Multiple Myeloma /Amyloidosis Service
What is Multiple Myeloma?
Multiple Myeloma is a cancer of the blood and bone marrow arising from a type of white blood cell called a plasma cell. Multiple myeloma, sometimes referred to as MM, or simply as myeloma, affects about 26,850 Americans each year.
Plasma cells normally reside in the bone marrow where they make proteins (antibodies or immunoglobulins) that help the immune system fight infection.
When plasma cells grow out of control and become cancerous, they are called myeloma cells. As these cancer cells increase, they crowd the bone marrow so it can no longer produce enough healthy cells. As the number of oxygen-carrying red blood cells decline, patients may develop anemia, appearing pale, tired or short of breath. A decline in platelets that normally help the blood clot may lead to easy bruising or bleeding. A decline in white blood cells puts patients at increased risk for infections that can be life-threatening.
Myeloma cells also produce abnormal proteins (monoclonal or M-proteins) that make the kidneys to work harder to filter the blood, thus leading to kidney damage.
Myeloma cells affect the cells that keep bones healthy. Bones are constantly being broken down and rebuilt, a process that ensures they remain strong. In myeloma, a signal is sent to the osteoclasts, cells that break the bones down, but there is no corresponding message sent to the osteoblasts, the cells that rebuild the bones. Further myeloma cells can also form a mass weakening the surrounding bone structure leading to an increased risk of fracture. As the bones degenerate, calcium is also released into the blood causing symptoms such as fatigue, constipation and confusion.
When myeloma cells grow in just one area of the bones or soft tissues they may form a tumor known as a solitary plasmacytoma. If no other evidence of disease is found beyond this isolated tumor, the patient is often treated with local therapy such as radiation.
The Multiple Myeloma Center at Columbia University provides the most comprehensive care for patients with this disease, collaborating with physicians from a variety of disciplines. As leaders in translational research, our physicians offer patients the opportunity to participate in clinical trials offered only at Columbia and a few select medical centers, providing access to the most promising new therapies.
What are the risk factors for MM?
- Age. MM is most common in patients over 60 with only 2 percent of cases occurring in those under 40. The average age for diagnosis is 70.
- Race. MM is twice as prevalent in African Americans.
- Family history. If a sibling or parent has had MM, an individual’s chance of being diagnosed with this disease is four times higher than average. However, most MM patients have no affected relatives.
- Previous conditions. Patients diagnosed with a solitary plasmacytoma have a higher risk of developing MM.
- Gender. MM is slightly more common in men.
- Radiation exposure. High levels of radiation such as those found at malfunctioning nuclear power plants may increase a patient’s risk of developing MM.
- Monoclonal gammopathy of unknown significance (MGUS). Patients with a monoclonal (M) protein in their blood but no other evidence of myeloma are diagnosed with MGUS. These patients have a slightly increased chance (1 percent per year) of developing MM and need a lifelong follow up.
What are the symptoms of MM?
As myeloma cells increase, the bones begin to degenerate, releasing calcium into the bloodstream. This condition, known as hypercalcemia, can affect the heart, kidneys, gastrointestinal tract and brain but it is often reversible if caught early enough. The symptoms of hypercalcemia include:
- Frequent urination
- Frequent thirst
- Muscle weakness
- Drowsiness or confusion
- Kidney failure
Other symptoms related to MM are
- Bone pain
- Weight loss
- Repeated infections
- Weakness or numbness in the legs
- Back pain
- Rib pain
- Broken bones, usually in the spine
- Spinal Cord Compression
Some people with MM may not have any symptoms. In these cases, myeloma protein is found in the blood or urine when tests are done for other purposes.
How is MM diagnosed?
A physician will perform a complete physical examination, then order the following diagnostic procedures if myeloma is suspected:
- X-rays and /or Computer Tomography of the bones
- Blood and urine tests
- Magnetic Resonance Imaging (MRI). Using a combination of large magnets and radiofrequencies, a computer will produce detailed images of organs and structures within the body.
- Bone marrow aspiration and/or tissue biopsy. A physician will take a small amount of bone marrow fluid (aspiration) and/or solid bone marrow tissue (a core biopsy), then examine the sample looking at the number, size, and maturity of blood cells and/or abnormal cells. A bone marrow biopsy is performed by numbing the area—usually the back of the hip—and then inserting a needle into the bone to extract the marrow cells.
How is MM treated?
Specific treatment for myeloma is based on:
- The patient’s age, overall health, and medical history
- The extent of the disease
- The patient’s tolerance for specific medications, procedures, or therapies
- Expectations for the course of the disease
- The patient’s opinion or preference
Treatment may include medications to control pain and care of fractures, as well as
- Immune modifying drugs
- Proteosome Inhibitors
- Monocional Antibodies
- Radiation Therapy
- Stem cell transplantation
These drugs help the body’s immune system fight the cancerous myeloma cells. Our experts use the following approved drugs in this class:
- Lenalidomide (Revlimid) is similar to thalidomide but with fewer side effects and appears to work better for patients with MM..
- Pomalidomide (Pomalyst) is the newest immune –modifying drug approved for MM, is often used when other drugs are no longer effective.
Proteasomes break down proteins in the cells that are damaged or no longer needed. Proteasome inhibitors block this process and the result is cell death. Cancerous cells are more sensitive to this blockade than healthy cells, and are apt to die sooner, when subjected to these drugs.
- Bortezomib (Velcade) is first generation proteasome inhibitor approved for MM.
- Carfilzomib (Kyprolis) is the second generation proteasome inhibitor approved for MM and can be effective when other drugs such as bortezomib no longer work.
Daratumumab is a human monocional antibody that binds with the CD38 molecule, which is highly expressed on the surface of MM cells. daratumumab is approved for pateints who have recieved at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomolulatory agent.
Steroids such as prednisone and dexamethasone have been the cornerstone of treatment of MM for many years and are often given in combination with other therapies.
Chemotherapy drugs enter the blood stream with the purpose of destroying cancer cells. These drugs can be taken by mouth or given in a vein or a muscle. Many different types of drugs are used to treat multiple myeloma and chemotherapy drugs are often used in combination to increase their effectiveness, since MM often spreads throughout the body. The chemotherapy agents used to treat MM may include
- Cyclophosphamide (Cytoxan)
- Bendamustine (Trenda)
Combinations of these drugs are more effective than any single drug. Often chemotherapy agents are combined with other types of drugs like proteasome inhibitors, Immune-modifying drugs and corticosteroids.
Radiation therapy is given if myeloma weakens the vertebrae or backbones, resulting in risk that these bones collapse and start pressing on the nerves and spinal cord. Immediate treatment with radiation therapy may prevent paralysis.
Radiation Oncologists may use high-energy x-rays to destroy cancer cells and treat areas of bone damaged by myeloma. In External Beam Radiation Therapy, the energy source is aimed at the body by a machine. This treatment may be given over several weeks.
Stem Cell Transplantation
- Autologous Stem Cell Transplant
- Allogenic Stem Cell Transplant
Our Expert Team
- Suzanne Lentzsch, MD, PhD, Associate Professor of Medicine at CUMC; Director, Myeloma and Amyloidosis Service
- Markus Y. Mapara, MD, PhD, Professor of Medicine at CUMC ; Director, Blood and Marrow Transplantation Program
- Shahzad Raza, MD, FACP Assistant Professor of Medicine at CUMC
- Ran Reshef, MD, PhD Assistant Professor of Medicine at CUMC
- Research Scientists
- Shirong Li, PhD
- Jing Fu, PhD
Clinical Trials and Research
The Multiple Myeloma Center at Columbia University specializes in providing novel therapies through clinical trials. We are able to translate our laboratory discoveries into our clinical practice very quickly, and conduct an active program of basic and clinical research aiming at improving patient outcomes.
At Columbia, patients have access to novel drugs and may participate in our own investigator-initiated trials as well as multi-center trials offered at major medical centers, nationally and internationally.
- The Multiple Myeloma Research Foundation
- The International Multiple Myeloma Research Foundation
- Leukemia & Lympoma Society
Columbia Amyloidosis Multidisciplinary Program (CAMP)
The Columbia Amyloidosis Multidisciplinary Program (CAMP) under the leadership of Dr Suzanne Lentzsch is an international and national referral center for the diagnosis and treatment of amyloidosis, offering a comprehensive multi-disciplinary approach to diagnosis and treatment of this multi-organ disorder. This unique program was established in order to fill a significant void in the diagnosis and treatment of systemic amyloidosis, with a view to acquiring a better understanding of the causes of amyloidosis and improving care for patients who have the disease. Each year the Columbia Amyloidosis Multidisciplinary Program cares for more than hundred patients with this rare and challenging disease.
Physician of Columbia University have long been leaders in amyloidosis research. In 1974, Takashi Isobe, MD, and Elliott Osserman, MD, from the Department of Medicine and the Institute of Cancer Research at Columbia conducted a landmark study published in The New England Journal of Medicine on amyloid-related immunoglobulins (a Y-shaped protein that makes antibodies) and Bence-Jones proteins that infiltrate normal tissue resulting in amyloid formation. This research set the stage for the current multidisciplinary approach to amyloidosis at Columbia University.
Amyloidosis specialists in hematology-oncology, cardiology, nephrology, neurology, bone marrow transplantation, heart pathology and kidney pathology participate in patient evaluation and care with the goal to induce remissions of the disease, manage symptoms, limit the production of further amyloid proteins, and support the affected organs. In regularly multi-disciplinary meetings we discuss each patient in depth, considering how to best manage a range of symptoms and how to customize treatment plans for every patient. We identify a tailored approach based on how many organs are affected, the physiologic age of the patient, and his or her activity level. This ensures a high level quality multidisciplinary approach.
So far all therapies in amyloidosis solely focus on the destruction of plasma cells and subsequently the stop of the production of light chains forming the amyloid. Hence new accumulation of amyloid will be prohibited but unfortunately existing amyloid will not be affected by the treatment resulting in continuous impairment of the organ function. Monoclonal antibodies targeting directly the amyloid fibrils and subsequently destroying the existing amyloid is a very new and exciting approach. Therefore our center focuses on the use of such monoclonal antibodies. CUMC is the only center worldwide that offers treatment with the monoclonal antibody 11-1F4 that was developed by Dr Alan Solomon at the University of Tennessee. We hope that with the use of the excisting and inivative approach we will be able to destroy the existing amyloid and subsequently improve the organ function.
Our Columbia Amyloidosis Multidisciplinary Program (CAMP) is known for providing
- A comprehensive and multidisciplinary team approach to amyloidosis involving hematologists, nephrologist, neurologists, cardiologists, pathologists, clinical and basic research experts.
- Personalized therapy based on the type of amyloidosis, patient’s organ involvement and the age of each patient
We also provide patient support:
- Nurse Navigators to guide patients through every step of diagnosis and treatment
- Dedicated research nurses caring for patients in clinical trials
- Medical advice on lifestyle, exercise, diet and nutrition
- Psychological counseling and support groups
- Consultation on pain management
- Patient web portals offering easy access to test results, appointments, follow-up care
Other services and opportunities available through CAMP include:
- Mass Spectrometry and Genetic Testing. We are using mass spectrometry to pinpoint the type of amyloidosis. This is critical in order to choose the correct treatment. Further by genetic testing will rule out or confirm a hereditary (familial) type of amyloidosis.
- Opportunities to participate in clinical trials. We offer a wide range of trials, many of them initiated by our physicians and offering access to latest drug developments and the most advanced and innovative treatments. Further, Dr Suzanne Lentzsch leads and initiated a multicenter trial within the Amyloidosis Network including five centers in the U.S testing the role of Bendamustin in AL Amyloidosis.
- Access to anti-amyloid antibody trials. We offer clinical trials using antibodies directly targeting the amyloid deposits for newly diagnosed (NEO001) as well for relapsed refractory amyloidosis (11-1F4)
What is amyloidosis?
Amyloidosis is a rare disease affecting about 3000 patients in the United States each year. Although Amyloidosis may be associated with blood cancers such as multiple myeloma (link) it is not a cancer itself. Amyloidosis results from the buildup of an abnormal protein call amyloid. The amyloid protein accumulates in tissues and organs. This accumulation of the amyloid protein can cause symptoms and organ damage affecting how the heart, kidneys, liver, spleen, nervous system and gastrointestinal tract work.
The severity of amyloidosis largely depends on which organs are affected and how much amyloid has accumulated. The most life-threatening cases occur in patients with amyloid deposits in the heart.
Amyloidosis can be difficult to diagnose because its symptoms often mimic those of other conditions. Although it is a very uncommon, it is likely under-diagnosed. Patients often visit many doctors before finding the cause of their illness. Physicians at the Herbert Irving Cancer Center place a high priority on diagnosing and treating patients in the early stage of the disease before organs are seriously affected.
What are the different types of amyloidosis?
- Amyloidosis is classified into four major types:
- Primary amyloidosis (AL) is the most common form and results from the abnormal production of light chain proteins, which are a part of antibodies. These light chains are produced by blood cells called plasma cells. The light chains can be also increased in multiple myeloma but they do not usually accumulate in tissues as in amyloidosis.
- Secondary (AA) amyloidosis results from the accumulation of serum amyloid protein A as a complication of chronic inflammatory such as Familial Mediterranean Fever (FMF) or rheumatoid arthritis.
- Familial amyloidosis occurs due to genetic mutations in proteins that lead to formation of amyloid fibrils. This type of amyloidosis is inherited. The most common form of familial amyloidosis is caused by a mutation in the transthyretin protein (ATTR).
- Senile amyloidosis, also called “wild type” amyloidosis is caused by an accumulation of normal unmutatet transthyretin protein that occurs with aging and especially affects the heart. As the population ages, experts note that TTR cardiac amyloidosis has become more commonplace.
Another form of amyloidosis is called Localized amyloidosis, which is an accumulation that occurs in areas such as the larynx or the skin and usually does not need systemic therapy.
What are the risk factors for developing amyloidosis?
- Certain risk factors may predispose patients to primary amyloidosis, including older age and a previous diagnosis of another blood disease called MGUS or multiple myeloma.
- Patients with a chronic infectious or inflammatory disease may be at greater risk of developing secondary amyloidosis.
- Patients with a family history of this condition are at greatest risk of developing familial amyloidosis.
What are the symptoms of amyloidosis?
Amyloidosis symptoms vary depending on the organ that is affected and how much protein has built up in that area. Since one or several organs may be affected symptoms may vary widely, and seem vague or general, at first. Often it takes a team of specialists to diagnose this illness. Since this is a rapidly progressing disease, time is of the essence—it is important to begin treatment as soon as possible.
- When the kidneys are affected, patients may report foamy urine. A physician will order a urine test to find out if amyloid protein that has accumulated in the urine.
When the nervous system is affected, patients may develop numbness, tingling or weakness in the arms or legs. Carpal tunnel syndrome may also occur. Very often patients experience a change or loss of taste as well as low blood pressure and dizziness when changing the positions.
- When there is abnormal accumulation of amyloid protein in the heart, patients may experience shortness of breath, dizziness, irregular heartbeat or edema—swelling of the ankles and legs.
- If amyloid has accumulated in the gastrointestinal system patients may have heartburn (Gastrointestinal reflux disease GERD), difficulty swallowing, bleeding, diarrhea, constipation and, a hallmark symptom is swelling of the tongue (macroglosia)
- Other symptoms may also include unexplained weight loss, severe fatigue, skin thickening or easy bruising, purpura—purple patches around the eyes.
How is amyloidosis diagnosed?
To diagnosis this complex disease, doctors typically begin with a physical exam, followed by blood and urine tests. If abnormal proteins are detected in the blood or urine, the next step is a tissue biopsy. Pathologists evaluate these tissue samples with special staining, and mass spectrometry analysis.
Usually biopsies are conducted in an outpatient setting.
Samples may be taken from the patient’s abdominal fat, or bone marrow. The abdominal fat pad biopsy involves numbing the skin and the fat underneath with a numbing medicine. A needle is then inserted throught the skin and into the fat pad underneath. A small piece of fat is removed with the needle. The tissue sample is then examined by a pathologist for abnormal plasma cells or amyloid deposits.
Occasionally, a biopsy may need to be taken from the heart, liver or kidney to help pinpoint the specific organ affected. For example, if a patient has heart failure then a cardiologist would biopsy the heart, or if a patient has renal failure then a nephrologist would biopsy the kidney.
Because amyloidosis can affect so many different organs, it is critical to have a multidisciplinary team with specialized experience in all of the different organ systems. At Columbia, we bring together experts in many different fields to consult with the patient, during a single appointment, thereby minimizing the number of hospital visits needed.
How is amyloidosis treated?
Because amyloidosis can affect so many organs in the body at once, Columbia University Medical Center has assembled a team of specialists in hematology-oncology (doctors who specialize in blood disorders), cardiology (doctor who treats heart conditions), nephrology (doctors who treat kidney problems), pathology (doctors who diagnose diseases by reviewing laboratory tests and examining tissue biopsies), neurology (focuses on issues involving the nerves), and bone marrow transplantation to collaborate and provide the highest level of patient care. Our goal is to help manage symptoms, limit the production of further amyloid proteins, and support the affected organs.
Because a tailored approach is based on many factors, including how many organs are affected, the physiologic age of the patient, and his or her activity level, our multidisciplinary team discusses each case in depth, considering how to best manage a range of symptoms and how to customize treatment plans for every patient. When untreated, there is a poor prognosis for amyloidosis. Therefore, doctors of our team place a high priority on intervening early before multiple organs are seriously affected.
While no existing therapy appears to reverse the buildup of amyloid proteins in tissues or organs, studies on the combination of melphalan, bortezomib, and dexamethasone are promising and have shown that this regimen may help the organs affected by amyloidosis function better.
Treatments for amyloidosis include:
- Proteasome Inhibitors
- Therapeutic Drugs
- Blood Stem Cell Transplant
- Surgery: Heart Transplant, Kidney Transplant, Liver Transplant
Primary amyloidosis (AL) is usually treated with a chemotherapy-based regimen (similar to that used for multiple myeloma) to destroy the abnormal plasma cells that give rise to the amyloid proteins or plaque. Chemotherapy drugs used to treat amyloidosis include melphalan (Alkeran) and cyclophosphamide (Cytoxan, Neosar) combined with dexamethasone (multiple brand names) and prednisone (multiple brand names).
All established therapies in amyloidosis focus on the destruction of plasma cells and subsequently the stop of the production of light chains forming the amyloid. Hence new accumulation of amyloid will be prohibited but unfortunately existing amyloid will not be affected by the treatment resulting in continuous impairment of the organ function. Monoclonal antibodies targeting directly the amyloid fibrills and subsequently destroying the existing amyloid is a very new and exciting approach. Therefore our center focuses on the use of such monoclonal antibodies. CUMC is the only center worldwide that offers treatment with the monoclonal antibody 11-1F4 that was developed by Dr Alan Solomon at the University of Tennessee.
A new class of drugs called proteasome inhibitors may also be used in different combinations with chemotherapy drugs. These drugs affect the cell structure that regulates proteins involved in cell replication and survival. They essentially block the function of proteins that allow the myeloma cells to grow.
Stem Cell Transplantation
Around 20% of patients with amyloidosis and an appropriate organ function are eligible for stem cell transplantation. If a patient with amyloidosis is in good condition (with fewer than three organs affected, with adequate cardiac function, and laboratory results), a bone marrow transplant specialist can perform the transplant. If the patient has more advanced disease, our team will pretreat the patient with a chemotherapy regimen to decrease the production of the amyloid plaque, and then perform the stem cell transplant once the patient is in a better performance status. Bone marrow transplant specialists at have found this procedure to be very promising. More information on Stem Cell Transplantation can be found here: http://www.cumc.columbia.edu/hematology-oncology/patient_care/blood-bone-marrow-transplantation.
Treatment of Heart Amyloidosis
Accumulation of amyloid protein in the heart reduces the ability of the heart to fill and can also result in damage to the heart’s electrical system. If left untreated, cardiac amyloidosis can lead to heart failure. Therefore, doctors at CUMC place a high priority on intervening early before this organ is affected.
If our cardiologists suspect amyloidosis after an electrocardiogram and echocardiogram, a definitive diagnosis can be made with a biopsy of the heart. The procedure is safe if performed at an experienced institution. Our physicians have significant expertise in endomyocardial biopsy. They routinely perform more than 20 heart biopsies each week at one of the largest heart failure and transplant program in the country.
Recently, our doctors have been successfully employing cardiac magnetic resonance imaging (MRI)—a less invasive method—to accurately diagnose cardiac amyloidosis.
Unfortunately amyloidosis can progress to the point where a heart transplant or a mechanical assist device is required. Founded over a quarter of a century ago, the heart transplant program at NewYork-Presbyterian Hospital/Columbia University Medical Center has long been the top cardiac transplant program in the US and a leader in the development and implantation of mechanical assist devices, also called VADs (Ventricular Assist Devices). These pumps can be used to support heart function and blood flow in people who have weakened hearts.
Kidney amyloidosis inhibits the kidneys from properly removing waste from the body, and if left untreated can lead to kidney failure. Therefore, doctors at CUMC place a high priority on intervening early before the kidney is seriously affected. Our kidney transplantation program are the oldest in the region and the largest in the nation. Learn more about kidney transplantation for amyloidosis.
The amyloid deposits in most cases of familial (hereditary) TTR amyloidosis are composed of the abnormally structured protein transthyretin (TTR), which is made in the liver. In those patients a liver transplant will cure the patients and will stop the production of an abnormal transthyretin protein.
The Center for Liver Disease and Transplantation at NewYork-Presbyterian Hospital is a multidisciplinary program that provides medical treatment, surgery, transplantation, and patient support.
Learn more about liver transplantation.
Clinical Trials and Research
The Herbert Irving Comprehensive Cancer Center is a national leader in research on amyloidosis. The Program’s Director, Suzanne Lentzsch, MD, is the principal investigator of a number of amyloidosis-related clinical trials currently being conducted at Columbia/NewYork-Presbyterian and allowing our patients to benefit from emerging therapies. In addition she is the principle investigator of a multi-center trial in the Amyloidosis Network which includes five major medical centers in the United States. The researchers are studying the causes of systemic amyloidosis and considering ways to improve patient care. Preliminary results are very promising and enrollment is currently open.
Further our center offers clinical trials using a monoclonal antibody NEOD001 and 11-1F4 that are directly targeting the amyloid plaques.
To find a Clinical Trials at the HICCC, please go to https://recruit.cumc.columbia.edu/investigatortrials/425
Amyloidosis Patient Resources
Our Columbia Amyloidosis Multidisciplinary Program Team of Experts
- Suzanne Lentzsch, MD, PhD (Hematology), Associate Professor of Medicine at CUMC; Director, Myeloma and Amyloidosis Service
- Markus Y. Mapara, MD, PhD (Blood Stem Cell Transplant), Professor of Medicine at CUMC ; Director, Blood and Marrow Transplantation Program
- Shahzad Raza, MD, FACP (Hematology), Assistant Professor of Medicine at CUMC
- Ran Reshef, MD, PhD (Blood Stem Cell Transplant), Assistant Professor of Medicine at CUMC
- Thomas H. Brannagan, MD (Neurology)
- Maryjane Farr, MD (Cardiology)
- Matthew S. Maurer, MD (Cardiology)
- Daniel O’Conner, MD (Cardiology)
- Gregg F. Rosner, MD (Cardiology)
- Jai Radhakrishnan, MD (Nephrology)
- Charles C. Marboe, MD (Cariac Pathology)
- Glen Markowitz, MD (Nephro Pathology)
- Research Scientists:
- Shirong Li, PhD
- Jing Fu, PhD
- Katherine Morel-Perez, Administrative Assistant
- Keyra A. Duran, Practice Coordinator
- Lorely Taveras, Patient Service Representative
- Karolina Feldman, Nurse Practitioner
- Elsa Delille, Nurse Practitioner
- Katharina Ganapathi, Clinical Coordinator III
- Kimberly Bair, Clinical Coordinator III
- New Patient Appointments: (212) 305-5098
- Outpatient Clinic: (646) 317-4805
- Administrative Office: (646) 317-4840
- NewYork-Presbyterian Operator: (212) 305-2500