This article presents a Q&A with MMRF Patient Navigation Center nurses Grace Allison and Brittany Hartmann on key takeaways from the 2024 annual meetings of the National Comprehensive Cancer Network (NCCN) and the Journal of the Advanced Practitioner in Oncology (JADPRO) on recent multiple myeloma treatment advances.
Low white blood cell, red blood cell, and platelet counts commonly occur with many different myeloma therapies, and they are seen even more frequently in patients receiving CAR T-cell therapy.
Because low white blood cell counts increase the risk of infections, medications called growth factors (for example, filgrastim) may be given to patients who receive CAR T-cell therapy. These drugs help the body produce white blood cells. Low red blood cell counts can cause fatigue and shortness of breath and are usually treated with blood transfusions or drugs (for example, erythropoiesis-stimulating agents) to help the body make more red blood cells. For low platelets, which raise the risk of bleeding and bruising, platelet transfusions may be necessary in severe cases.
Infections are also a common side effect of CAR T-cell therapy. Before starting treatment, patients are usually given medications to prevent infections—for example, acyclovir to prevent viral infections. Antibiotics and antifungals are commonly given, as well. Intravenous immunoglobulin (IVIG), which boosts a patient’s immune system following CAR T-cell therapy, is also often given. As another strategy for infection prevention, many treatment centers are re-vaccinating patients following CAR T-cell therapy.
If a fever develops after CAR T-cell therapy, even if it’s just low grade, patients should immediately report it to their care teams. The doctor will investigate to see if it’s caused by an infection. This may require blood tests and possibly a chest x-ray to rule out the possibility of an active infection.
If there’s no sign of infection, the doctor will see if the fever is caused by a reaction called cytokine release syndrome or CRS. In CRS, the body’s immune system gets revved up too high, resulting in an overreaction that can cause fever, chills, fatigue, muscle aches, nausea, and a fast heartbeat. In more serious cases, CRS can cause problems with the lungs, liver, or heart. Fortunately, CRS is a condition that the care team will be ready to address. Treatments for CRS include tocilizumab and steroids.
Side effects that are of particular concern are lesser-known neurotoxicities, including a condition called immune effector cell-associated neurotoxicity syndrome—better known as ICANS. In ICANS, inflammation interferes with the brain, leading to symptoms like confusion, difficulty speaking, headaches, and feeling very sleepy. In more serious cases, seizures or changes in alertness can occur.
ICANS typically occurs within a few days of receiving CAR T-cell therapy. The duration varies, but the condition usually resolves within 1 to 2 weeks with appropriate management. To manage ICANS and other neurotoxicities, the care team will usually consult with a neurologist. Management strategies can include using anti-seizure medications.
Another concern is more serious Parkinsonian-like syndromes, which are conditions that cause symptoms like those seen in Parkinson’s disease, such as stiffness, tremors, and balance problems. In studies, some patients who received the CAR T-cell agent Carvykti developed Parkinsonian-like syndromes 40 to 60 days after treatment. The symptoms may persist, requiring long-term management and supportive care.
As with CAR T-cell therapy, CRS and ICANS can develop in patients receiving bispecific antibody therapy. CRS is more common than ICANS, but the risk for both is much lower with bispecifics than with CAR T. When these conditions develop, it’s usually at the beginning of treatment, during the step-up doses. This is why these doses are given in a hospital or other treatment facility. After all the step-up doses have been completed, the risk of CRS and ICANS is lower.
Bispecific antibodies can weaken the immune system, increasing the risk of infections. Patients and caregivers should be vigilant for signs of infection such as fever, chills, or a persistent cough. Maintaining open communication with your healthcare team about any symptom is important.
The bispecific antibody Talvey has some unique side effects. Talvey targets a protein called GPRC5D, which is present on myeloma cells. It’s also present on other cells in the body, including those found in the mouth, skin, and nails. Because of this, Talvey can cause side effects in these parts of the body, such as a full-body rash, peeling of the skin, and changes in the fingernails. Though inconvenient and unpleasant, these side effects rarely create difficulty with daily activities and instead tend to be quality-of-life issues.
Oral side effects can include taste changes and mouth sores. Difficulty swallowing is another possible side effect and can be concerning, because it can cause lack of appetite, which can lead to weight loss. Proper nutrition is important not just to maintain day-to-day health but especially to help fight off myeloma and the side effects of myeloma treatment.
Care teams often recommend a thick barrier lotion like Aquaphor for rashes and peeling. Other products are available to help strengthen and protect the nails. For oral side effects, special mouthwashes (for example, dexamethasone) can be used for dry mouth.
Consulting a nutritionist early on is important, as a nutritionist can recommend strategies for coping with mouth problems such as mouth sores, changes in sense of taste, dry mouth, and difficulty swallowing before they become a serious issue that interferes with eating.
For patients with comorbidities, early referral to a nutritionist is important. Additionally, physical therapy for strength maintenance and muscle protection can help patients maintain their quality of life.
One presentation at NCCN noted that a strategy for balancing comorbidity management and myeloma treatment is a drug holiday—that is, a period where a patient does not take any medication. This is particularly an option when the myeloma is well controlled. This strategy can make patients nervous that the myeloma will come roaring back. Care teams, however, are very much on board with drug holidays when appropriate, and they don’t fear that it will affect long-term outcomes.
CELMoDs, a new class of myeloma drug, work like immunomodulators such as Revlimid and Pomalyst and are orally administered. They help the immune system recognize and attack myeloma cells, and they kill myeloma cells directly. CELMoDs have been shown to be effective even in patients whose myeloma has become resistant to some treatments.
One point that came up at JADPRO was the importance of making CELMoDs and oral agents more widely available—for instance, to patients being treated in community facilities. Expanding the availability of these agents would make these treatments accessible to patients who do not live near specialized treatment facilities and could also reduce or eliminate the need for patients to spend time receiving infusions. Overcoming these barriers offers the potential to improve patient quality of life while also providing treatments that have shown to have great responses.
We know that the percentage of myeloma deaths is higher in Black, Latinx, and LGBTQ+ patients, largely because of unequal access to care and lower rates of early detection and screening. The fact that there is an awareness of this discrepancy, and that it’s being discussed, is an important step forward. This is an area that the MMRF is actively addressing by raising awareness among and providing education to care providers.
Other efforts to improve care equity have focused on making participation in clinical trials easier for a broader population of patients. Strategies like offering travel assistance and expense reimbursement, and opening trials in smaller community settings and not just large academic hospitals, allow patients from rural areas to participate.
Finally, helping patients manage treatment-related costs is another area that has received greater attention. This can involve helping patients navigate the ever-changing landscape of insurance or offering programs that provide financial support. Receiving CAR T-cell therapy involves a significant commitment and can disrupt daily life, including work responsibilities. At present, this treatment requires travel to a specialized medical center, which for many patients will be far from home, adding time and logistical challenges. This time away from work and daily life can be a burden, both emotionally and financially. Several organizations have developed programs to provide financial support for treatment-related expenses, such as the cost of medication, travel to a treatment center, and hotels.
