Receiving a diagnosis of multiple myeloma can be overwhelming, and one of the most challenging aspects to accept is that treatment is not a one-time event, but rather a long-term process. This journey involves multiple stages, and understanding what to expect can help individuals better prepare themselves. Multiple myeloma is a type of cancer that affects plasma cells, which are a specific type of white blood cell found in the bone marrow. Although it is one of the more treatable forms of blood cancer, a cure remains elusive for most patients.
The treatment of multiple myeloma typically involves a series of therapies administered over time, with each treatment plan referred to as a “line of therapy”. When one treatment stops working, the patient and their care team will consider the next course of action. To gain insight into this process, we consulted with two experts in the field of multiple myeloma: Adeel Khan, MD, a hematologist-oncologist and epidemiologist at UT Southwestern Medical Center in Dallas, and Tulio Rodriguez, MD, a hematologist-oncologist and director of the Bone Marrow Transplant and Cellular Therapy Program at City of Hope Cancer Center Chicago.
Why Is Multiple Myeloma Treated in Stages?
According to Dr. Khan, multiple myeloma is treated as a sequence of therapies because there are now numerous effective drug classes available, making it impractical and unsafe to use all of them simultaneously. As a result, doctors must carefully decide which treatments to use and when. Dr. Khan stated, “Myeloma is treated as a sequence of therapies because there are now so many effective drug classes that it is neither feasible nor safe to use all of them at once.”
There is no single optimal sequence of treatments, as multiple myeloma can change over time. Each treatment aims to control the disease while preserving future options. Doctors also consider the likelihood of relapse when planning treatment. As Dr. Khan explained, “As of 2026, the field is now seriously discussing functional cure for some patients, but cure remains elusive for most.” A functional cure refers to a state where the disease remains under control and behaves as if it were gone, even though a cure has not been confirmed.
Relapse is a common occurrence in multiple myeloma, and it is not a reflection of anything the patient did wrong. Dr. Khan noted that “Relapses are common because residual resistant myeloma cells often persist below the level of detection, then expand for reasons we do not understand.”
The initial phase of treatment is called induction. In recent years, induction has shifted from three-drug combinations (triplets) to four-drug combinations (quadruplets) for many patients, according to Dr. Khan.
What Is a Common Four-Drug Combination for Multiple Myeloma?
One common four-drug combination is Dara-RVD, which consists of:
- Daratumumab: A targeted antibody that attaches to a protein on myeloma cells
- Lenalidomide: A medication that strengthens the immune system’s response to myeloma and helps slow the growth of cancer cells
- Bortezomib: A medication that blocks myeloma cells from breaking down unwanted proteins
- Dexamethasone: A steroid that helps destroy myeloma cells and can also reduce inflammation and ease some side effects caused by treatment
Four-drug combinations have become the standard of care. Dr. Khan stated, “There is ample data to support quadruplet use in most settings, and the NCCN’s 2026 myeloma guideline states that the panel prefers four-drug regimens as standard primary therapy, especially for transplant candidates.” The National Cancer Network (NCCN) is a group of leading cancer centers that publishes widely followed treatment guidelines.
During the initial few months of treatment, the focus is on reducing the amount of myeloma in the body, according to Dr. Rodriguez. As symptoms such as bone pain, fatigue, or anemia improve, patients may start to feel better. Regular appointments and blood tests are used to measure the response to treatment and check for side effects.
Dr. Rodriguez noted that “Some common side effects include changes in blood counts, increased risk of infection, and numbness or tingling.” Fortunately, severe nausea and vomiting are uncommon. The care team may adjust medications or doses based on how well the treatment works and how the patient tolerates it.
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For many years, an autologous stem cell transplant was considered the next step after initial treatment. However, with the development of more effective non-transplant treatments, this is no longer the automatic next step for everyone. Dr. Khan explained that “This has become an increasingly complex and sometimes controversial decision because our non-transplant therapies are much better than they used to be.”
A transplant requires a significant commitment of time and energy and can cause serious side effects. The decision to undergo a transplant depends on various factors, including overall health, physical fitness, disease characteristics, and personal preferences. A transplant can provide lasting disease control, especially for patients with high-risk myeloma. Dr. Khan cited the DETERMINATION trial, which found that an early transplant increased progression-free survival (the length of time a person lives without the disease getting worse), although it did not find a difference in overall survival.
Preparing for a Stem Cell Transplant
If a transplant is deemed the best course of action, preparation should begin early. Dr. Rodriguez recommends several steps to prepare for a transplant, including eating nutritious foods, staying active, addressing dental issues and infections, arranging help from family or friends, and planning for time away from work and daily activities.
Recovery begins as the transplanted stem cells start producing new blood cells. Most patients continue to improve over several weeks or months, although recovery times vary.
Preparing for and Choosing Multiple Myeloma Treatments
For CAR T-cell therapies like ide-cel, patients must have received at least two prior treatments, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Bispecific antibodies, such as teclistamab combined with daratumumab, may be used after at least one prior treatment line.
Treatment decisions at relapse depend on factors like how quickly the disease returned, previous therapies, disease burden, blood cell counts, infection risk, and patient preferences. Maintenance therapy, a lower-intensity treatment, aims to control myeloma long-term but can disrupt daily life. Adjustments or alternative treatments may be considered if challenges arise. Open communication with the care team is essential for managing both medical and emotional concerns during remission and relapse.
Treating Relapsed Multiple Myeloma
Treatment for relapsed multiple myeloma has undergone significant changes in recent years. Immune-based therapies, once reserved for later stages, are now being used earlier in the treatment process. Two key immune therapies are CAR T-cell therapy and bispecific antibodies.
CAR T-cell therapy involves collecting and modifying the patient’s immune cells to target and attack myeloma cells. Ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) are two types of CAR T-cell therapy used after specific previous treatments.
Other treatments in development include new CAR T-cell therapies, bispecific antibodies, and CELMoDs (cereblon E3 ligase modulatory drugs). At the time of first relapse, patients and their doctors may consider CAR T-cell therapy, bispecific antibodies, or another drug combination.
After initial treatment and, for some patients, a transplant, maintenance therapy may begin.