What’s New in Second-Line Treatment for Multiple Myeloma?
- Immune-based treatments are changing what it means to live with multiple myeloma, offering new ways to control the disease while preserving quality of life.
- New immune therapies, such as CAR T-cell therapy and bispecific antibodies, can help the immune system fight myeloma more precisely with less toxicity than older treatments.
- With multiple immune-based options available or emerging, patients should have meaningful conversations with their care teams about what matters most in their lives — whether it’s time off treatment, convenience, or long-term control — to decide which treatment approach works best for them.
- For example, Dr. Sagar, Lonial, a hematologist/oncologist at Emory University, explains that when comparing CAR T-cell therapy to bispecific antibodies, patients should consider if a treatment like CAR T is worth the initial side effects. “With a CAR T approach … perhaps the toxicity upfront may be a little bit more, but the upside down the road is that you’re on no treatment and that you’re sort of smooth sailing,” he explains.
When myeloma returns after initial therapy, this is called first relapse or second line treatment. Traditionally, second-line therapy included combinations of chemotherapy-like drugs, steroids, and antibodies that target myeloma cells. Recently, new immune-based treatments have shown impressive results, changing how doctors treat patients early after relapse.
Read MoreNew Approaches in Second-Line Therapy
Two of the most exciting new second line treatments are:- Bispecific T-cell engagers: Teclistamab plus daratumumab, a combination using a immune T-cell engaging therapy, work together to help the body attack myeloma cells.
- CAR-T therapy: With ciltacabtagene autoleucel (Cilta-cel), a patient’s own immune T cells are reengineered to attack myeloma cells.
Both therapies were first used after many treatments had already been tried, but recent studies show they can be very effective earlier, right after first relapse.
Bispecific T-Cell Engagers
A clinical trial (called MajesTEC-3) tested teclistamab plus daratumumab in patients whose myeloma had returned after one to three previous treatments. Teclistamab engages immune T cells to recognize and attack myeloma cells. Daratumumab targets a protein on myeloma cells.
Patients had longer control of their myeloma, were less likely to have disease progression or death, and more achieved complete responses and no measurable residual disease (MRD), meaning very deep remission. However, infection risk is increased with this treatment because the immune system can be temporarily weakened. Most infections were manageable with monitoring and treatment. From this remarkable data, this treatment is currently under review by the Food and Drug Administration (FDA).
This approach has many pros: it is readily available so treatment can start quickly and is often available in community cancer centers. Treatment is ongoing, but flexible and easier to adjust if needed.
However, it does require ongoing treatment, and the immune system can be temporarily weakened, increasing infection risk.
CAR T-Cell Therapy
CAR-T therapy (Cilta-cel) is a personalized treatment made from a patient’s own immune T cells. The T cells are collected, modified in a lab to attack myeloma cells, and infused back into the patient as a single infusion. It was initially used for patients who had already received many treatments, but it is now approved for earlier use if myeloma is no longer responding to lenalidomide.
Many patients experience long-lasting control after just one infusion, often without ongoing therapy. Deep responses (negative for MRD), are common.
Side effects can include:
- Cytokine release syndrome (CRS) or widespread inflammation due to immune response
- Neurologic effects such as confusion or trouble speaking
- Increased risk of infection while the immune system recovers
Rare complications, including immune-related bowel inflammation and delayed neurologic effects, have been reported.
It is usually given as a single infusion, often leading to long treatment-free periods and deep, durable responses.
Unfortunately, CAR T-cell therapy does require specialized centers, takes several weeks to prepare, and can cause stronger immune-related side effects as well as some rare delayed toxicities.
Which Approach Is Right For You?
Both are immune-based treatments, but they differ in how they are given and how they fit into daily life. Choosing between these options depends on disease characteristics, overall health, access to specialized treatment centers and personal preferences.
Both therapies have strong evidence, but there is no direct comparison, so the “best” second-line therapy is individualized. Over time, many patients are likely to receive both treatments, though the optimal order remains unclear.
“I think these become the kinds of conversations that we have with patients in first relapse. Do you want to go with a CAR T approach where perhaps the toxicity upfront may be a little bit more, but the upside down the road is that you’re on no treatment and that you’re sort of smooth sailing? Or do you want to do something like [bispecific] where the toxicity is clearly lower but you are on a little bit more longer term therapy? Those are the kinds of discussions we’re going to have with patients,” Dr. Lonial explains.
Questions To Ask Your Doctor
- Which treatment options are available for my situation, and how do they work?
- Am I eligible for these therapies?
- Are these treatments available at my local cancer center, or would I need to travel?
- How quickly would I need to start treatment, and how soon could I see benefits?
- What are the potential side effects and how can they be managed?
- How might these treatments affect my daily life, work, or travel?
- Are there risks of infection or other complications I should watch for?
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