Multiple myeloma is treated with a combination of drug therapy, and in many cases, a stem cell transplant. The specific plan depends largely on whether you’re healthy enough for a transplant, which is typically determined by age (usually under 65) and overall fitness. The five-year survival rate for myeloma is now 63.7%, a number that has improved dramatically over the past two decades as new drug classes have entered the picture.
Treatment generally moves through distinct phases: initial drug therapy to reduce the cancer, possible transplant, long-term maintenance drugs, and then additional options if the disease returns. Here’s what each phase looks like in practice.
Initial Drug Therapy
The first round of treatment, called induction, uses a combination of drugs designed to kill myeloma cells and shrink the disease as much as possible. This phase typically lasts four to six cycles, with each cycle spanning a few weeks. The backbone combination for many patients is a three-drug regimen that pairs a proteasome inhibitor (which blocks a protein-recycling system cancer cells depend on) with an immune-modulating drug and a steroid to enhance their effects.
Increasingly, a fourth drug is added upfront. Four-drug regimens that include a targeted antibody on top of the three-drug base have shown significantly better results in clinical trials. In one major trial, adding the antibody to the standard trio pushed the five-year progression-free survival rate to 63.2%, compared with 45.2% for the three-drug version alone. Another trial found that the four-drug approach nearly doubled the rate of deep molecular remission (48.7% versus 26.3%). These regimens are becoming the new standard, particularly for patients who are candidates for transplant.
Who Gets a Stem Cell Transplant
Autologous stem cell transplant, where your own stem cells are collected and returned to you after intensive chemotherapy, remains a cornerstone of myeloma treatment for eligible patients. Eligibility is generally based on being under 65 with no major organ problems, though some fit patients in their late 60s may still qualify.
The process works in stages. First, your stem cells are mobilized from the bone marrow into the bloodstream using growth factor injections given over four to six days. The cells are then collected through a blood-filtering procedure called apheresis. After collection, you receive high-dose chemotherapy to wipe out as many myeloma cells as possible. This intensive treatment causes a severe but temporary drop in blood cell counts, which is why the stem cells are infused back afterward to help your bone marrow recover. The transplant itself is essentially a rescue procedure that allows doctors to use chemotherapy doses that would otherwise be too toxic.
Treatment Without Transplant
For patients who aren’t transplant candidates, whether due to age, frailty, or other health conditions, treatment relies entirely on drug combinations given over a longer period. The most widely accepted first-line option pairs an antibody targeting a protein called CD38 with an immune-modulating drug and a steroid. In the landmark MAIA trial, this combination produced a median progression-free survival of nearly 62 months and overall survival exceeding 90 months, compared to about 34 and 64 months for the two-drug version without the antibody.
For patients over 75, nearly all regimens require dose reductions. A lower-intensity version of the standard three-drug combination was specifically studied for tolerability in older patients and achieved an 86% response rate with a median of 42 months before the disease progressed. Severe nerve damage, a common concern with one of the core drugs, dropped from about 35% to just 2% with the adjusted dosing.
Four-drug regimens are also moving into the transplant-ineligible setting. Trials published in 2024 showed meaningful improvements in progression-free survival when a targeted antibody was added to the standard three-drug base for older patients as well.
Maintenance Therapy After Treatment
Once you’ve responded to initial treatment (with or without transplant), you’ll likely stay on a maintenance drug to keep the disease suppressed for as long as possible. About 89% of patients on maintenance take an immune-modulating pill, typically at a lower dose than during initial treatment. The remaining patients use a proteasome inhibitor instead, particularly those with certain high-risk genetic features or kidney problems.
The current recommendation is to continue maintenance until the disease progresses or side effects become unmanageable. This can mean years of ongoing treatment. It’s a pill-based regimen for most people, taken on a regular schedule with periodic blood tests and clinic visits to monitor your response.
Protecting Your Bones
Myeloma weakens bones by disrupting the normal cycle of bone breakdown and rebuilding, often causing fractures, pain, or compression of the spine. Bone-strengthening agents are a standard part of treatment regardless of which drug regimen you’re on. Two main options are used: an intravenous bisphosphonate or a subcutaneous injection of an antibody that blocks a bone-breakdown signal. Both are given monthly, at least initially. Some evidence suggests that after the disease is controlled, the bisphosphonate may be spaced to every three months, though the data supporting this for myeloma specifically is still limited.
Managing Nerve Damage
One of the most common side effects of myeloma treatment is peripheral neuropathy, a tingling, numbness, or pain in the hands and feet caused by certain drugs. Up to 75% of patients experience some degree of nerve symptoms during treatment, and roughly 13% develop symptoms severe enough to interfere with daily activities.
The key to managing this side effect is early detection and dose adjustment. Mild tingling without pain doesn’t require a change in treatment. If pain develops or the numbness starts affecting your ability to do things like button a shirt or feel your feet, your doctor will reduce the dose. If symptoms become severe enough to limit daily activities, treatment is paused until the nerves recover and then restarted at a lower dose given less frequently. Switching from intravenous to subcutaneous delivery of the drug also reduces neuropathy risk. In the worst cases, the drug is stopped entirely.
Tracking How Well Treatment Works
Beyond standard blood and urine tests that measure myeloma protein levels, doctors increasingly use a highly sensitive test called minimal residual disease (MRD) testing to determine how deeply the treatment has worked. This test can detect as few as one myeloma cell among a million normal cells, and newer methods are pushing that sensitivity even further, to one in ten million.
Two main technologies are used. One analyzes bone marrow cells by tagging them with fluorescent markers that identify myeloma cells based on their surface proteins. The other sequences the DNA of immune cells to find the specific genetic fingerprint of your myeloma clone. Both achieve similar sensitivity levels. Reaching MRD-negative status, meaning no detectable myeloma cells at these extreme sensitivities, is associated with longer remissions and is increasingly used to guide treatment decisions.
Options When Myeloma Returns
Myeloma almost always comes back eventually, and treatment at relapse depends on which drugs you’ve already received and how long your remission lasted. For patients whose disease has progressed through multiple lines of therapy, two newer treatment categories have changed the landscape.
CAR-T Cell Therapy
CAR-T therapy involves collecting your own immune cells, genetically engineering them in a lab to recognize and attack myeloma cells, and then infusing them back into your body. Two CAR-T products are FDA-approved for myeloma, both targeting a protein called BCMA found on the surface of myeloma cells. The first was approved in March 2021, the second shortly after. These are single-infusion treatments, meaning you receive the engineered cells once. At two years of follow-up, patients treated with the newer product showed deep and durable responses. CAR-T is currently reserved for patients who have already been through several lines of treatment.
Bispecific Antibodies
Bispecific antibodies are off-the-shelf drugs that work by physically connecting your immune cells to myeloma cells, forcing them into close contact so the immune cells can kill the cancer. The first bispecific antibody for myeloma was approved in October 2022 for patients who have received at least four prior lines of therapy. In the trial supporting its approval, 61.8% of heavily pretreated patients responded, with 28.2% achieving a complete response or better. Unlike CAR-T, bispecific antibodies are given as ongoing injections rather than a one-time infusion, but they don’t require the weeks-long manufacturing process that CAR-T demands.
Both CAR-T and bispecific antibodies represent a shift toward harnessing the immune system directly, and trials are now testing them earlier in the treatment sequence, where they may prove even more effective.