Optimization of Therapies for Older or More Frail Patients With Multiple Myeloma

At the 2023 Great Debates & Updates in Hematologic Malignancies conference in New York, New York, Joshua Richter, MD, Mount Sinai, New York, New York, discussed the optimization of therapies for older and more frail patients with multiple myeloma (MM). 

Transcript: 

Hello, my name is Dr. Joshua Richter. I'm an associate professor of medicine at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, and the Director of Myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai. 

I'm here today to recap a presentation I gave [at] Great Debates and Updates in Hematologic Malignancies. My talk focused on optimizing myeloma therapies for older and more frail patients. 

Although myeloma can affect a variety of different patients in different ethnic groups, it tends to affect patients who are a bit older in general. The average age of diagnosis in the United States is 69 years of age, which means many of our patients are 70 or older, have multiple comorbidities, and may, in fact, be more frail from a number of standpoints. I focused on several areas of this. One is first establishing who is frail and how we go about doing this.

There are a number of ways, and we've actually studied the fact that frailty is not just a number. We all have those 80-year-old patients who are running marathons and younger patients who may be more frail for a variety of reasons. So, assessment of frailties and geriatric assessments are key to identifying who may need alterations in their therapeutic approaches. There's a lot of different ways of assessing frailty. You can use some of the geriatric assessments that have been used, including grip strength and the 4-second walk test. The International Myeloma Working Group and a variety of other groups have developed these different programs to assess frailty using things like the Charleston Comorbidity Index.

The other thing that we talk about is social frailty. This is a fairly new concept, really understanding that patients who have social frailty, patients that may not be able to get back and forth to their appointments. This may impact things quite a bit.

The first step is establishing who is truly frail. One of the things that I brought up is that if you look at all the current approvals for therapies in the United States for myeloma, there's no difference in the approvals for patients who are older or frailer. Essentially, we can give all of the same therapies, we just have to dose adjust as needed and provide appropriate supportive care. 

Dose adjustment can come in a variety of ways. It can be lowering the milligram dosage, but could also be extending out the frequencies. Instead of giving a therapy twice in a week, maybe giving therapy once a week or once every other week. So not just dose reductions, but those are important as well. Dose-reducing drugs like lenalidomide from 25 milligrams down to 10 or 15. Perhaps one of the biggest dose adjustments we should do in myeloma is dexamethasone. Instead of giving 40 milligrams once a week, give 20 or even 12 or even less. 

I presented some great work that was done by LaRocca and colleagues about dropping the dose of dexamethasone long-term to improve tolerability and ultimately improve efficacy. We talked about a number of therapy approaches in the upfront setting, which includes the MAIA study, giving things like daratumumab LenDex upfront. Although a lot of patients go on to receive just lenalidomide alone, the TOURMALINE MM6 study showed us that for patients where we continue lenalidomide LenDex plus ixazomib, for patients who receive the bortezomib induction can have an improvement in their depth of response and tolerate things well overall. Ultimately, for patients that we don't feel will do well enough with lenalidomide alone, we can use [ixazomib, lenalidomide, and dexamethasone] (IRD).

When it comes to transplantation, we still recognize that transplant represents a key approach and including patients over the age of 70. It turns out that giving the full ml 200 is probably better than the 140. So, don't just dose produce your melphalan based on age.

Once we get to the relapsed/refractory setting, there's been some wonderful frailty analysis in the IKEMA and IKARIA trials looking at giving ESA-PD and ESA-KD in patients who are more frail and there was no difference in the frail or not frail. These represent great options. Therapies such as selinexor, velcade, dexamethasone, based on the Boston trial, showed improvement in patients who were frail and or over the age of 65 with the triplet of XVD over VD and considering some oral combinations such as pomalidomide, cyclophosphamide, dexamethasone are great all oral combinations for older, frailer patients.

The 2 big things we still are talking about very deeply in myeloma is the T-cell redirection therapies. Bispecific antibodies are becoming a very hot topic in myeloma, and perhaps incorporating prophylactic strategies such as prophylactic tocilizumab prior to dosing your bispecific may reduce the incidence and grade of [cytokine release syndrome] (CRS), making it more tolerable for older or frail patients.

And we're still evaluating [chimeric immunoreceptor] (CAR) T therapy in patients over the age of 70. There have been a number of studies looking at this and it's something we can start doing, especially if we provide aggressive risk stratification, geriatric assessment, and prophylactic techniques.

In summary, patients over the age of 70 represent a large portion of our myeloma patients, and many of them may have further frailty above and beyond age alone. It's really important to this and giving basically comprehensive therapy, comprehensive assessments, and providing similar regimens we do to non-frail and or younger patients. Taking extra steps to re-stratify, dose adjust, schedule adjust and assess things including social frailty to provide optimal therapy for the select group of patients. Thank you.

Source: 

Richter, J. Optimizing myeloma therapies for older and more frail patients. Presented at Great Debates & Updates in Hematologic Malignancies Conference; April 13-15, 2023; New York, NY.