On Saturday, March 15,  IMF Chief Medical Officer Joseph Mikhael MD, MEd, FRCPC, FACP, FASCO, along with IMF Vice President of Development Sylvia Dsouza, hosted a Facebook Live Q&A session in Boca Raton, FL to answer the most pressing questions about myeloma care, myeloma research, and more as part of Myeloma Action Month.

 

Dr. Mikhael began the Q&A session by talking about the highlights of the Patient and Family Seminar that was currently ongoing in Boca Raton at that time.  

“What is really hot in myeloma that is so new I can't even create slides for it because it's so brand new? Very quickly, I talked about two things—a critical trial that was recently conducted and published, the AQUILA trial, that was looking at treating patients with high-risk smoldering multiple myeloma that is really sending some shock waves into the myeloma community about how we may be able to intervene earlier in myeloma. One of the great objectives we have at the IMF is to facilitate an early and accurate diagnosis so that people can be caught before their bones break, before their kidneys are damaged. And this study was a part of that strategy and showed that single agent Darzalex or Daratumumab may have a prolific impact in this area,” said Dr. Mikhael. 

“Area number two was what we call Down with Dex. We know that dexamethasone is important and it's a part of just about every chemotherapy regimen on the planet. Years ago, when we didn't have a lot of great drugs, we really relied on dexamethasone. But now, we can rely less on it, and we've seen recent publications and really excellent work helping us see that we can reduce the dexamethasone. And as a patient or as a care partner, you probably know what this is like, that although we love dex because it helps those chemo regimens, we kind of hate dex too because it causes a lot of side effects, difficulty sleeping, it affects our mood, blood pressure, blood sugar, so many other things. And we think we can live in a world with much less dex,” he continued. 

Here are some of the top questions and answers that we gathered from this informative and insightful Facebook LIVE session. (EDITOR’S NOTE: Viewers’ questions and Dr. Mikhael’s responses have been edited for conciseness and clarity):   

 

1. What are the latest treatment options and strategies after stem cell transplant and CAR T-cell therapy?  

Autologous stem cell transplant (ASCT) has been a centerpiece of treatment for transplant-eligible myeloma patients. Could it be that CAR T-cell therapy is going to come earlier on? Clinical trials are being done, and we anticipate that may happen. But of course, we need to see the evidence for it.  

Be assured that there is a lot after CAR T-cell therapy. In fact, Dr. Krina Patel of MD Anderson Cancer Center was just talking about her experience of giving bispecific antibodies after CAR T-cell therapy and how effective that can be. Not only so, we have another wave of CAR T and bispecific antibodies that are being developed, sort of the CAR T 202 and bispecifics 202.  

And even yet, other molecules, cell mods and newer targets that we use in multiple myeloma. So, although we think of a major step forward with CAR T, there are many more steps coming. 

 

2. Can Darzalex Faspro be used effectively as maintenance therapy without Revlimid? 

For a long time, we've been giving Revlimid® (lenalidomide) maintenance. We use the word “maintenance” typically, after someone has had an autologous stem cell transplant to maintain their remission, achieved by that initial therapy and transplant. For many years, we've used Revlimid alone because it clearly showed not just long-term remission but long-term survival as well. 

Now, we’re doing more studies and evaluating the opportunity to add another drug to it. Sometimes, we may add Velcade® (bortezomib) or even Kyprolis® (carfilzomib) to it, but there's been increasing evidence that adding Darzalex® (daratumumab) keeps patients in remission for longer— a legitimate strategy. 

However, the question is if we can use Darzalex alone. Although we don't have a lot of studies, we do have a few that have evaluated this. We know that Darzalex alone is absolutely better than nothing. We also know that there are about a third of patients who, for various reasons, can't stay on Revlimid because of side effects or other issues. And often, we maintain those patients on Darzalex and we're getting a lot more experience with it.  

Yes, it is a legitimate option but needs to be discussed with your provider because every patient is unique and different. It is a strategy that we're often using, and we typically combine it with something else. But if that something else (like Revlimid) has to be dropped, we often do use Darzalex alone. 

 

3. Is it beneficial to restart maintenance therapy after a six-month break for ultra high-risk myeloma?
 

Typically, we continue maintenance until someone's disease wakes up. That's the general strategy. But sometimes, we must stop due to side effects or other reasons. Those with lower risk myeloma or those who have been on maintenance therapy for maybe over 4-5 years may decide to stop treatment. 

However, when someone has ultra high-risk myeloma, the disease has a greater ability to come back more quickly. We typically try not to keep patients off maintenance therapy for too long.  

Generally speaking, if there has been no relapse for six months, we would go back to maintenance with two drugs. Of course, every patient is different. There may be some situations where a patient may not be given anything while keeping a close eye if the myeloma re-emerges, because ultra high-risk myeloma tends to come back. However, there may be exceptions to the rule.  

For example, I had patients who have high-risk myeloma and actually stayed off maintenance for a considerable time but had long-term remission. That is up for discussion, but the short answer is typically, we prefer high-risk myeloma patients to be on continuous therapy. 

 

4. How does Kyprolis (carfilzomib) compare to Velcade (bortezomib) in terms of effectiveness and side effects (especially peripheral neuropathy and heart issues)?  

Velcade (bortezomib) and Kyprolis (carfilzomib) are part of a family of drugs called proteasome inhibitors. They’ve been around for many years, with both very effective, and very much incorporated into treatments. Velcade and Kyprolis work similarly, but each drug has its own set of side effects. 

Velcade can cause peripheral neuropathy—numbness, tingling, maybe even pain in the fingertips or the soles of your feet. When that happens, it is an important consideration, and we typically stop treatment. 

Sometimes, we may not replace Velcade with something else. But if someone requires ongoing treatment with that proteasome inhibitor class, there are a few other options: Ninlaro® (ixazomib), or Kyprolis. 

Kyprolis is a very potent drug in this class, and I use it regularly in my practice or clinic albeit needing to be used carefully. Patients may experience side effects from Kyprolis but I would say that they occur in only about 5 percent or less of patients. 

However, one of those issues can affect the heart. Also, there have been reports of Kyprolis increasing blood pressure. If a patient has pre-existing heart failure, the drug can slightly worsen it.  

We learned over time that when started at a lower dose and given once weekly, a vast majority of patients can keep staying on Kyprolis without much complication. We closely monitor patients’ blood pressure and cardiac status, of course.  

 

5. What strategies can be used to prevent or manage weight gain caused by dexamethasone?
 

As I noted earlier, dexamethasone is a drug we both love and hate. It boosts the effect of just about every treatment— giving patients energy, alleviating nausea and pain, and helping reduce potential side effects from chemotherapy, infusion, or administration reaction.  

However, over time, dexamethasone can cause a lot of other side effects. It can stimulate appetite, causing patients to retain fluid and gain weight. There is no perfect antidote to it. As I have commented with the Down with Dex movement, can we start looking at tapering down the dose? 

Typically, patients start with either 20 or 40 milligrams weekly. With the Down with Dex studies, we found that if we can use that for the first month or two, that’s where the greatest benefit is, and then often we can start tapering it. Based on our experience, we can start reducing the dose by the second month. Often, patients can completely discontinue dexamethasone by the fifth or sixth month. 

That can help with preventing weight gain, or if patients gained weight during the course of the treatment, they are able to shed off some of that weight when they come off dex. I would recommend discussing the option of tapering down dex with your doctor. 

I would strongly encourage discussing this in-depth with your doctor and medical team. But if you experience peripheral neuropathy while taking Velcade, I recommend stopping treatment, as it will only worsen the neuropathy. 

 

6. Is it common for patients in remission to still experience bone pain, and what could be the cause?

When we talk about remission in myeloma, we refer to the fact that we've controlled and reduced the burden of disease. Myeloma is always complicated. It may be the M spike, the light chain.  X-rays are important, as well as the bone marrow and blood work. Sometimes we do PET scans and things like that. In general, remission means less pain, less fatigue, and less discomfort. 

However, when it comes to bone damage, it is possible that myeloma is the cause; some of it can remain permanent. It’s a very important discussion with your healthcare team, to decipher whether the pain is a sign of myeloma re-emerging, or if the myeloma is not fully controlled. 

Could it be permanent bone damage? If a patient broke a bone because of myeloma, we could give them a bone strengthening drug. Often, the pain will be alleviated, and the integrity of the bone will improve. However, there may still be some residual pain. It is important to discuss the type of pain and its intensity with your healthcare team.

 

7. What remedies are being explored to address T-cell fatigue after CAR-T therapy? 

For those who are not familiar with T-cell therapy, T-cells are a form of white blood cell that help fight off infection. We have developed multiple ways of engaging T-cells. T-cells are taken from the patient and trained to recognize the myeloma through receptors. These engineered T-cells are called chimeric antigen receptor T-cells (thus, CAR T), and they are re-introduced to a patient’s system through an infusion.  

Sometimes, patients are given a bispecific antibody or a drug that hooks on to a myeloma cell and a local T-cell to engage the T-cell to attack the myeloma cell.  

These therapies are incredibly effective—we’re seeing responses and duration of responses that have never been seen before in myeloma. Still, the reality is that they are not perfect and over time, can become less effective. These T-cells can eventually run out of steam.  

Is it possible to re-invigorate the T-cells with another drug? This is still being carefully evaluated in a great area of research. For now, when a patient relapses after a CAR T/bispecific therapy, we need to look into another form of treatment. The good news is, we can go back to another CAR T or bispecific later on.  

 

8. How might potential research funding cuts affect myeloma research and clinical trials?  

I would approach this in such a way that it reminds us of the importance of myeloma research. More than ever, we are getting closer to a cure for myeloma, and we want to support research that is being done by institutions across the globe.  

At the IMF, we serve a critical role in facilitating a lot of that research, in particular through the International Myeloma Working Group (IMWG), which is comprised of 350 myeloma experts from around the world. 

We are concerned about the threat of funding cuts. One of the IMF’s pillars is advocacy—we invite you to join us in reaching out and advocating to our elected officials on the importance of research and clinical trials for myeloma patients. 

We are hoping that with the tireless support of the myeloma community, these research endeavors will continue, up until we find a cure for myeloma. 

 

9. What is the risk of developing secondary hematological malignancies during the smoldering phase of myeloma? 

During the smoldering phase of myeloma, we have less evidence of that exact number, but we do know that if you look at a myeloma patient on average, over the course of their life, they'll have about a 5 percent risk of developing another cancer.  

There are a lot of reasons for that. It may be that their inherent genetics puts them at risk, or some of the treatment that they've had or what I call the incidentaloma, the fact that they are being able to be tested and be looked for. 

So, it's important that patients get regular screenings: colonoscopies, mammograms, those kinds of tests. We're still trying to understand the exact incidence and ways in which we can reduce it.  

 

In closing, Sylvia thanked Dr. Mikhael and emphasized how the IMF is still at the forefront of the battle, doing a lot of work to fulfill its mission of finding a cure for myeloma. She invited everyone in the myeloma community to stay engaged, actively participate in IMF events, and reach out to the IMF if they need any assistance or if they want to be involved in the IMF’s initiatives. 

In case you missed it, you can still watch a replay of the Facebook Live Q&A in its entirety.