Multiple Myeloma

Bone marrow biopsy and bone marrow aspiration are performed to determine whether tumor plasma cells are present in the bone marrow.

If more than 10% of bone marrow cells are plasma cells, the diagnosis of multiple myeloma is confirmed. If plasma cells account for less than 10%, the condition is classified as monoclonal gammopathy of uncertain significance (MGUS), a non-pathological condition that does not require treatment but only clinical monitoring.

The procedure is performed on an outpatient basis under local anesthesia and consists of aspirating a small amount of bone marrow blood and obtaining a small bone fragment from the pelvis. Samples are then sent to anatomical pathology for evaluation.

In addition to histological examination and immunophenotyping, which allow quantification and characterization of plasma cells, bone marrow aspiration also enables cytogenetic analysis (FISH). This test identifies specific chromosomal abnormalities associated with more aggressive disease behavior and is essential for disease staging and risk assessment.

In cases where an isolated plasmacytoma is suspected, defined as a localized accumulation of tumor plasma cells in a single bone site or other organ without evidence of diffuse bone marrow involvement, a biopsy of the lesion itself is performed. This allows for histological confirmation of the diagnosis.

When amyloidosis is suspected, physicians may request a biopsy of periumbilical fat or minor salivary glands, as these are common sites where the abnormal protein produced by plasma cells (the amyloid substance) tends to accumulate.

The periumbilical fat biopsy is a simple, rapid, outpatient procedure performed without anesthesia, consisting of the removal of small fragments of fat tissue near the umbilicus. The salivary gland biopsy is instead performed by a specialist in ear, nose, and throat medicine (ENT).

In rarer cases, the amyloid substance may be detected directly in the affected organ, such as the kidney, intestine, or stomach, through a targeted biopsy.

Several imaging examinations are used to detect the typical bone lesions of multiple myeloma, known as osteolytic lesions.

The first-line examination is a whole-body low-dose CT scan (computed tomography) performed without contrast medium. This technique evaluates all skeletal regions to identify the presence of bone lesions.

As an alternative, a PET-CT scan (positron emission tomography combined with CT) may be performed. This examination identifies bone lesions as metabolically active areas and requires the administration of a radiolabeled glucose tracer. A key advantage of PET-CT is its ability to assess treatment response, which is more challenging to evaluate with CT alone.

In addition to or instead of these methods, an MRI (magnetic resonance imaging) of the spine and pelvis or a whole-body MRI may be requested. This examination is performed without contrast medium, takes longer to complete, but offers higher sensitivity compared to CT in detecting bone marrow involvement.

The choice among these imaging techniques is determined by the physician based on the patient’s characteristics and disease features.

Immunotherapy uses treatments that help the immune system recognize and attack cancer cells or restore the body’s natural ability to fight the disease.

The main immunotherapy approaches used in the treatment of multiple myeloma include:

• Monoclonal antibodies: laboratory-produced antibodies designed to recognize specific markers found on myeloma cells. Once they bind to their target, they trigger the destruction of the cancer cells.
• Antibody-drug conjugates (ADCs): monoclonal antibodies linked to substances that are toxic to cancer cells. After binding to their target on the tumor cell, they deliver the toxic agent directly into the cell, leading to its destruction.
• Bispecific antibodies: engineered antibodies that simultaneously recognize a marker on myeloma cells and a marker on immune cells. By bringing these cells into close contact, they stimulate the immune system to attack and eliminate the cancer cells.
• CAR T-cell therapy: one of the most innovative treatments for multiple myeloma. T lymphocytes are collected from the patient’s blood and genetically modified in a specialized laboratory to recognize a specific marker on myeloma cells. Once reinfused into the bloodstream, these modified cells can identify and destroy cancer cells. CAR T-cell therapy is administered as a single infusion and requires hospital admission to monitor and manage potential side effects associated with immune activation.

Biologic agents are drugs that interfere with specific cellular pathways involved in the growth and survival of myeloma cells, leading to their destruction.

These therapies include:

• Proteasome inhibitors, such as bortezomib and carfilzomib
• Immunomodulatory agents, such as thalidomide, lenalidomide, and pomalidomide

These drugs are commonly used in combination with other therapies as part of the treatment strategy for multiple myeloma.

Chemotherapy uses drugs that destroy cancer cells by targeting their rapid growth and division.

Because chemotherapy interferes with cellular replication, it can also affect some healthy cells in the body, leading to side effects. These effects are generally temporary, tend to resolve after treatment is completed, and can often be effectively managed with modern supportive therapies.

Autologous stem cell transplantation allows the administration of high-dose chemotherapy, with the aim of eliminating as many myeloma cells as possible.

Because high-dose chemotherapy can temporarily damage the bone marrow, previously collected stem cells are reinfused after treatment. This enables the bone marrow to recover more rapidly and restore the production of red blood cells, white blood cells, and platelets.

This procedure is performed during a hospital admission, which typically lasts approximately three weeks.

Radiotherapy is a treatment that uses high-energy radiation to destroy cancer cells.

In multiple myeloma, radiotherapy is used primarily for pain relief, helping to reduce symptoms caused by osteolytic lesions or localized collections of tumor plasma cells.

Radiotherapy may also be used with curative intent, typically at higher doses, in the treatment of solitary plasmacytoma.

Patients with newly diagnosed multiple myeloma may receive treatment with zoledronic acid, administered as a monthly intravenous infusion, typically for at least one year and up to two years after the start of therapy.

This treatment helps strengthen bones affected by osteolytic lesions and reduces the risk of pathological fractures.

Before starting zoledronic acid, patients should undergo an assessment of kidney function and a dental evaluation to identify any untreated dental disease or active oral infections.

These conditions may increase the risk of osteonecrosis of the jaw, a rare but important side effect associated with bisphosphonate therapy.

Treatment for patients eligible for autologous stem cell transplantation consists of several phases and combines different therapies to achieve the maximum possible reduction of myeloma cells.

Induction Therapy

The first phase, known as induction therapy, involves the administration of three or four biologic and immunotherapeutic agents with the aim of rapidly reducing the tumor burden.

When clinically appropriate, treatment can be delivered in a day hospital setting, with medications administered subcutaneously or intravenously by nursing staff, while oral therapies are taken at home.

One of the most commonly used induction regimens combines daratumumab, bortezomib, thalidomide, and corticosteroids, administered over four 28-day cycles.

Stem Cell Collection

Following induction therapy, hematopoietic stem cells are collected from the patient. These cells are the precursors of all blood cell types and are harvested through a procedure called stem cell apheresis.

Stem cell collection is a non-invasive procedure, similar to an extended blood donation, and can be performed on an outpatient basis or during a short hospital stay.

Autologous Stem Cell Transplantation

After stem cell collection, patients are admitted to hospital for autologous stem cell transplantation.

During hospitalization, high-dose chemotherapy with melphalan is administered to eliminate any remaining myeloma cells. The previously collected stem cells are then reinfused through a procedure similar to a blood transfusion, allowing the bone marrow to recover more rapidly and restore the production of red blood cells, white blood cells, and platelets.

Consolidation and Maintenance Therapy

Following recovery from transplantation, patients may receive two cycles of consolidation therapy, using regimens similar to those administered during induction, to further strengthen the treatment response.

This is followed by maintenance therapy, usually consisting of an oral non-chemotherapy biologic agent taken at home, with the aim of prolonging disease remission.

During this phase, patients undergo regular follow-up visits, initially at shorter intervals and then progressively less frequently, to monitor both disease status and overall clinical condition.

Patients who are not eligible for autologous stem cell transplantation are typically treated with combinations of two or three immunotherapy and biologic agents, administered on an outpatient basis by specialized nursing staff.

The choice of treatment is not based on age alone. Other important factors are carefully evaluated, including the presence of comorbidities, the patient’s functional status and level of independence, and the availability of caregiver support.

All treatment options are discussed with the patient, taking into account their individual preferences, needs, and treatment goals, to ensure a personalized and shared decision-making process.

Multiple myeloma is often managed as a chronic disease, characterized by periods of remission alternating with phases of relapse that may require additional treatment.

Fortunately, several effective therapeutic options are available for patients with relapsed disease. Treatment generally consists of combinations of immunotherapies and biologic agents, often different from those used at the time of diagnosis, in order to target myeloma cells through different biological mechanisms.

Chemotherapy plays a more limited role in the treatment of relapsed multiple myeloma and is used less frequently than in the past, as newer targeted and immunotherapeutic approaches have become available.

In some patients, tumor plasma cells are present without the typical signs or symptoms of multiple myeloma.

This condition is known as asymptomatic or smoldering multiple myeloma and does not require immediate treatment. Instead, patients undergo regular monitoring, including assessment of the monoclonal component, laboratory tests every 3 to 6 months, and MRI examinations, usually at least once a year.

Smoldering multiple myeloma carries a risk of progression to symptomatic multiple myeloma. The level of risk depends on several clinical and biological factors, which are used to determine the frequency of follow-up evaluations.

The aim of monitoring is to detect disease progression at an early stage, before significant organ damage or other complications develop.

It is important to note that some patients with smoldering multiple myeloma may never develop symptoms and can continue with observation alone, with follow-up intervals gradually extended over time.

The treatment of choice for solitary plasmacytoma is radiotherapy.

Radiotherapy is typically delivered in daily sessions, Monday through Friday, over several weeks, depending on the prescribed radiation dose. Each treatment session generally lasts only a few minutes.

The goal of radiotherapy is to achieve local disease control and, in many cases, long-term remission.

Many of the drugs used to treat amyloidosis are the same as those employed in the treatment of multiple myeloma.

The type, dose, and intensity of therapy are carefully tailored according to the organs affected by amyloid deposits and the patient’s overall clinical condition.

Management of amyloidosis requires a multidisciplinary approach and may involve specialists from different fields, including nephrology, cardiology, and gastroenterology, depending on the sites of organ involvement.

Treatment for multiple myeloma may be associated with side effects that can affect quality of life to varying degrees. However, many of these effects can be managed effectively and, in some cases, prevented through appropriate supportive treatments and lifestyle measures.

At the Candiolo Cancer Institute, physicians and nurses within the GIC provide continuous support to help patients manage any side effects that may arise during treatment. The goal is to ensure that each patient receives comprehensive care throughout every stage of the therapeutic pathway.

To ensure timely support and provide prompt answers to questions or concerns, the Candiolo Cancer Institute offers a dedicated assistance service for all patients.

From Monday through Friday, between 8:00 a.m. and 5:00 p.m., patients can contact the Oncology Day Hospital Secretariat at +39 011 993 3775 to request an urgent consultation.

Patients are promptly connected with their specialist physician, ensuring rapid access to expert advice, clear information, and immediate support when needed.

Cancer patients often have complex needs that extend beyond the treatment of the disease itself and require comprehensive, multidisciplinary care.

At the Candiolo Cancer Institute, patients who need additional support have access to specialists from a range of disciplines, ensuring personalized management of cancer-related symptoms and associated conditions. Services may include nutritional counseling, physical rehabilitation, pain management, and support for other medical needs that may arise during the course of treatment and recovery.

The goal is to improve quality of life, promote overall well-being, and provide comprehensive care tailored to each patient’s individual needs.

The Social Work Service at the Candiolo Cancer Institute provides information, guidance, and support to patients and their families regarding access to community services and the welfare and social security benefits available under current legislation.

During dedicated consultations, social workers assist with matters such as disability recognition, access to aids and prosthetic devices, employment-related benefits and leave, and other social support services.

The service is available on Wednesdays and Fridays from 9:00 a.m. to 1:00 p.m. and can be contacted at +39 011 993 3059.

Response to treatment is primarily assessed by measuring the monoclonal component in blood and/or urine, typically at every treatment cycle or every 2 to 3 cycles. When treatment is effective, the monoclonal component progressively decreases and may eventually become undetectable.

When the monoclonal component disappears or is reduced by more than 90%, the physician may request a repeat bone marrow aspiration to evaluate the reduction, or in the best cases, the disappearance of tumor plasma cells from the bone marrow. Although this assessment is not routinely required in clinical practice, it can provide valuable information regarding minimal residual disease and prognosis.

Treatment response is also monitored through imaging studies, usually using the same technique performed at diagnosis, such as:

• Whole-body low-dose CT
• PET-CT
• MRI

The timing of these examinations is determined by the physician according to the patient’s clinical situation and treatment course.

Most therapies for multiple myeloma are administered on a continuous basis and are maintained until disease progression or the development of unacceptable treatment-related toxicity.

In the event of disease relapse, which is often identified by an increase in the monoclonal component with or without the recurrence of symptoms, the physician may request a new bone marrow biopsy and aspiration to reassess the burden of tumor plasma cells and evaluate bone marrow function.

Additional imaging studies may also be performed to identify any new osteolytic lesions or other signs of disease progression.

Thanks to the large number of cases treated each year, the Candiolo Cancer Institute is a national reference center for the care of this disease. This extensive experience allows us to manage even the most complex cases, always using a personalized approach, tailored to the clinical and individual profile of each patient.

Establishing a treatment plan always begins with an accurate and timely diagnosis. Patients have access to state-of-the-art imaging technologies, such as ultrasound, contrast-enhanced CT, MRI, and cholangio-RM, which are critical for accurately assessing the extent of the tumor.

Advanced laboratory tests, including molecular analyses, are also available to help define biological features of the disease and guide treatment choices.

As an IRCCS (Scientific Institute for Research, Hospitalization, and Healthcare), the Candiolo Cancer Institute combines clinical care with a strong focus on scientific research. Patients can be considered for participation in active clinical trials, offering access to innovative therapies not yet available in standard practice. This integration of care and research is a distinctive strength that translates into tangible benefits for patients.

The Interdisciplinary Care Group (GIC or MDT) supports the patient at every stage: from diagnosis, through treatment, to follow-up. Special attention is paid to nutritional support, psychological health and reintegration into daily life. The organization of checkups, examinations, and treatment is designed to ensure continuity, serenity, and a humane, caring approach to each patient’s needs.