Founded in 1990, the International Myeloma Foundation (IMF) is the first and largest organization focusing specifically on myeloma. The IMF’s reach extends to more than 525,000 members in 140 countries. The IMF is dedicated to improving the quality of life of myeloma patients while working toward prevention and a cure through our four founding principles: Research, Education, Support, and Advocacy.
RESEARCH The IMF is dedicated to finding a cure for myeloma, and we have a range of initiatives to make this happen. The International Myeloma Working Group, which emerged from the IMF’s Scientific Advisory Board established in 1995, is the most prestigious organization with more than 300 myeloma researchers conducting collaborative research to improve outcomes for patients while providing critically appraised consensus guidelines that are followed around the world. Our Black Swan Research Initiative® is bridging the gap from long-term remission to cure. Our annual Brian D. Novis Research Grant Program is supporting the most promising projects by junior and senior investigators. Our Nurse Leadership Board, comprised of nurses from leading myeloma treatment centers, develops recommendations for the nursing care of myeloma patients.
EDUCATION The IMF’s webinars, seminars, and workshops provide up-to-date information presented by leading myeloma scientists and clinicians directly to patients and their families. We have a library of more than 100 publications for patients, care partners, and healthcare professionals. IMF publications are always free-of-charge, and available in English and select other languages.
SUPPORT The IMF InfoLine responds to your myeloma-related questions and concerns via phone and email, providing the most accurate information in a caring and compassionate manner. We also sustain a network of myeloma support groups, training hundreds of dedicated patients, care partners, and nurses who volunteer to lead these groups in their communities.
ADVOCACY We empower thousands of individuals who make a positive impact each year on issues critical to the myeloma community. In the U.S., we lead coalitions to represent the interests of the myeloma community at both federal and state levels. Outside the U.S., the IMF’s Global Myeloma Action Network works to help patients gain access to treatment. Learn more about the ways the IMF is helping to improve the
us at 1.818.487.7455 or 1.800.452.CURE, or visit myeloma.org .
You are not alone
The International Myeloma Foundation (IMF) is here to help you. The IMF is committed to providing information and support for patients with multiple myeloma (which we refer to simply as “myeloma”) and their care partners, friends, and family members.
We achieve this through a broad range of resources available on our website myeloma.org, and through numerous programs and services such as seminars, webinars, workshops, and the IMF InfoLine, which consistently provides the most up-to-date and accurate information about myeloma in a caring and compassionate manner. Contact the IMF InfoLine at 1.818.487.7455 or InfoLine@myeloma.org.
What you will learn from this booklet
Myeloma is a cancer that is not known to most patients at the time of diagnosis. To play an active role in your own medical care and to make good decisions about your care with your doctor, it is important and helpful to learn about myeloma, as well as its treatment options and supportive care measures.
The IMF’s Understanding-series publications address treatments for myeloma, supportive care measures, and the tests that are used to diagnose, monitor, and assess disease status throughout its course.
This booklet is intended for myeloma patients in the United States who are in discussions with their treating doctors about the possibility of having an autologous stem cell transplant (ASCT) as part of their overall treatment strategy. This booklet describes the typical journey of a patient with myeloma in the U.S. who might undergo ASCT, and provides information that may be helpful in decision-making.
If you are newly diagnosed with myeloma, we suggest that you read the IMF’s publication Patient Handbook for the Newly Diagnosed, which will help you to better understand this complex disease.
To learn about myeloma in later disease settings, read the IMF’s publication Concise Review of Relapsed and Refractory Myeloma.
Words in bold+blue type are explained in the “Terms and definitions” section at the end of this booklet. A more comprehensive glossary can be found in the IMF’s publication Understanding Myeloma Vocabulary located online at glossary.myeloma.org.
If you are reading this booklet in electronic format, the light blue links will take you to the corresponding resources. All IMF publications are free-of-charge and can be downloaded or requested in printed format at publications.myeloma.org.
The importance of consulting with an expert
Myeloma is a highly individualized disease. Do NOT compare your myeloma to that of other patients as each case of myeloma is unique and each patient’s myeloma has its own distinct characteristics. This is why it is so important to seek an opinion – or a second opinion – from an experienced myeloma specialist. You may be able to do this in person or your doctor can consult with a myeloma expert remotely.
Please note that medical experts have yet to arrive at a consensus about which myeloma patients will benefit the most from which treatment, including from a successful ASCT. Therefore, general statements regarding patient outcomes both during and after treatment are not appropriate.
It is important to keep in mind that even if you are a good candidate for ASCT – or any other myeloma treatment approach – the ultimate decision is always yours to make.
Rationale for ASCT in myeloma
The overall strategy for a patient with myeloma is to have as many treatment options available as possible, both short-term and long-term, in order to pursue the treatment option most likely to attain a deep and durable response. ASCT is one treatment option to consider for patients with myeloma, and it is the type of transplant used most frequently in myeloma for patients who are eligible.
“High-dose therapy (HDT) with stem cell rescue” is the medical term for ASCT. “Hematopoietic stem cells” is the medical term for the immature cells from which all blood cells develop. Normal stem cells give rise to normal blood components, including red blood cells (RBC), white blood cells (WBC), and platelets. Normal stem cells originate in the bone marrow, the soft and spongy tissue in the center of bones.
In patients with myeloma, the myeloma cells are present in the same bone marrow microenvironment as the normal stem cells. As myeloma cells build up in the bone marrow, they become intermixed with normal stem cells.
Chemotherapy is the use of drugs to kill cancer cells. HDT is more effective at eradicating myeloma cells from the bone marrow than standard-dose chemotherapy. But any treatment that reaches the bone marrow to kill myeloma cells is also capable of damaging your normal stem cells. With reduced bone marrow, your body is less able to produce blood cells that carry oxygen into organs and tissues (RBC), help your blood to clot (platelets), and defend against infection (WBC).
In the ASCT procedure, your peripheral blood stem cells (PBSC) are first collected (“harvested”) from the circulating blood after a mobilizing agent triggers the release of bone marrow stem cells into the bloodstream – this is why ASCT is a “stem cell transplant” and not a “bone marrow transplant.” After HDT has been administered, your own harvested stem cells are reinfused (“transplanted”) into you to “rescue” your bone marrow from the effects of HDT.
Prior to making a decision about ASCT, consider the following key points:
¡ Discuss the benefits and risks of ASCT and other treatment options with your doctor.
¡ ASCT can improve the depth of response and duration (length) of remission, known as progression-free survival (PFS). Transplant doctors usually require at least a 50% reduction in levels of monoclonal protein (myeloma protein, M-protein) as well as other indicators prior to harvesting normal blood stem cells.
¡ While the rates of PFS may be improved with ASCT, the rates of overall survival (OS) are the same with or without transplant.
¡ Myeloma patients who have no minimal residual disease (MRD) after treatment, also called being MRD-negative, have improved OS whether they have undergone ASCT or not. MRD-negativity improves outcomes with or without ASCT.
¡ Quality of life (QoL) and overall costs of treatment favor early ASCT because this produces higher rates of sustained PFS and MRD-negative status.
¡ Discuss with your doctor the option of harvesting your stem cells, then freezing them without undergoing immediate ASCT. If there
is no plan for immediate ASCT, discuss and develop a treatment plan with your doctor.
¡ Ask your doctor to explain the proposed treatment plan for your myeloma.
Please continue reading for a more detailed discussion of ASCT.
Eligibility and decision-making Assessment
In the U.S., eligibility criteria for ASCT varies among institutions. In 2014, the IMF’s International Myeloma Working Group (IMWG) published a consensus statement, which concluded that the arbitrary age of 65 is no longer sufficient to define whether a patient is eligible or ineligible for ASCT. Physiologic age is a more important factor than chronological age, but this does not mean that age is not a factor at all. Your general fitness and any concurrent illnesses will be part of the evaluation to determine appropriate treatment.
In the U.S., there is no upper age limit set in the Medicare National Coverage Determination for ASCT in myeloma, and the Centers for Medicare & Medicaid Services (CMS) have now removed the upper age limit on coverage, leaving the question of eligibility to the patient’s doctor and the Medicare administrative contractor within the patient’s jurisdiction. Visit cms.gov/Medicare/Coverage/DeterminationProcess for more information or speak with your healthcare team.
While ASCT is an option for most myeloma patients upon completion of frontline therapy, not all patients are candidates for this intensive approach. Decisions regarding transplant should be made based on a risk-benefit assessment, as well as the needs and wishes of the patient. You and your doctor must consider all the relevant myeloma-related factors and patient-related factors. The factors to discuss with your doctor include, but are not limited to, the following:
¡ Myeloma-related factors include the stage of disease, its level of aggressiveness, response to prior treatments, beta-2 microglobulin (β2-microglobulin, β2M, or β2M), serum albumin, and chromosomal abnormalities.
¡ Patient-related factors include age, general physical condition, the presence of other medical conditions, and function of the kidneys, heart, lungs, and liver.
¡ Patient preference, as well family and work situations, should be factored into the discussion.
Your doctor will perform a series of tests, and the gathered data will help assess your candidacy for ASCT. Please discuss the following with your doctor before making your decision:
1. Confirm your diagnosis of myeloma and that your myeloma is active and that it requires treatment. If there is any doubt, this is a key moment to seek an opinion from a myeloma expert before moving ahead with a treatment strategy. Discuss with your doctor the treatment strategy optimal for you.
2. After each cycle of induction therapy (usually every 3 to 4 weeks), ask your doctor about your response to treatment. Learn to understand the complete evaluation of the level of response, including bone marrow testing and imaging studies. If your response to therapy is deemed inadequate by your doctor, then other therapy may be recommended before proceeding to ASCT.
3. Ask your doctor if you may run the risk of serious complications.
For information about tests used to monitor and assess myeloma status throughout the disease course, read the IMF’s publication Understanding Your Test Results.
Timing
ASCT may be performed as part of a frontline therapy regimen or at the time of myeloma relapse. When to perform ASCT is an important decision. Most transplant doctors believe that it is better to perform ASCT early in the disease course. However, there is also evidence that if a patient has a deep response to induction therapy, stem cells can be collected and frozen, but the ASCT can be delayed until relapse. Discuss your optimal timing for an ASCT with your doctor.
Chemotherapy
If your doctor considers ASCT to be an option for you, then your initial therapy should be with drugs that don’t damage your normal stem cells prior to harvesting. For example, therapy with Revlimid® (lenalidomide) for more than 4 cycles may impair stem cell collection.
It is also important to note that the use of alkylating agents should be avoided because they can lead to damage of normal stem cells. Alkylating agents are chemotherapy drugs that cross-link the DNA of myeloma cells and block cell division. Alkylating agents were the earliest effective drugs used in the treatment of myeloma.
Preparing for the experience of ASCT
You should feel comfortable and reassured before you begin your ASCT process. You can do a lot to get ready for your ASCT. The IMF has a library of publications about the therapies used for the treatment of myeloma at every stage of the disease. All are free-of-charge and can be downloaded or requested in printed form at publications.myeloma.org.
Be empowered to ask your doctor any questions you may have. Some transplant centers may even pair you up with a fellow patient who has been through the ASCT process and can share a firsthand account of their experience. If possible, bring a friend or a family member to your doctor appointments so that they can help take notes. If available, ask your doctor to provide an “after-visit summary.”
Share what you learn with your loved ones so that they know what to expect – and how they can best help in the weeks and months ahead.
Your transplant center and team
Ask your doctor whether you will receive treatment on an inpatient or outpatient basis. Visit the transplant center and see the rooms where the ASCT procedure and recuperation would take place. If the transplant center location is far from your home, visit the accommodations where you will stay. Many transplant centers have accommodations nearby or can help you find suitable accommodations.
Ask to meet your myeloma transplant team in advance – the doctors, nurses, social workers, psychologists, and allied healthcare professionals. This will help you know who’s who, as well as what resources are available to you and your care partners. ASCT is a complicated medical procedure and you want your transplant team to have both experience and expertise.
Support resources
Having a support network is very important. ASCT can place overwhelming stresses on patients and their loved ones before, during, and after the
procedure. Physical, psychological, emotional, and financial stresses may trigger feelings of anxiety, depression, or anger. We urge you to take advantage of the support resources offered through your hospital, the IMF’s InfoLine and support groups, and through other patient-centric organizations. Ask your doctor about the benefits of psychological counseling or psychiatric consultation.
The process of ASCT in myeloma Induction therapy
Myeloma patients have many options for induction therapy prior to ASCT, including the following:
¡ Darzalex® (daratumumab) + Velcade + Revlimid + dexamethasone [D-VRd] is not formally approved by the FDA, but it is included by the National Comprehensive Cancer Network (NCCN) in its guidelines for the management of myeloma. The primary results of the PERSEUS phase III clinical trial of D-VRd in newly diagnosed multiple myeloma (NDMM) patients eligible for ASCT demonstrate that D-VRd (with SQ administration of Darzalex Faspro) significantly improved PFS and increased depth of response (DpR) with consistent and clinically meaningful PFS benefit across clinically relevant subgroups. The data support the use of D-VRd followed by maintenance therapy with Darzalex + Revlimid [D-R] as a new standard-of-care for ASCT-eligible NDMM when compared to VRd alone followed by maintenance therapy with Revlimid.
¡ Velcade® (bortezomib) + Revlimid + dexamethasone [VRd] may be the most common regimen used, and it was studied in the two largest transplant studies, the IFM and DETERMINATION clinical trials.
¡ Kyprolis® (carfilzomib) + Revlimid + dexamethasone [KRd] has been used and studied before and after ASCT. The FORTE clinical trial demonstrated high efficacy with a favorable safety profile of KRd + ASCT in newly diagnosed myeloma patients.
¡ Darzalex + KRd [D-KRd] is a four-drug combination being used more frequently now. Clinical data has shown that the D-KRd induction regimen is both safe and yields deep responses prior to ASCT, and can lead to a high rate of MRD-negativity in newly diagnosed myeloma patients after ASCT.
In addition, these are the other options listed by the NCCN:
¡ Revlimid + dexamethasone [Rd],
¡ Velcade + cyclophosphamide + dexamethasone [VCd or CyBorD],
¡ Velcade + Adriamycin® (doxorubicin) + dexamethasone [PAd],
¡ Ninlaro® (ixazomib) + Revlimid + dexamethasone [IRd].
The NCCN also lists the following options as useful in certain circumstances:
¡ Velcade + dexamethasone [Vd],
¡ Velcade + thalidomide + dexamethasone [VTd],
¡ Darzalex + VTd [D-VTd],
¡ VTd + cisplatin + doxorubicin + cyclophosphamide + etoposide [VTd-PACE].
Generally, depth of response after induction therapy has been thought to influence the depth of response after ASCT. However, even lesser degrees of response to induction may be sufficient for effective stem cell collection.
Stem cell collection before HDT
To circumvent potential damage of normal blood stem cells in the bone marrow, the stem cells are harvested before you receive chemotherapy with an alkylating agent. This is done through a process called apheresis. A thin flexible catheter is inserted through the skin and into a vein, and blood from the patient is passed through a special machine to remove the stem cells. The rest of the blood is immediately returned to the patient. Apheresis is usually done as an outpatient procedure for 1 to 5 days, lasting from 3 to 4 hours each day.
One of the following protocols may be used prior to harvesting your stem cells:
¡ Protocol 1: The patient receives subcutaneous (SQ) injections with a colony-stimulating factor (CSF) to mobilize the release of stem cells from the bone marrow into the bloodstream. The daily injections are followed by the daily harvesting of stem cells until a sufficient quantity is obtained. Typically, the aim is to harvest enough stem cells for two transplants. The amount of stem cells reinfused into the patient has an impact on the recovery of the patient’s blood cell counts.
¡ Protocol 2: The patient receives both CSF and chemotherapy. Ask your doctor to explain the potential benefits and side effects of using chemotherapy in addition to growth factors. The most commonly used drug to enhance the release of stem cells from the bone marrow into the bloodstream is cyclophosphamide, but there are other drugs that can be used instead. An advantage of cyclophosphamide is that it is also used to treat myeloma, although it usually requires hospitalization while stem cell production is being stimulated. A disadvantage of cyclophosphamide is that it lowers WBC counts and infection might result, possibly requiring another hospitalization. After chemotherapy is completed, a WBC growth factor is given daily by injection for approximately 10 days, then the stem cells are harvested over 2 to 5 days, while the patient is still receiving growth factor injections.
¡ Protocol 3: The patient receives CSF plus a mobilizing agent. In 2008, the FDA approved Mozobil® (plerixafor) for stem cell mobilization in combination with a growth factor. Treatment with growth factors lasts 4 days, then Mozobil is injected under the skin approximately 11 hours before stem cell collection begins. Mozobil is particularly helpful for patients who have difficulty generating enough stem cells for harvesting. There is also the likelihood of fewer apheresis procedures, with reduced number of days on the apheresis machine. In September 2023, the FDA approved Aphexda® (motixafortide) to mobilize hematopoietic stem cells for ASCT. One dosage of Aphexda + filgrastim (a growth factor) enabled a majority of myeloma patients in the clinical trial to achieve the collection goal of ≥ 6 million hematopoietic stem cells.
Next, the collected stem cells are taken to a processing laboratory, where they are frozen (cryopreserved) in liquid nitrogen and stored at a temperature of –80°C (–112°F) for later use within days, weeks, or years. Excellent function of stem cells is retained for at least 10 years.
Note: Scientific evidence indicates that “purging” myeloma cells from the harvested stem cells is not effective in ASCT for myeloma.
High-dose therapy
When you are ready to proceed with ASCT, your doctor will try to first reduce your tumor burden with myeloablative HDT, which destroys myeloma cells in the bone marrow where they grow. However, normal cells are also destroyed. The most common type of HDT used in myeloma is melphalan, administered at a dose of 200 milligrams per square meter (mg/m2) of body surface area (size of patient).
Medications are given to prevent or lessen the anticipated side effects of HDT. Common side effects of HDT include nausea, vomiting, diarrhea, mouth sores, skin rashes, hair loss, fever or chills, and infection. Patients are monitored very closely during and after the administration of HDT, including daily measurement of weight, blood pressure, heart rate, and temperature.
Stem cell rescue
Approximately 36 to 48 hours after the HDT is administered, the levels of melphalan in your blood and tissue are very low and do not harm the reinfused stem cells. Your frozen stem cells are thawed in a warm water bath and reinfused back into your bloodstream over a period of 1 to 4 hours through a catheter. The chemical used to keep stem cells fresh has a garlic smell – you may even experience the taste of garlic.
Engraftment
Engraftment is the process by which the reinfused stem cells migrate from the bloodstream to your bone marrow, where they begin to produce new
blood cells to replace the normal stem cells destroyed by HDT. You may receive SQ injections of growth factors to help stimulate your bone marrow to produce normal blood cells. Your stem cells will begin to grow back within 10 to 14 days after reinfusion, and your blood counts will begin to recover. You may receive transfusions if necessary.
Some transplant centers may require you to remain in the hospital on an inpatient basis after the reinfusion, and some centers have facilities nearby where you may stay while being monitored daily at the hospital on an outpatient basis. The length of stay varies patient-to-patient but is usually around 2 to 3 weeks. If you live near the transplant center, you may be able to sleep at home and come to the hospital for daily monitoring on an outpatient basis.
When you are discharged, your recovery will continue at home for about 2 to 4 months. Often, the most difficult time is waiting for the reinfused stem cells to engraft, for blood counts to return to safe levels, and for side effects to resolve. On some days you may feel better, and on other days you may feel too weak to do much more than sleep.
Recovery may feel like a rollercoaster ride. Frequent visits to the hospital may be required to monitor your progress. It is important to take things one day at a time. As your bone marrow produces new blood cells, symptoms resolve, the risk of serious infections is reduced, and transfusions may no longer be needed.
Depth of response
HDT with stem cell rescue delivers further improvement in the level of response achieved by induction therapy. More than half the time, partial response (PR) will be improved to either very good partial response (VGPR) or complete response (CR). The ultimate goal of HDT with stem cell rescue is to eliminate all residual myeloma cells that have not been killed during induction therapy.
Consolidation therapy
Consolidation therapy is treatment that may be given after ASCT to further deepen response, usually with the same drug regimen used for induction. Several protocols in current clinical practice include additional cycles of induction therapy after ASCT and prior to commencing maintenance therapy. Some transplant centers pursue an additional ASCT, but this is less common in the United States.
Maintenance therapy
Maintenance therapy is treatment that may be given after ASCT to prolong response. Currently, Revlimid is the only myeloma treatment approved
by the FDA for maintenance after an ASCT. Multiple clinical trials have reported higher rates of PFS and OS in patients who received Revlimid as maintenance therapy post-ASCT (vs. placebo as maintenance therapy), regardless of the depth of response following ASCT.
There is a trend of more frequent use of “doublet” (2-drug) maintenance therapy regimens, especially in patients with higher-risk myeloma. In patients with high-risk multiple myeloma (HRMM), a more intense maintenance therapy may be considered. Post-ASCT maintenance therapy remains an area of study and data is evolving.
A 2014 meta-analysis of 3,218 patients in 7 clinical trials showed that an increase in second primary malignancies (SPM) could arise from the use of Revlimid in combination with melphalan. There has been no increase in SPMs reported among relapsed or refractory patients treated with Revlimid in the absence of an alkylating agent.
Given the advantages and potential risks of post-ASCT maintenance therapy with Revlimid, discuss with your doctor your individual risk factors and your response to ASCT before making any decision.
The role of tandem ASCT
ASCT can be performed once (a “single” autologous transplant) or twice (“double” or “tandem” autologous transplants done in succession). Tandem ASCTs are usually planned with an interval of 3 to 6 months between the two transplants. Tandem transplantation for myeloma has become less common in the U.S. due to the emergence of effective novel therapies.
The role of a second ASCT
Long after a patient’s first ASCT, a second transplant may be an option for relapsed myeloma. A second ASCT appears to confer benefit. It is also a viable option for patients who achieved response of at least an 18-month duration following a first ASCT, but then relapsed. This is one of the reasons that enough stem cells for two ASCTs may be collected in advance.
Possible side effects of ASCT
Side effects are a possibility with every type of medical treatment or procedure. Each patient reacts differently at each step of the ASCT process. No two patients share exactly the same side-effect profile. The following are the most common potential side effects following HDT with stem cell rescue: nausea, mouth sores, hair loss, infection, and fatigue.
In part, the appropriate management of side effects is why it is so important to have your ASCT performed at a transplant center where the doctors, nurses, and allied healthcare professionals have performed the ASCT
procedure many times on many myeloma patients. Such a team is more likely to have the experience and the expertise to care for each individual patient’s needs.
Until engraftment of the reinfused stem cells takes place, patients are very susceptible to developing infections, and infections can cause serious complications and even be potentially life-threatening. Even a minor infection like the common cold can lead to serious complications because the body’s immune system is weakened by the effects of HDT. Special precautions are necessary during recovery. To protect the patient and prevent infection, the following supportive care measures may be required:
¡ Antibiotics may be prescribed to help prevent infection.
¡ Visitors may be asked to wash their hands, and wear masks and rubber gloves.
¡ Fresh fruits, vegetables, and flowers may be prohibited from the patient’s room as these can carry infectious agents such as bacteria and fungi.
If infection or fever occurs as a result of lowered WBC counts, the patient may be given an intravenous (IV) infusion of antibiotics.
Other side effects to be aware of and discuss with your transplant team include nausea, fatigue, mouth sores, diarrhea, and skin rash.
Life after ASCT
Data from the Health Resources and Services Administration (HRSA) demonstrate that 99.1% of myeloma patients in the U.S. are alive at 100 days following ASCT.
ASCT is more than just a medical procedure, and you will need to rely upon your doctor and other members of the transplant team, as well as on the support of your family and friends. It is not uncommon for patients to experience a loss of the sense of independence and control, while at the same time experiencing feelings of isolation, depression, and helplessness. Patients and their care partners may consider seeking assistance from a trained counseling professional. There may also be benefits to participating in patient support groups.
On average, it takes 3 to 6 months to recover from an ASCT. By this time, your bone marrow will be producing healthy blood cells and your immune system will once again be able to fight infection. Your hair will grow back, but some foods that tasted good before your ASCT may no longer taste good. In most cases, patients are able to return to normal daily activities, but it may take 6 months or more after ASCT for some patients to return to normal functioning or to full-time work.
There will be bad days and good days, and they won’t necessarily come in that order. Patients may feel differently each day during the recovery process. Patients and their care partners must take it one day at a time.
Some people believe in the intended benefits of alternative and complementary therapies, but it’s important to remember that all medicines –synthetic and natural – may interact and create unanticipated effects. Patients should always inform their doctor of all medications and therapies being taken in addition to the doctor’s prescribed protocol. Even over-thecounter products may be harmful to a patient with myeloma.
Vaccination and immunization
These terms are often used interchangeably, but vaccination is the act of introducing a vaccine into a body to produce protection from a specific disease, and immunization is the process by which a body becomes protected against that disease through vaccination. If you are planning for an ASCT, you must also make plans with your doctor to be re-immunized on a set schedule. Your re-immunization plans should be based upon local guidelines.
Current guidelines of the American Society for Transplantation and Cellular Therapy (ASTCT), European Bone Marrow Transplant (EBMT), and the Infectious Disease Society of America (IDSA) advise that re-vaccination should start between 6 and 12 months after ASCT. Additionally, these guidelines state that myeloma patients on active therapy should not be vaccinated. Please ask your doctor how this applies to your specific case of myeloma.
Relapse
Unfortunately, the majority of patients with myeloma experience a relapse after transplant is completed. The prevailing theory is that it is not the myeloma cells among the harvested stem cells that cause disease relapse, but rather the myeloma cells that remain in the body after systemic treatment.
In 2007, the journal Haematologica published the findings of the EBMT group from a large, randomized clinical trial. The study definitively demonstrated that there was no difference in relapse rate between myeloma patients who received grafts with detectable myeloma cells vs. patients receiving grafts with no detectable myeloma cells.
In December 2023, at the annual meeting of the American Society of Hematology (ASH), long-term followup results were presented of the GMMG “ReLApsE” phase III randomized clinical trial of salvage therapy with ASCT + Revlimid maintenance vs. continuous Rd for relapsed myeloma. No significant PFS or OS difference was observed in the study participants.
Other types of stem cell transplants
In addition to ASCT, there are other types of transplants.
Allogeneic (allograft) transplant
This type of transplant uses stem cells or bone marrow harvested from a donor who has been determined to be a compatible match with a recipient by means of a human leukocyte antigen (HLA) test . The donor cells are infused into the patient after myeloablative HDT. The donor’s immune system cells recognize the recipient’s myeloma cells as foreign and attack them. Unfortunately, the donor cells also attack other tissues in the recipient’s body, causing graft-versus-host disease (GVHD), which may cause complications or may even be fatal.
Reduced-intensity conditioning (RIC) allogeneic transplant
A type of an allogeneic transplant, sometimes called “mini-allo” for short. RIC transplant is a newer and, for myeloma, a safer technique than a full allogeneic (allograft) transplant because RIC transplant is non-myeloablative. RIC transplant is usually performed within 180 days after a standard ASCT.
Bone marrow transplant
A type of an autologous transplant where stem cells are collected from a patient’s bone marrow, not from a patient’s circulating peripheral blood. Currently, bone marrow transplantation is used infrequently in myeloma because the ASCT procedure is preferred. But bone marrow transplantation may be considered if stem cells are not able to be collected from the peripheral blood.
Syngeneic transplant
A type of an allogeneic transplant where bone marrow or stem cells from one identical twin sibling (donor) are infused into the other identical twin (recipient).
Matched unrelated donor (MUD) transplant
A type of an allogeneic transplant where stem cells are genetically matched to the patient but are not from a donor who is a family member. In myeloma, this type of transplant carries a high rate of GVHD and is therefore very rarely used.
Umbilical cord stem cell transplant
A type of allogeneic transplant where stem cells are harvested from multiple umbilical cords of newborns in order to obtain enough stem cells for an adult transplant. In myeloma, this type of transplant carries a high rate of GVHD and is therefore very rarely used.
ASCT in clinical trials
The use of HDT was introduced in myeloma in the 1990s, followed by the introduction of new treatment options in the 2000s. This led to improved outcomes in ASCT-eligible myeloma patients. The early clinical trials established a therapeutic approach of induction, followed by ASCT, consolidation therapy, and maintenance therapy. More recently, the use of novel therapies in each phase of myeloma treatment has significantly improved the efficacy of ASCT, including MRD-negativity.
For myeloma patients considering ASCT, the key takeaways from this booklet remain relevant as of the time of its printing, although new and updated data from clinical trials continues to be produced and presented.
If you have any questions or concerns about ASCT, speak with your doctor and visit myeloma.org/online-resources/transplant to familiarize yourself with resources that may be of interest to you.
In closing
This booklet is not meant to replace the advice of your doctors and nurses who are best able to answer questions about your specific healthcare management plan. The IMF intends only to provide you with information that will guide you in discussions with your healthcare team. To help ensure effective treatment with good quality of life, you must play an active role in your own medical care.
We encourage you to visit myeloma.org for more information about myeloma and to contact the IMF InfoLine with your myeloma-related questions and concerns. The IMF InfoLine consistently provides the most up-to-date and accurate information about myeloma in a caring and compassionate manner. Contact the IMF InfoLine at 1.818.487.7455 or or InfoLine@myeloma.org.
Terms and definitions
The following selected terms are used in this booklet, while a more complete glossary can be found in the IMF’s publication Understanding Myeloma Vocabulary located online at glossary.myeloma.org.
Apheresis: A procedure that uses a machine to separate whole blood so that one specific component can be collected while other components are immediately re-infused back into the bloodstream of the patient or donor.
Beta-2 microglobulin (β2-microglobulin, β2M, or β2M): A small protein found in the blood. High levels occur in patients with active myeloma. Low or normal levels occur in patients with early myeloma and/or inactive disease. Approximately 10% of patients have myeloma that does not
produce β2M. At the time of relapse, β2M can increase before there is any change in the myeloma protein level. Factors such as viral infection can sometimes produce elevated serum β2M levels.
Cancer: A term for diseases in which malignant cells divide without control. Cancer cells can invade nearby tissues and spread through the bloodstream and lymphatic system to other parts of the body.
Catheter: A tube that is placed in a blood vessel to provide a pathway for drugs or nutrients. A central venous catheter (CVC) is special tubing that is surgically inserted into a large vein near the heart and exits from the chest or abdomen. The catheter allows medications, fluids, or blood products to be given and blood samples to be taken.
Colony-stimulating factor (CSF): Proteins that stimulate the development and growth of blood cells. Neupogen® (filgrastim), Neulasta® (pegfilgrastim), and Leukine® (sargramostim) are colony-stimulating factors that are used to mobilize stem cells from the bone marrow into the bloodstream prior to apheresis. These may also be used after the transplant to hasten blood count recovery, or to treat low white cell count caused by therapy.
Depth of response (DpR): In myeloma, research studies have demonstrated DpR to be a predictor of statistically superior outcomes, including prolonged progression‐free survival (PFS) and overall survival (OS) in patients achieving at least a very good partial response (VGPR) during treatment.
Frontline therapy: A general term for the initial treatment used in an effort to achieve response in a newly diagnosed myeloma patient. See “Induction therapy ” and “ Response or remission.”
Graft-versus-host disease (GVHD): An immune-related reaction of donated tissue against the recipient’s own tissue.
Growth factors: Drugs that stimulate blood stem cells to both grow and be released into the bloodstream.
High-risk multiple myeloma (HRMM): Myeloma that is more likely to relapse quickly after treatment or to be refractory to treatment, as defined by the cytogenetic (chromosomal) abnormalities t(4;14), t(14;16), t(14;20), del 17p, and 1q gain, along with Revised International Staging System (R-ISS) Stage III disease, and/or a high-risk gene expression profile (GEP) signature.
Human leukocyte antigen (HLA) test: A blood test used to match a blood, tissue, or organ donor to a recipient for transfusion or transplant.
Induction therapy: The initial treatment given to a patient in preparation for an autologous stem cell transplant (ASCT). See “ Frontline therapy ” and “ Line of therapy.”
Intravenous (IV) infusion: Administered into a vein.
Line of therapy: A term used to calculate the number of therapies a patient has received. A line of therapy is 1 or more complete cycles of a regimen that can consist of a single agent, a combination of several drugs, or a planned sequential therapy of various regimens. Also see “ Induction therapy.”
M-spike: A monoclonal spike, the sharp pattern that occurs on protein electrophoresis tests, is a marker for the activity of myeloma cells. See “Monoclonal ” and “Monoclonal protein.”
Maintenance therapy: Drug or drugs given to patients to prolong remission.
Minimal residual disease (MRD): The presence of residual tumor cells after treatment has been completed and complete response (CR) has been attained. Even patients who have attained a stringent CR (sCR) may have MRD. Highly sensitive testing methods are able to detect 1 myeloma cell among 1,000,000 sampled cells in blood or bone marrow. See “MRD-negative.”
Mobilizing agent: An agent injected into a patient or donor to trigger the release of bone marrow stem cells into the bloodstream.
Monoclonal: A monoclone is a duplicate derived from a single cell. Myeloma cells are monoclonal, derived from a single malignant plasma cell in the bone marrow. The type of myeloma protein produced is also monoclonal, a single form rather than many forms (polyclonal). The important practical aspect of a monoclonal protein is that it shows up as a sharp spike on the protein electrophoresis test. See “M-spike.”
Monoclonal protein (myeloma protein, M-protein): An abnormal protein produced by myeloma cells that accumulates in and damages bone and bone marrow. It is found in unusually large amounts in the blood and/or urine of myeloma patients. See “Monoclonal ” and “M-spike.”
MRD-negative: Minimal residual disease-negative. Depending on the test, not even one myeloma cell found in 100,000 or 1,000,000 sampled bone marrow plasma cells. See “Minimal residual disease (MRD).”
Multiple myeloma: A cancer of the bone marrow plasma cells, white blood cells that make antibodies. Cancerous plasma cells are called myeloma cells.
Myeloablation: A severe form of myelosuppression, in which the consequence of high-dose chemotherapy or radiation is the complete or near-complete destruction of the bone marrow’s ability to produce blood cells. See “Myelosuppression.”
Myelosuppression: A decrease in the production of red blood cells, platelets, and some of the white blood cells.
Overall survival (OS): The median number of individuals in a group who are alive after a particular duration of time. OS is often used as a measure of treatment efficacy in clinical trials. The lengthening duration of OS in myeloma trials makes it a difficult endpoint to use, leading to the effort to validate minimal residual disease (MRD) status as a new endpoint.
Peripheral blood stem cells (PBSC): Stem cells collected from the circulating blood. These cells are similar to stem cells found in the bone marrow. The term “peripheral” means that the cells come from blood outside of the marrow.
Platelets: One of the three major types of blood cells, the others being red blood cells and white blood cells. Platelets plug up breaks in the blood vessel walls and release substances that stimulate blood clot formation. Platelets are the major defense against bleeding. Also called thrombocytes.
Progression-free survival (PFS): The length of time during and after the treatment of myeloma that a patient lives with the disease but the myeloma does not get worse. In a clinical trial, PFS is one way to measure how well the treatment is working. See “ Progressive disease.”
Progressive disease: Myeloma that is becoming worse or relapsing, as documented by tests. Defined as an increase of ≥ 25% from the lowest confirmed response value in the myeloma protein level and/or new evidence of disease.
Red blood cells (RBC): Also called erythrocytes, these cells in the blood contain hemoglobin, deliver oxygen to all parts of the body, and take away carbon dioxide. Red blood cell production is stimulated by a hormone (erythropoietin) produced by the kidneys. Myeloma patients with damaged kidneys don’t produce enough erythropoietin and can become anemic. Myeloma patients can also become anemic because of myeloma cells’ effect on the ability of bone marrow to make new red blood cells.
Refractory: Disease that is no longer responsive to standard treatments. Myeloma is refractory in patients who have had progressive disease either during treatment or within 60 days following treatment. Most clinical trials for advanced disease are for patients with relapsed and/or refractory myeloma.
Relapse: The reappearance of signs and symptoms of myeloma after a period of improvement. Patients with relapsed disease have been treated, then developed signs and symptoms of myeloma at least 60 days after treatment ended. Most clinical trials for advanced myeloma are for patients with relapsed and/or refractory disease.
Response or remission: Interchangeable terms to describe the complete or partial disappearance of the signs and symptoms of cancer.
• Stringent complete response (sCR) – sCR is CR (as defined below) plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence.
• Complete response (CR) – For myeloma, CR is negative immunofixation on serum (blood) and urine, and disappearance of any soft tissue plasmacytomas, and ≤ 5% plasma cells in bone marrow. CR is not the same as a cure.
• Very good partial response (VGPR) – VGPR is less than CR. VGPR is serum M-protein and urine M-protein detectable by immunofixation but not on electrophoresis, or 90% or greater reduction in serum M-protein, plus urine M-protein less than 100 mg per 24 hours.
• Partial response (PR) – PR is a level of response in which there is at least a 50% reduction in M-protein, and reduction in 24-hour urinary M-protein by at least 90% (or to less than 200 mg per 24 hours).
Second primary malignancy (SPM): A new cancer that is unrelated to a pre-existing cancer diagnosis. Secondary cancers that are a consequence of treatment for the initial cancer may occur months or years after the initial treatment.
Side effect: An unwanted or unexpected effect caused by a drug. Also known as adverse reaction or adverse event (AE).
Subcutaneous (SQ) injection: A method of administering medication under the skin by a short needle that injects a drug into the tissue layer between skin and muscle.
Tumor: An abnormal mass of tissue that results from excessive cell division. In myeloma, a tumor is referred to as a plasmacytoma.
White blood cells (WBC): General term for a variety of leukocytes responsible for fighting invading germs, infections, and allergy-causing agents. These cells begin their development in bone marrow and then travel to other parts of the body. Specific white blood cells include neutrophils, basophils, eosinophils, lymphocytes, and monocytes.
INTERACTIVE RESOURCES AT A GLANCE
Use the hyperlinks and web addresses included in this publication for quick access to resources from the IMF.
infoline.myeloma.org
Contact the IMF InfoLine with your myeloma-related questions and concerns
medications.myeloma.org
Learn about FDA-approved therapies for myeloma
diversity.myeloma.org
Diversity and inclusion are integral aspects of the myeloma community
videos.myeloma.org
The latest on myeloma research and clinical practice, as well as IMF webinars and other events
support.myeloma.org
Robin Tuohy
rtuohy@myeloma.org will help you find a multiple myeloma support group
publications.myeloma.org
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