Myeloma patients need to be vigilant due to their immunocompromised status. Whether actively fighting myeloma or in a complete response, many patients continue to worry about other infections and diseases that might come their way. What steps should be taken to prevent infection? How can patients enjoy a high quality of life while still being cautious or protective?
As we all know, this discussion is extremely pertinent due to the COVID-19 pandemic from which the world seems to be moving on. This leaves immunocompromised patients, such as multiple myeloma patients, at unease, wondering how they can fully adjust back to society while still taking preventative measures.
On May 25th, 2022, Dr. Ben Derman gave his opinion and expertise on this subject to the Relapsed/Refractory Myeloma Patients Chapter. You can watch his presentation or read the highlights from the talk below.
Why Multiple Myeloma Causes Infections
Understanding what multiple myeloma is can help us better understand why things go awry with infections within this population. Multiple Myeloma is a blood cancer derived from plasma cells in the bone marrow. Plasma cells make antibodies (synonymous with immunoglobulins).
Antibodies play an important role in preventing and recognizing infections. Their purpose is to locate and attack foreign proteins or antigens in the body. They label them as "dangerous" or "foreign" and then recruit cells to rid the body of that which is dangerous or foreign (such as infections).
Multiple myeloma patients are SEVEN times more likely to get an infection than a myeloma (and cancer) free individual. What puts myeloma patients at such high risk?
A major reason for this increased risk is the lack of immunoglobulins (antibodies) in a myeloma patient, due to the body making cancerous plasma cells instead of good ones. There are also decreased lymphocytes (a type of white blood cell in the immune system) and neutrophils (another type of white blood cell).
There is also an increase of cytokines (chemical messengers) that inhibit helper T-cells from preventing and fighting infections (a type of lymphocyte).
In layman's terms, myeloma patients aren't making healthy antibodies to recognize and kill infections in the body. In addition, patients are actively taking treatments whose sole purpose is to target and destroy plasma cells, and while most medicines succeed in myeloma cell death, that doesn't mean that other healthy plasma cells don't suffer the same fate. Thus the immune system of a myeloma patient loses its ability to recognize, fight, and destroy infections due to the lack of healthy antibodies whose mission is to prevent such infections.
Infection, therefore, is the leading cause of death in myeloma. In fact, the first 2 to 3 months after diagnosis is when myeloma patients are at the highest risk of death due to infection.
Unfortunately, newly diagnosed patients aren't the only ones who need to be cautious about infections. While it's true that the higher the tumor burden (or amount of myeloma in the body), the higher the risk patients have for infection, another truth is that the longer that a myeloma patient's immune system is suppressed due to longevity of life while on maintenance therapy or other treatments, the higher the risk for infection as well. This is why myeloma patients truly are facing a double-edged sword when it comes to infection.
What Infections Are Most Serious for Myeloma Patients
However, this doesn't mean that the common cold will be the demise of every myeloma patient, rather, there are certain infections to watch for and prevent throughout all stages of your myeloma journey.
These infections are:
- VZV (shingles)
- Bacterial infections
- Upper respiratory infections (viruses)
- CMV (cytomegalovirus)
Let's break down what to watch for and how to prevent the aforementioned infections.
Ironically, myeloma as a disease itself doesn't significantly increase the risk for VZV (shingles), but rather the medications are taken to fight myeloma increase the risk of this infection. Proteasome inhibitors such as Velcade, Kyprolis, or Ninlaro increase the risk of herpes in a multiple myeloma patient. In fact, those myeloma patients on PIs have a 2.6x higher risk of contracting herpes (especially shingles) than those who don't have a PI (Velcade, Kyprolis, or Ninlaro) as a part of their treatment.
So what do you need to watch for? Shingles is a linear, painful and itchy rash with fluid-filled vesicles. As time goes on, those vesicles pop and it scabs over. It's highly contagious during the vesicle phase, it's very important to make sure that you are not exposed to anyone that has shingles or any children that might have been around someone with shingles. Other infection preventions are mentioned later in the article.
Bacterial and Upper Respiratory Infections (Viruses)
These are the common illnesses that we see such as:
- Strep pneumonia, staph aureus (common bugs)
- E.coli and other similar bugs (GI tract)
- Rhinovirus, RSV, human metapneumovirus, non-COVID coronavirus, influenza (run of the mill "scares")
Doctors see most of these illnesses present in the respiratory tract of a myeloma patient, but they also present in the urinary tract and skin or soft tissue.
You can do your best to prevent these diseases by practicing good hygiene (such as thorough handwashing) and being cautious about being around those who are sick.
This is less commonly looked at and it's less of a concern for those patients that haven't been exposed to CAR T therapy. There is definitely something about the chemotherapy (lymphodepletion) for CAR T that leads to the reactivation of CMV.
The reason this is important is that most of us (50-70% of the population) have been exposed to CMV but it lies dormant in our bodies until something (such as an intense therapy) suppresses the immune system. Doctors will not find this unless they look for it, so patients undergoing CAR T need to be monitored for it. Make sure your physician keeps this in mind if you are considering CAR T therapy.
There is so much that we don't know about COVID-19 (still!) and it seems like information is always changing as new discoveries are being made. However, there are some things that we do know that can be helpful for us as we look to prevent or treat COVID-19 and keep it from becoming a life-threatening illness.
- Myeloma patients are 2x more likely to develop COVID.
- 54% of myeloma patients have neutralizing antibodies (those that can develop an immune response) after 1st vaccine
- 16% had undetectable antibodies against COVID-19 after 2 therapies (especially those being treated with daratumumab or other immunotherapies), meaning, they did not present with antibodies that could help develop an immune system if they contracted COVID-19.
It's highly recommended that all myeloma patients receive a COVID-19 vaccination schedule that complies with CDC recommendations. This means 2-3 initial shots (depending on when your first injection is/was) and 2 boosters.
Infection Prevention Strategies for Multiple Myeloma
All myeloma patients are going to be in different stages of their treatment or disease with varying levels of risk, so while we are going to share infection prevention strategies today please be aware that "infection prevention" might look different for everyone.
Newly Diagnosed Patients
As stated before, the highest risk of death due to infection for myeloma patients is between 2-3 months after diagnosis. Different clinical trials have tested different antibiotics with patients to see what would be more effective in preventing or treating infection. This has led to the discovery of successful antibiotics, such as levofloxacin to prevent infections that could be harmful to patients.
Therefore, Dr. Derman uses the following protocols in order to help his newly diagnosed myeloma patients to prevent infection.
Dr. Derman's focus for newly diagnosed patients includes shingles prophylaxis (or prevention) with Acyclovir at a 400 mg twice-daily dose. His next priority is preventing antibacterial infections for those that are neutropenic (meaning that they have low white blood cell counts) or those that have a high percentage of myeloma cells in their bone marrow, meaning that they are likely to be neutropenic. He uses the aforementioned levofloxacin for these patients.
For those that need it, he and his team do provide Anti-PCP and Anti-Hepatitis B prophylaxis, although these are not needed for all patients.
Post-SCT (Stem Cell Transplant)
High-dose melphalan wipes out the immunity of a myeloma patient, erasing immunity that has been gained over decades, by causing lymphodepletion (inhibiting or destroying cells that make up your immune system).
Dr. Derman uses the following in order to prevent infection in myeloma patients who have just received a stem cell transplant.
As a rule, Dr. Derman uses levofloxacin and fluconazole as prophylaxis (protection) from antibacterial and anti-fungal viruses for around two weeks, until the patients are leaving the hospital.
While Dr. Derman and his team have been using a higher dose of Acyclovir (800 mg), they are going to change it to a regular dosing, and for those that are in need of Anti-Hepatitis B or Anti-PCP prophylaxis, the proper medications are administered.
The most important is to adhere to a vaccination schedule, that includes COVID re-vaccination, that should have been provided to you by your transplant doctor. If for some reason you are unsure or unfamiliar with your re-vaccination schedule, you should contact your transplant team for clarification.
Your doctor, nurse, and caregiver team should be very vigilant post-transplant to watch for any signs of infection. Make sure to communicate openly and honestly about how you are feeling. Watch for fevers. Although 50% of fever-causing "bugs" post-transplant cannot be identified, this doesn't mean that those infections cannot be treated. Antibiotics can be given and can be life-saving!
Post CAR-T Cell Therapy
A lot of the protocols post-CAR-T therapy are similar to those after stem cell transplant. The difference is the Anti-CMV prophylaxis due to the possible reactivation of CMV. Whether low-level or high-level, Valganciclovir (different than acyclovir) can prevent or treat this virus. There, of course, needs to be a delicate balance between preventative treatment and maintaining adequate blood counts, which makes this more complicated than it seems and therefore needs to be reviewed and discussed between a myeloma patient considering CAR-T Therapy and their medical team.
COVID Precautions (May 2022 Edition)
Finally, here are the COVID precautions and preventions for myeloma patients as of May 2022.
As you can see above, and as we mentioned earlier in the article, it's imperative that myeloma patients receive adequate COVID vaccination in order to prevent them from contracting a more serious version of the disease.
Evusheld is also given to patients before a stem cell transplant or CAR T cell therapy. A common question in the myeloma community is why those Evusheld antibodies would be given to patients right before their immune system gets wiped out. The rather simple answer is that the melphalan (the potent chemotherapy given as a part of the stem cell transplant procedure) targets plasma cells, not the antibodies themselves.
We have learned that plasma cells are in charge of creating antibodies for your protection against infection, so when those cells are wiped out due to the intense chemotherapy, you are left with little to no immune response against COVID or other infectious diseases. However, if Evusheld is given, those COVID-19 antibodies survived (again, because they weren't the target of the melphalan) and therefore the patient still has some level of protection from the illness that has been plaguing us for the past two and a half years.
There are successful treatments for those who are infected with COVID, though responses vary and if you are diagnosed with COVID you should be monitored by a doctor.
- Patients with multiple myeloma are at a high risk of infection, especially in the first three months and after Stem Cell Transplant or CAR T Therapy.
- Their high risk comes from decreased antibody production and other effects on the immune system.
What can be done?
- Shingles protection is a must for all (whether through acyclovir or the shingles vaccine, although acyclovir has proven to be more efficient)
- COVID protection is variable, there is no one size fits all approach, but we should be wise in our infection prevention (masks, hand washing, social distancing)
- There are antibiotics and other preventative measures that can be taken in order to reduce infection risk.
Don't forget to check out the Q&A section of the video in order to learn more about this subject and how we can stay safe while still enjoying a good quality of life.
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about the author
Audrey is the Editor for the HealthTree Foundation for Multiple Myeloma. She originally joined the HealthTree Foundation in 2020 as the Myeloma Community Program Director. While not knowing much about myeloma initially, she worked hard to educate herself, empathize and learn from others' experiences. She loves this job. Audrey is passionate about serving others, loves learning, and enjoys iced chais from Dutch Bros. She also loves spending time with her supportive husband and energetic three-year-old.