New Treatments for Heavily Treated Multiple Myeloma
- Patients with multiple myeloma now have more options to potentially treat disease that has not improved after several rounds of treatment.
- The Food and Drug Administration (FDA) has approved two drugs, Talvey and Elrexfio, for patients with multiple myeloma whose disease has returned after undergoing four lines of treatment.
- Both drugs belong to a class of drugs known as bispecific antibodies, which are a novel form of cancer immunotherapy that bind to and engage two different targets.
- Side effects such as cytokine release syndrome (a condition that may cause fever, nausea, fatigue, etc.), neurological issues, and infections are possible.
The approval was based on the efficacy and safety data from phase II studies, which were presented at this year’s American Society for Clinical Oncology (ASCO) conference. Impressive findings from the MonumenTAL-1 trial showed that Talvey shrank tumors in more than 70% of patients who had received at least four prior lines of therapy.
Read MoreWhat is Multiple Myeloma?
Multiple myeloma is a type of blood cancer involving plasma cells. Plasma cells are the mature white blood cells in your bone marrow that fight against germs. These cancer cells can outnumber healthy bone marrow cells, build up in the bone marrow and spill over into the blood. They can eventually spread to other parts of the body.The current approach to therapy is a combination of a targeted drug, biological therapy, steroid, chemotherapy, and stem cell transplant.
Bispecific antibodies including CAR T-cell therapy are the newest class of medication approved for patients with relapsed/refractory multiple myeloma — and have been shown to be effective. Bispecific antibodies work by helping your immune system to recognize and attack cancer, but they are not for everyone. If you’re diagnosed with multiple myeloma, it’s worth discussing this with your doctor.
How Bispecific Antibodies Work for Multiple Myeloma
Bispecific antibodies are a type of immunotherapy that helps your immune system to fight your myeloma cancer cells.
These are proteins that have two arms to engage two targets, one on the surface protein of myeloma cells, and one on the CD3 receptor, which is located on the surface of T-cells (immune system cells). The drugs bring the myeloma cells close to your immune cells and activates the immune system in your body to kill the myeloma cells.
What are Bispecific Antibodies?
Over the last few years, there have been tremendous advancements in clinical trials that have provided innovative treatment options for multiple myeloma. CAR T-cell therapy (ide-cel and cilta-cel) is often used as a fourth-line option after people have tried and failed to respond to three other treatments including a proteasome inhibitor (Velcade), an immunomodulatory agent (Revlimid), and an anti-CD38 monoclonal antibody (Darzalex).
CAR T-cell therapy can be a time-consuming process since your own immune T-cells are removed from your blood and genetically modified to fight against cancer before being put back into your body.
To solve this problem, “an off-the-shelf approach” has been investigated. “Off-the-shelf approach” uses your own immune system to fight against cancer.
Bispecific antibodies are “an off-the-shelf approach to using the body’s immune system to treat cancer,” Dr. Stephen Schuster, a medical oncologist at Penn Medicine, told SurvivorNet in a previous chat. “That means there’s no need to collect a patient’s cells and do gene therapy on them to direct them against the cancer.”
One such treatment is BiTE (bispecific T-cell engager) antibodies that have been approved for multiple myeloma and are available as an off-the-shelf treatment. BCMA protein is heavily present on the surface of tumor cells in myeloma, and that makes BCMA-targeted agents such as Elrexfio and Talvey an attractive therapeutic strategy in multiple myeloma. Talvey is a first-in-class drug that has a new target called GPRC5D found on the surface of myeloma cells.
Promising New Approvals
In the MonumenTAL-1 trial, 187 adults without any prior BCMA-targeted therapy who had received at least four prior lines of therapy received Talvey as their first BCMA-directed therapy.
In this group of patients, the drug shrank tumors in 73% of patients with an estimated 33% of patients achieving a complete response. Similar tumor shrinkage activity was observed among 32 patients who were exposed to prior BCMA-directed therapy.
“The approval of Talvey, our fifth innovative therapy and second bispecific antibody approved for the treatment of multiple myeloma, demonstrates our commitment to expanding our portfolio of medicines to help address unmet needs for patients who continue to face challenges with this complex hematologic malignancy,” said Dr. Peter Lebowitz in a statement from Janssen Research & Development, LLC.
Another off-the-shelf drug, Elrexfio, is currently the third BCMA-targeted drug on the market. Its approval is based on the MagnetisMM-3 trial.
In an interview with Pfizer, Dr. Ajay Nooka, of the Winship Cancer Institute of Emory University in Atlanta, stated: “By offering durable clinical response with an established safety profile and the convenience of subcutaneous administration, Elrexfio provides a much-needed new option for heavily pretreated multiple myeloma patients who are struggling with relapsed myeloma.”
The study shows 61% of study participants responded to treatment and 35% of patients had a complete response. In addition, a 33% response rate was observed among the patients who also received prior BCMA-directed therapy.
The Potential for Side Effects
Talvey and Elrexfio are both bispecific antibodies, which have potential side effects people should be aware of.
Dr. Catherine Diefenbach, Director of the Clinical Lymphoma program at Perlmutter Cancer Center, previously told SurvivorNet that, “as a class, bispecific antibodies tend to have some of the same side effects as CAR T-cell therapy but at a much lower level.
“[They] all generally tend to occur in the first cycle of therapy, sometimes the beginning of the second cycle. Subsequently, there is very low toxicity with these therapies,” she added.
The most common side effects associated with the medication include:
- Cytokine release syndrome (a condition with may cause fever, nausea, and fatigue)
- Neurologic toxicity
- Infections
- Decreased blood counts
- Elevated liver enzymes
Cytokine release syndrome (CRS) and neurotoxicity are the biggest worry and can lead to serious problems. Cytokines act as a messenger to coordinate immune responses in your body. These medications may trigger damaging inflammation leading to CRS. You may experience headaches, fever, rash, fast heartbeat, difficulty breathing, and low blood pressure.
In more serious cases, these medications can cause inflammation of the central nervous system, leading to neurological symptoms.
In most people, the symptoms are mild. However, it’s important to talk to your doctor about any symptoms you experience while on these drugs. In some cases, the medication may need to be held or stopped. Your doctor may also recommend you be hospitalized for close monitoring as a precaution due to the risks of CRS and neurological toxicity.
Even though the benefits of treatment may be greater, it’s always a good idea to be aware of the potential side effects of Talvey and Elrexfio before starting the treatment.
Questions to Ask Your Doctor
If you or a loved one has been diagnosed with relapsed/refractory multiple myeloma, please discuss the use of bispecific antibody treatment with your doctors. Here are some questions you may want to consider asking:
- What will treatment with Talvey/Elrexfio cost?
- How often do I need to take the medications?
- How will I feel during treatment?
- Is it possible that I will have lingering side effects?
- How will treatment affect my life?
- What are the advantages and disadvantages of Talvey and Elrexfio
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