Transcript
[0:04] Associate Professor Ben Teh is an infectious diseases physician and clinical researcher at Peter MacCallum Cancer Centre and the National Centre for Infections in Cancer. His research interests in the area of infections in cancer patients encompass translational immune profiling for infection risk prediction, clinical studies of infection risks with new cancer therapies, and clinical trials of vaccination in hematology patients. Today we are very lucky to have Ben speaking to us about infection prevention and strengthening immunity.
[0:39] Nel: So, welcome Ben. Thanks so much.
Ben: Thanks Nel for the kind introduction and certainly thanks to Myeloma Australia for the kind invitation to speak today. Before I start, I just wanted to declare my disclosures. I do apologize that some of the slides are more technical and clinically focused, but I’ll try my best to put it into context for everyone.
So, before we can talk about preventing infections in patients who have myeloma, it’s important to think about what patterns of infections we see. The first thing, as you can see from this slide, is to consider the different phases of myeloma treatment—from when people first start treatment, to those who are transplant eligible, and later on during disease progression. The patterns of infection can be very different. At the start, it tends to be more bacterial infections, whereas during stem cell transplant there are different phases. In the early days after transplant, bacterial infections are more likely, but later on viruses become more important, especially viruses we’ve encountered before which can reactivate, or new viruses like COVID-19 and influenza.
[2:36] There are also associations with particular therapies. For example, proteasome inhibitors are associated with herpes zoster (the chickenpox virus) reactivating. The use of high-dose steroids is associated with an unusual type of fungal infection called Pneumocystis. That’s why many myeloma patients on corticosteroids like dexamethasone are also on preventative treatment during that time. This slide summarizes the different infection patterns across the phases of myeloma treatment and with certain types of treatment.
[3:32] These summary slides give a flavor of how infection rates can change depending on the treatment. When starting out, infection rates generally range between 10 to 20%. With monoclonal antibody therapies like daratumumab or isatuximab, used when disease is more active, we see a slightly higher rate, between 20 to 30%. But these are things we anticipate and can try to reduce the risk for.
[4:25] For newer generation therapies like bispecific antibodies and CAR T-cell therapy, which are new in myeloma, these are early reports of infection patterns. We are still learning.
In terms of infection risk, I think about several factors. At a patient level, how active someone is affects risk. Then there are risks connected to the myeloma itself, like a higher disease burden or low blood cell counts. There are also treatment-related factors, like the types of drugs, use of steroids, and how much prior treatment someone has had.
So, how do we try to prevent these infections? One key step is to control the myeloma, as less disease allows the immune system to recover. The second is prophylaxis—taking medication regularly to reduce risk. We can’t use it all the time in everyone; it must be targeted to when someone is most at risk. Third is immunoglobin replacement if antibody levels are low. And finally, vaccination is very important to strengthen our immune response.
[7:43] Regarding antibacterials (antibiotics) to prevent infection, older studies using drugs like trimethoprim-sulfamethoxazole (Bactrim) or fluoroquinolones (like ciprofloxacin) didn’t show much benefit. A later study with levofloxacin showed lower rates of fever, but no difference in long-term outcomes. A worrying downside of long-term antibiotic use is the development of bacterial resistance. Similar findings apply during stem cell transplant. So, routine antibacterial prophylaxis is not recommended for everyone, but it can be considered for individuals with recurrent infections. This is different from treating an active infection.
[11:11] For antivirals, we target specific viruses. Herpes simplex (cold sores) and herpes zoster (chickenpox/shingles) can reactivate. We use antivirals like valacyclovir to reduce this risk, especially after stem cell transplant (for up to 12 months) or during treatment with proteasome inhibitors like bortezomib or carfilzomib. For patients with a history of hepatitis B, preventative antivirals are also recommended.
For antifungals, they are used in specific situations. After stem cell transplant, when the immune system and neutrophil counts are very low, we might use an antifungal like posaconazole. When on high-dose steroids, we use trimethoprim-sulfamethoxazole to prevent Pneumocystis pneumonia.
[15:13] For the newer generation treatments like bispecifics and CAR T-cells, our infection data and recommendations are not as strong yet, as we are still learning.
Immunoglobulin replacement (IVIG or subcutaneously) is considered when antibody levels are very low, especially for patients who have had serious infections, as it can reduce the risk.
[17:31] Vaccinations are a passion area of mine and very important. Key recommendations include:
- Pneumococcal vaccine: A combination of Prevenar 13 followed by Pneumovax 23 at diagnosis.
- Influenza: The adjuvanted vaccine annually.
- COVID-19: Primary doses and boosters as recommended.
- Other: Meningococcal and Haemophilus vaccines are also important.
Some treatments, like lenalidomide, may not negatively impact vaccine response.
[20:54] After stem cell transplant, intense chemotherapy wipes out prior immunity, so a revaccination program is recommended. This includes a new, safer shingles vaccine called Shingrix (an inactivated vaccine). The older live vaccine, Zostavax, is not recommended. The full schedule is offered to patients post-transplant.
[22:37] Regarding COVID-19, for patients who may not respond well to vaccines, there were long-acting monoclonal antibody preventative treatments (like Evusheld). These were effective but are no longer recommended against current circulating strains. New options are in development.
[24:31] To summarize the layers of protection:
- Vaccination for eligible patients.
- Long-acting antibodies (if/when effective ones become available).
- Immunoglobulin replacement for those with low levels.
- Targeted antibiotic/antiviral prophylaxis in select situations.
- Vigilance: Do not ignore signs of infection like fever and chills. Early recognition and treatment are key.
[26:38] Nel: Thank you. You touched on a lot of topics I encounter as a myeloma nurse. I have some questions. The first is about COVID: Should people with myeloma still be isolating, or do you have a recommendation on when to stop?
Ben: It’s a tricky question. It depends on the phase of treatment. Some phases are more intensive. In general, indoor activities with crowds carry higher risk. I encourage a balance of living life but being careful—masking up in crowded indoor spaces is still wise. For specific situations, like starting intensive therapy, take advice from your clinical team on extra precautions.
[30:44] Nel: Another question on Evusheld: will another similar therapy be available soon?
Ben: The approach of long-acting antibodies as prevention is here to stay. New products are being developed and evaluated in clinical trials. We’ll have to see if they are effective against circulating strains.
Nel: Regarding the Shingrix vaccine: if someone receives the full course, do they still need to take antivirals like valacyclovir?
Ben: The quick answer is no, but it depends. After a stem cell transplant, once the Shingrix course is complete, you can stop valacyclovir. However, if you later start a proteasome inhibitor, teams might be more cautious and still recommend it, as we’re not sure if the vaccine alone is enough in that context.
Nel: Is there a specific wait time needed between different vaccines?
Ben: In general, most vaccines can be co-administered. It’s more important to maintain the recommended schedule. After a stem cell transplant, we can give up to four vaccines in one sitting. The schedule is the key, not a waiting period.
Nel: Thank you. You’ve done really well answering some curly questions that often require patient-specific answers.
Ben: No worries. I’ve tried to give broad advice. For your specific situation, always get advice from your clinicians. If they are uncertain, they can seek additional advice from infectious diseases specialists.
Nel: Definitely. Thank you so much for giving your time this morning and sharing so much with us.
[30:44] Thank you. Um you also as part of your talk you were talking about the Shingris vaccination which you mentioned is not PBS listed but there are people who um are receiving it and for people that have received um the full course of the Shining Greeks vaccination do they still need to keep taking their antivirals like Valtre?
Yeah, great question. Um the quick answer to that is no but also depending on the situation. So I’ll I’ll explain my my answer there in two parts. So if if for example if it’s after a stem cell transplant and you’ve completed the two doses of shingri then in that situation you don’t have to keep taking valley cycllovate. uh but why I’ve qualified my answer is just because in different scenarios where people have had shingri but then have had to go on to let’s say a another proteome inhibitor so more calfism or more botism then in that situation we’re not sure if shingri alone is enough to prevent shingles so then most in most I think clinical teams they would be more cautious and still recommend people take shing shingris in that situation. So, but if it’s after transplant and you’ve completed your course and let’s say you’re on rev limit as a maintenance, then you know you should be able to stop your valet cyclopia.
Thank you. Um is there a specific time frame that you need to wait between having different kinds of vaccines? So if you use Shingri for example, do you need to wait before you have another COVID booster or um or is there any other sort of time frames that you could talk to?
Yeah, so look in general um the vaccines themselves can be co-administered. So, so there are very few um of course again always check with with your providers for specific vaccines but in general most of the vaccines can be co-administered without you know needing a break between themselves but the as you can see from the previous slide I I’ve shown is that vaccine schedules are very complicated and they all are all sort of scheduled in a certain way. So it’s more important to maintain that schedule rather than sort of focus on you know whether they can be given together. But when if the schedule’s lined up like after stem cell transplant we can certainly give you know for example we we do u up to four vaccines in the same um sitting. So that shouldn’t be a problem. It’s just making sure that whatever vaccine you’re having fits its schedule.
Thank you. you’ve done really well at answering some kind of curly questions that are often requiring a specific answer on a patient to patient basis, but you’ve done really well. So, thank you very much.
No worries. I mean, I’ve tried to give as broad an advice at least. Of course, you know, when it comes to your specific situation, it’s always good to get a specific answer from your clinicians. And if they are not as certain, of course, they can seek additional advice from I’m sure there’s lots of equivalents of me across um uh different teams. So, so I think it’s always important to get specific advice if you’re not sure.
Definitely. Thank you so much for giving your time this morning and sharing so much with us.
