How can induction therapy be modified for frail or transplant ineligible patients?

Starting treatment for multiple myeloma can feel overwhelming, but it's important to know that you are not alone. Treatment is a personalized journey, often involving a combination of medications. Your care team will tailor a plan based on overall health and features of your myeloma. Ask your doctor about treatment options. Possible side effects and how this might affect your day to day life.

In this Health Treat University lesson, you'll learn what myeloma specialists consider to be an appropriate treatment path. If you are considered to be frail, how can induction therapy be modified for frail or transplant ineligible patients?

frailty in myeloma patients. You know, as we know that myeloma is a disease of the elderly with a median age of 69 years.

Many of our patients, when they first present, get diagnosed with myeloma. They're not just old, but they also have organ dysfunction.

They have poor physical health. And oftentimes they are considered ineligible for clinical trials.

And these patients still, I believe, can go through chemotherapy, modified, to make it better tolerable for those patients, In my practice, typically, if I have patients who are frail and cannot go through intense treatment, including transplant. I would still consider giving them chemotherapy.

I would give them 3 or 4 drugs combined together, but given in a very modified, dosing and frequency, pattern that is very well tolerated by the patients. And we have seen over the period of time, not just from clinical trials, but also from real world evidence that these patients, when they are offered a chance with chemotherapy, modified, abbreviated for better tolerance, still live a long life.

So, the outcomes in myeloma care are not just getting better for the fitter, younger, transplant eligible patients, but also the ones with older, frail and perhaps transplant deferred. So chemotherapy on that front, I think has there have been some tremendous strides in the chemotherapy, limb for those patients.

What types of anti myeloma therapy do you consider using in the frail population?

when we look at, three drugs or four combinations, you know, we are incorporating increasingly incorporating, cd38 antibodies, which can be given, as an injection under the skin, very effective and extremely well tolerated with no major side effects.

We are still using, proteasome inhibitors, mostly the first generation as injections. And again, when you give it them less frequently, perhaps once a week, instead of twice weekly that they're really to peripheral neuropathy and other associated side effects.

And finally, when you look at, immunomodulatory agents, like therapies that have been out there for a long time, the lenalidomide, when you dose adjust, the lenalidomide from a high dose to a lower dose actually is fairly well tolerated by patients.

What we have learned, really learned over the last couple of years is about dexamethasone is perhaps the biggest evil, you know, with elderly, frail patients.

They have significant side effects from corticosteroids, dexamethasone.

And recently, published literature shows us that you don't really need to give patients dexamethasone beyond a couple of months. And they still, continue to respond, respond well, and be spared of all the toxicities of, steroids, these regimens have actually really, revolutionized the outcomes, in myeloma, especially frail patients.

When do you switch from combination treatment to maintenance therapy?

typically we would do induction period with four drug combination or three drug combination for at least six months. At the end of six months mark, if we think that a patient is responding exceptionally well, we can deescalate to three drugs or two drugs for that matter, with CD38 antibody and drugs like, lenalidomide. But six months is adequate enough duration.

We do actually see these responses, deep and durable responses at a good transition point.

There are times when we maybe stretch it out by a few more months to get to a deeper response before deescalating from four drugs to two drugs. And then there are times when patients respond especially exceptionally well to a couple of, cycles of chemotherapy, and we feel like we need to give them the better quality of life with fewer drugs.

And that's also not outside, the realm of possibilities for these patients, but typically six months.

When transitioning to maintenance therapy, how do you decide whether to de-escalate to 1 or 2 drugs?

typically if the standard risk myeloma patients do not have bad cytogenetics or mutations, giving them two drug combination with CD38 antibody once a month and then dose adjusted, dose modified. Lenalidomide actually works very well. These responses can last as long as 5 to 7 years, sometimes for patients. Patients who have high risk myeloma, which again is good 15 to 20% of all myeloma at the time of diagnosis.

It's not entirely clear whether the combination of CD38 antibody with, lenalidomide is appropriate versus maybe giving them lemalidomide in combination with bortezomib. I usually discuss this with my patients. And I asked them what their preference and the side effects, if a patient has a strong preference to receive once a month.

Injection with a visit and they do have some neuropathy, then I my preference remains giving them CD38 antibody with lenalidomide. If the patient does believe that they want to get the best possible care. Adding bortezomib into this mixture, is not something, this something that I've tried in the, in the past as well for those patients.

If you're diagnosed as frail, does that mean you'll always be frail?

according to some estimates, 20 to 30% of myeloma patients when they first present are frail and they may not be frail by virtue of their age or their medical conditions, but just by the fact that they have, a cancer that has actually taken over their body has affected organ function, kidneys, bones, affecting the physical performance.

And hence they can be frail just by the virtue of having myeloma. As we begin to treat myeloma in these patients and the organ function starts improving, kidneys start getting better, boost on healing.

You actually do tend to notice significant improvement in the physical fitness and, and the frailty where patients who are unable to walk. Well, who are actually in a wheelchair bound or actually able to walk on level ground and finally start doing general exercise and participate in activities of daily life independent of any support.

Would you recommend physical therapy?

as early as the time of diagnosis, not all patients may be able to participate, in physical therapy, but it's very aggressively to be able to go through all of the physical therapy needed.

But having some form of activity with other physical or occupational therapy is the cornerstone of myeloma care for frail patients.

That can be in the form of working with the physical therapy three times a week. That can be the form of, going to a gym, doing some gentle exercises, long distance walking. And that can be also yoga and, swimming, which are really good for building core stamina and, resilience as patients go through their cancer treatment.

What other ways do you try to improve performance in the frail patient?

identify as patient as frail or non frail at the time of their diagnosis is a very comprehensive assessment that we do.

That is has actually been validated by the International Myeloma Working Group.

Once patient has been identified as frail, we do optimize their frailty by making different referrals to integrative medicine, including refer them to a physical therapist, occupational therapist to help with physical debility, patients who are having nutritional deficiencies or malnutrition, for that matter, at the time of diagnosis.

We refer them to a dietitian and then patients who have other medical comorbidities, including diabetes or renal dysfunction. We actually refer them to a diabetes educator. We educate them on how they can optimize their kidney function. And then finally, patients who, actually have some degree of cognitive impairment as our normal process of aging, which can be accelerated by myeloma.

We actually refer them to a neuropsychologist for comprehensive testing. And if you do think that there is some, neuro cognitive decline, we can actually help prescribe some exercises, mental activities that can actually help to keep them sharp.

So this particular protocol not only identifies frailty, but also intervenes. And then we have assessments performed at regular intervals every 3 to 6 months to see if the frailty scores are improving.

And we're trying to incorporate that now into a particular trial where we are, giving patients, chemotherapy at an abbreviated schedule, modified dosing frequency, so that we are not only targeting myeloma with an abbreviated yet effective chemotherapy, but also optimizing frailty with all of these interventions that we are doing. So I'm really excited about that particular research, because I still think that our frail patients, oftentimes are not candidate for trials yet if they are offered appropriate therapy, careful therapy can reap the benefits of all the advances we have made in the field of myeloma.

We learned that Doctor Hashmi has had a personal experience related to frailty and myeloma, and he wanted to share his story on why he started working in the frailty space.

My mom got diagnosed with myeloma about two years ago, and I was a myeloma specialist by that time. I was in South Carolina, I was actually leading the program with myeloma. And it's kind of serendipitous how, the diagnosis transpired that I usually receive communication from my friends, my family, my brothers. And one of these days, I got a WhatsApp message that actually had a patient, it's patient history and labs in there.

And I looked at it and I glance and I said, it looks like myeloma. So responded back to them saying, in those myeloma, I should be getting chemotherapy as an opinion or a suggestion, only to go back to their message, five minutes later and find that the name of the patient on that message was my own very own mother.

And I realized that, she wasn't doing well with it. She had renal failure. She was very severely anemic. She needed immediate therapy and treatment, which, again, as a dutiful son, I took over and, unfortunately, with all of my expertise, all my goodwill, when we started treatment, she had some difficulties, some reactions, side effects, toxicity.

So we have to scale back a little bit. It all ended well. All is well, that ends well. But, she's still going through Myeloma treatment. And, you know, I hear about her journey, her experience, the side effects that my patients used to tell me all these years now. And when she complains about them and I try to explain them to the best of my ability.

We have finally come to terms with the fact that this is, as of now, an incurable cancer, where the chemo has to be continued for a considerable period of time. But I have learned so much as a caregiver with that experience that being on the other side, the receiving end, you know, when you meet physicians, when you meet, healthcare providers, nurse practitioners, nurses in a hospital who take care of you, spend more time with you than anyone else.

You begin to realize the value of what these healthcare heroes are doing. So, I don't think I would have had that perspective, this early in my career if it had not been my own mother getting diagnosed with cancer and getting treatment in the hospital.

Because, you know, my own mother, I didn't find her as a myeloma specialist to be a transplant candidate because of frailty, the weakness, the physical debility And I realized that, you know, you need to improve outcomes in these patients as well.

I remember just that I prescribed physical therapy, but when my mother got diagnosed and she had to go through it, I participated with her. So I learned all of the physical therapy maneuvers, occupational therapy, measures that I could do on my own to help her regain her, health and how critical that can be in actually getting you stronger.

Oftentimes, as physicians, we may not have enough time or interest in learning about all of those things, but they are pivotal to actually optimizing outcomes with this cancer.

so far, she's doing very well. And hopefully you will continue to do so. But, you know, it affects your entire perspective and outlook on what you're doing for a living.

Thanks to Doctor Hashmi for sharing his story about his mother and for helping advance research for frail myeloma patients. And thank you for watching HealthTree University.