Tailoring Regimens for Different Age Groups With Multiple Myeloma

Andrew Yee, MD

Clinical Director

Center for Multiple Myeloma

Mass General Brigham

Massachusetts General Hospital

Assistant Professor of Medicine

Harvard Medical School

Boston, MA

Targeted Oncology: Why is achieving a quicker response particularly important for younger transplant candidates with multiple myeloma?

Andrew Yee, MD: From a practical perspective, for younger patients who are candidates for transplant, it is quite important to achieve a quicker response. [For example], using weekly doses rather than a single 25-mg dose might be beneficial, even for younger patients, with "younger" being defined as around 65 years old.

What are the key considerations when treating older patients with multiple myeloma?

For older patients, 70 years or older...[the approach may differ]. Certain colleagues might think about the ability to transplant, but for older patients…I would recommend using lenalidomide [Revlimid] 50 mg with CD30 antibodies. It could be a daratumumab [Darzalex] or another agent. My regimen would be 50 mg once a week for 3 weeks, with 1 week off. Studies like PERSEUS [NCT03710603]1 and IMROZ [NCT03319667]2 do not always reflect what I would do in clinical practice.

How do treatment strategies differ for younger, fit patients, and what is your approach to maintenance therapy after transplant?

For younger patients, say somebody under 60 who is fit, I would use more carfilzomib [Kyprolis]. Post-transplant, I would continue maintenance with the CD30 antibody plus lenalidomide, but at a lower dose of 10 or 15 mg for about 2 years. I would think about stopping but some patients continue beyond this if they are not complaining about it.

What factors influence your decision to use chimeric antigen receptor (CAR) T-cell therapy? What evidence supports its efficacy?

Regarding CAR T-cell therapy, if they had 4 prior lines, I would lean towards using CAR T first because there is some data suggesting that using a bispecific antibody before CAR T might compromise the efficacy of the CAR T therapy. This is based on a small number of patients who received idecabtagene vicleucel [ide-cel, Abecma] and ciltacabtagene autoleucel [cilta-cel; Carvykti]l. They experienced a progression-free survival for about 6 to 7 months with cilta-cel for example.

The [appeal of CAR T] is its potential for a one-and-done approach...which can be transformational for [patients who have been in therapy for years]. The improvement in quality-of-life can be great. When patients come to see us, driving an hour or more, they want to come in for that chance.

How do you decide between using CAR T-cell therapy and bispecific antibodies?

For us, we have mainly used the bispecifics post CAR T because CAR T does not work for everybody. Some patients relapse, so I have been using more bispecifics. I do have patients who are getting bispecific for whatever reason, and because I think CAR T can be logistically challenging. Then you have some patients who do not have the caregiver around, or maybe there are some niche patients where they have kidney dysfunction… and for those patients where they are relapsing, the bispecifics can work really well. But the bispecific antibody response is not as high as CAR T. The fact that the CAR T can give you that 1 and done option and when it does work, it is amazing, so I think a lot of patients gravitate towards that.

What are the emerging trends in bispecific antibodies, and what challenges do they present in clinical practice?

The space is getting more complicated as you have these new bispecifics that could potentially [offer improvements in] PFS better than what we already have out there. For example, there is also talquetamab [Talvey], which is a GPRC5D-targeting bispecific antibody. Talquetamab can be harder to give because there is not so much the rash issue, but dysgeusia is the main limiting factor.

REFERENCES:

1. Sonneveld P, Dimopoulos MA, Boccadoro M, et al. Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2024;390(4):301-313. doi:10.1056/NEJMoa2312054

2. Facon T, Dimopoulos MA, Leleu XP, et al. Isatuximab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. Published online June 3, 2024. doi:10.1056/NEJMoa2400712