based on the characteristics of the patient and the disease.

Immunotherapy involves the use of drugs that can fight the disease using mechanisms similar to those of the immune system, or restoring the patient’s immune system’s ability to attack and destroy cancer cells.

Immunotherapy drugs used in the treatment of multiple myeloma are:

• monoclonal antibodies: antibodies similar to those produced by our body to fight infection, they are, however, produced in the laboratory to “recognize” and target certain markers found mainly on cancer cells. Once bound to the target they induce destruction of the diseased cell;
• immunoconjugated drugs: monoclonal antibodies to which substances toxic to the cancer cell have been combined in the laboratory. Once administered, the antibodies recognize the markers on the cancer cells, bind to them and “dump” the toxic substance into the cancer cell, causing its death;
• Bispecific antibodies: antibodies trained to recognize two markers simultaneously, one present on tumor cells and one present on healthy cells in the patient’s immune system. The diseased cell and the healthy cell are then “approached,” and the healthy cell is induced by the drug to attack and destroy the diseased cell;
• CAR-T cell therapy: these cells represent one of the newest innovations in the treatment of multiple myeloma. The therapy is carried out by taking the patient’s immune system cells (particularly T lymphocytes) from his or her blood, which are sent to a laboratory where they are “trained” to fight the tumor. Specifically, they are induced to express antibodies on their surface directed against a specific marker present on the tumor. The lymphocytes are then reinfused via normal IV into the patient’s bloodstream so that they can target the cancer cells, recognize them, and destroy them. This type of therapy is performed with a single infusion and is done on an inpatient basis to monitor side effects caused by inflammation due to the administration of the therapy.

Biologic drugs are drugs that can block certain signaling pathways of the cancer cell inducing its destruction.

This includes proteasome inhibitors such as bortezomib and carfilzomib and immunomodulating agents such as thalidomide, lenalidomide and pomalidomide.

Chemotherapy includes drugs that eliminate cancer cells by exploiting their faster rate of reproduction than healthy ones.

Because it interferes with the replication mechanisms of cells, chemotherapy also damages the body’s healthy cells, causing side effects that fortunately disappear once the treatment is over and are in any case well controlled with modern supportive therapies.

Stem cell autotransplantation is used to enable the use of high-dose chemotherapies, more potent than those normally administered, with the goal of eliminating as many cancer cells as possible.

Because these high-dose therapies can temporarily damage the bone marrow, which is the organ that produces blood cells, previously harvested stem cells are reinfused into the patient. In this way, the marrow can regenerate rapidly, re-establishing the production of red blood cells, white blood cells and platelets.

This type of therapy is performed on an inpatient basis, lasting an average of 3 weeks.

Radiation therapy is a treatment modality that uses high-energy radiation to destroy cancer cells..

In multiple myeloma, radiation therapy is used mainly for antalgic purposes, that is, to reduce pain caused by osteolytic lesions or tumor plasma cell masses.

It can also be used curatively and at higher doses in the treatment of plasmacytomas.

All patients with newly diagnosed multiple myeloma are offered therapy with monthly infusions of zoledronic acid (Zometa) for at least one year and up to two years after the start of treatment.

This drug is used to strengthen bones affected by the osteolytic lesions of myeloma to prevent the occurrence of pathological fractures.

In order to receive zoledronic acid, good kidney function and a dental evaluation to rule out caries or ongoing dental infections are required. These, in fact, increase the risk of mandibular osteonecrosis, a side effect that may rarely occur while taking the drug.

Therapy for patients who are candidates for stem cell autotransplantation has several steps, using combinations of drugs to achieve maximum efficacy against cancer plasma cells:

The first phase, called induction, involves the administration of three or four biological and immunotherapeutic drugs with the goal of rapidly eliminating most of the cancer cells. When the patient’s condition permits, induction can be done in day hospital, with drugs administered by nurses subcutaneously or intravenously and oral medications taken at home. The most effective combination currently uses the monoclonal antibody daratumumab, along with bortezomib, thalidomide and cortisone, for four cycles of 28 days each.

After induction is completed, autologous hematopoietic stem cells, that is, precursor cells of all blood components from the same patient, are collected. The collection is done through a procedure called staminopheresis, similar to a long blood donation, which is noninvasive and can be done on an outpatient or inpatient basis.

After collection, the patient is admitted for autologous transplantation. During hospitalization, high-dose chemotherapy with melphalan is administered to eliminate any remaining plasma cells. Next, the harvested stem cells are reinfused, in a procedure similar to a transfusion, to accelerate marrow recovery and the production of red blood cells, white blood cells, and platelets.

Two rounds of consolidation, similar to the induction phase, may be administered after discharge to reinforce the therapeutic response. Finally, maintenance therapy with a nonchemotherapy biological drug, taken orally at home, is proposed to prolong disease remission. During this phase, the patient has periodic day hospital checkups at progressively longer intervals to monitor the disease status and clinical condition.

Patients who are ineligible for autologous transplantation are offered combinations of two or three immunotherapy and biologic drugs administered on an outpatient basis by trained nurses.

Age alone is not a sufficient criterion for defining the optimal type of therapy for the specific patient; associated diseases, degree of functional autonomy, and presence of caregivers are also taken into consideration.

Each option is discussed always taking into consideration the patient’s wishes and preferences.

Multiple myeloma can be considered as a chronic disease, which alternates between periods of disease remission and relapses or relapses requiring new treatments.

Fortunately, there are many therapeutic options even for relapsed myeloma: these always include combinations of immunotherapeutic and biologic drugs, usually different from those used at diagnosis, precisely to go after the cancer cell at different targets.

Chemotherapy, on the other hand, plays a very marginal role in relapsed myeloma and is rarely used.

There are cases in which tumor plasma cells are present that are not associated with the presence of the typical signs and symptoms of multiple myeloma.

In these cases, we speak of asymptomatic or “smoldering” multiple myeloma, which requires no treatment but only periodic monitoring of the monoclonal component and laboratory tests (every 3-6 months) and radiological monitoring with MRI (at least annually).

Asymptomatic myeloma is at risk of evolving to symptomatic myeloma, and the magnitude of the risk depends on several clinical and biological factors, based on which the cadence of follow-ups is set.

The goal is to go to intercept the evolution to symptomatic myeloma before serious changes in the examinations occur.

It is important to rememberthat there are patients with asymptomatic myeloma who will never develop symptoms and can continue with only progressively longer latency checks.

The therapy of choice for solitary plasmacytoma is radiation therapy.

Radiation therapy is administered in daily sessions Monday through Friday for several weeks, depending on the scheduled radiation dosage. Sessions usually last only a few minutes.

The drugs used in the treatment of amyloidosis are the same as those used in multiple myeloma.

The dose and intensity of therapies is carefully modulated according to the site of accumulation of the abnormal protein that is produced by diseased plasma cells.

Treatment requires multidisciplinary management that may involve the nephrologist, cardiologist, and/or gastroenterologist.

Treatment for multiple myeloma often involves side effects that impact quality of life more or less severely. However, they can be mitigated and in some cases prevented by specific treatments and/or appropriate lifestyle.

At the Candiolo Institute, the doctors and nurses of the multidisciplinary team are available to provide the patient with all the support he or she needs to manage the various side effects he or she will face in the course of treatment.

To ensure timely and direct support and receive timely answers to concerns and questions, a dedicated helpline is in place at the Candiolo Institute for all patients.

From Monday to Friday, from 8 a.m. to 5 p.m., you can contact the secretariat of the oncology day hospital at 011.993.3775, reporting the need for urgent consultation.

The patient will be quickly put in touch with his or her medical specialist, to receive clear answers and immediate support.

The cancer patient is a person with complex needs that requires multidisciplinary support not only for the cancer disease, but also for all related issues.

At the Candiolo Institute, patients who need or require it have access to specialists in different areas to receive nutritional support, physical therapy, pain therapy and management of other associated conditions.

The Social Service Department of the Candiolo Institute conducts information and orientation interviews to patients and their families on how to access services in the area and how to obtain welfare and social security benefits provided by law (disability, benefits for aids and prostheses, work leave, etc.).

The service operates on Wednesdays and Fridays from 9 a.m. to 1 p.m. (phone: 011 9933059).

The response to treatment is first assessed by assaying the monoclonal component in serum and/or urine every cycle or every 2-3 cycles: if treatment is effective, the monoclonal component should in fact gradually go down until it is no longer detectable.

When the monoclonal component disappears or is reduced more than 90% , the physician may also request reevaluation with bone marrow needle aspiration to assess the reduction-in optimal cases the disappearance-of tumor plasma cells in the bone marrow. The latter evaluation is not mandatory in clinical practice, but it provides information about residual disease that may be useful from a prognostic point of view.

In addition, the physician will require in-process radiological reevaluation with the same examination performed at diagnosis (low-dose total body CT, CT-PET, or MRI). These examinations will be performed periodically during treatment with timings evaluated by the physician. Multiple myeloma therapies are almost all chronic, meaning they are continued continuously until disease relapse unless treatment toxicities are developed.

In the event of a relapse, usually detected by an increase in the monoclonal component associated or not with a recurrence of signs or symptoms of disease, the physician will request a new bone marrow biopsy with needle aspiration to re-quantify tumor plasma cells and assess the general condition of the bone marrow. In addition, a new radiological investigation will be carried out to identify potential new-onset osteolytic lesions.

Due to the high number of cases treated each year, the Candiolo Institute is a national reference for taking care of esophageal cancer. Our experience enables us to deal with even the most complex situations, always with a personalized approach built on the clinical and personal profile of each patient.

Establishing the treatment plan always starts with an accurate and timely diagnosis. Patients have access to state-of-the-art imaging technologies that allow accurate assessment of the extent of the disease.

In addition, the Institute offers advanced and sophisticated laboratory investigations, including molecular and genomic analyses, which are critical for identifying biological features of cancer and guiding therapeutic decisions.

As an IRCCS, the Candiolo Institute combines clinical practice with a strong vocation for scientific research. Patients can be evaluated for inclusion in active clinical trials, which provide a real opportunity to access innovative therapies not yet available in standard practice. Collaboration between care and research is a distinctive value that translates into concrete opportunities for the patient.

The Interdisciplinary Care Group takes care of the person at every stage: from diagnosis to treatment to follow-up, with attention to nutritional support, psychological health, and reintegration into daily life. The organization of checkups, examinations and treatment is designed to ensure continuity and serenity, always valuing the human dimension of care.