Targeting BCMA With Teclistamab Produces Impactful Results in RRMM

CASE

• A 63-year-old man from a rural community was diagnosed 8 years ago with multiple myeloma (IgG-κ)​.
• Recently, he presented with penta-refractory disease progression (4 prior lines of therapy that included autologous stem cell transplant (ASCT), 2 proteasome inhibitors, 2 Immunomodulatory agents (IMiDs), and 1 anti-CD38 antibody drug).
• Medical history includes hypertension controlled with lisinopril​.
• ECOG performance status: 1
• The patient asked about chimeric antigen receptor CAR T-cell therapy, but after counseling, opted to pursue an alternative therapeutic due to length of waiting lists at accessible institutions.

Targeted Oncology: What was the makeup of the MajesTEC-1 study (NCT03145181) and how does this stand out in the current landscape for treatment of patients with relapsed/refractory multiple myeloma (RRMM)?

Ailawadhi: About a quarter of the patients [on the trial who were given teclistamab (Tecvayli)] were above the age of 75 years old.1 Seventeen percent of patients had 1 or more extramedullary plasmacytomas, with about 15% [of those patients being] older than 75 years of age. Patients who were triple-class or penta-drug refractory made up decent numbers [on the study at 77.6% and 30.3% of patients, respectively]. As we're looking at more and more drugs that are coming down the pike, I think this extramedullary factor is becoming more important. This is because, even when we were [mostly giving] carfilzomib [Kyprolis], daratumumab [Darzalex], etc, we were noticing that patients who were relapsing after a lot of these agents was because more plasmacytomas are seen when their survival is longer.

Sikander Ailawadhi, MD​

Associate Professor

Mayo Clinic​

Jacksonville, FL

In fact, some of the newer trials for drugs are targeting, or allowing, patients in their trials with non-secretory disease, which is measured only on PET scans for plasmacytomas. I'd also add that [in the studies for] a couple of the drugs that are in development right now, they've gone to a lot of lengths to define exactly what is an extramedullary disease, and clearly defining bone-based plasmacytomas or soft tissue plasmacytomas to see where their drug is effective. Otherwise, there can be a mistake with a bone-based plasmacytoma counted as an extramedullary tumor.

How has clonal evolution impacted these patients with RRMM on several or more lines of therapy?

It's almost that the clone that is emerging is [now] behaving differently. Clonal evolution used to be seen in a smaller number of patients before and now we see it much more frequently.² [One reason is] because of the length of survival of patients since they're living longer with these drugs. Second, the change in altered biology of the disease, or what is it's exposed to, and what emerges from treatment. When I was doing my fellowship, my mentor told me there was this very interesting case admitted at the hospital, the patient has multiple plasmacytomas and said I should follow this case because I may never see this kind of a case again. A week later, there was a second patient [with multiple plasmacytomas], and my mentor was sure we wouldn't see this kind of a case again, but clearly that's not the reality anymore.

[In relation to the RRMM population on this study], this was a very heavily pretreated patient population…. Ninety percent of patients were refractory to the last line of their treatment,1 meaning they were progressing either on treatment or within 60 days of stopping treatment. While in the International Myeloma Working Group criteria, refractory [can still be defined as] progressing within 60 days of stopping treatment, in these patients who are on so many lines of therapy it's generally while on treatment they progress and are now refractory.³

What was the efficacy of teclistamab for the patients on this study?

Nearly 40% of patients achieved a stringent complete response [sCR] and about 20% of patients had a very good partial response, so [these patients saw] a more than 90% reduction in their disease.¹ [Just 4.2% of patients] had a...partial response; altogether, the overall response rate [ORR] was about 63%. So, two thirds of patients who were heavily pretreated responded [to teclistamab] with a big chunk of patients having a CR, and I think that's one of the reasons every time one of these [bispecific] drugs comes out it makes it directly to a New England Journal of Medicine paper, because it's way better than where the precedent is at.

The median overall survival was about 18 months, but [the data] had not matured at the time of this data cut off.1 Median progression-free survival was [at 11.3 months] with a long median duration of response at 18.4 months, [but the duration of response was also not mature]. The ORR was consistent across [subgroups of patients like those with] high cytogenetic risk or patients who were penta-drug refractory.¹ I think in all our clinics, [these data] go towards the efficacy of B-cell maturation antigen [BCMA] being the standard-of-care target. We've seen similar results with other therapies targeting BCMA, and in my opinion, targeting BCMA must be considered a standard for every single patient with myeloma.

^References:

^{1. Moreau P, Garfall A, van de Donk N, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med.2022; 387:495-505. doi:10.1056/NEJMoa2203478}

^{2. Salomon-Perzyński A, Jamroziak K, Głodkowska-Mrówka E. Clonal evolution of multiple myeloma-clinical and diagnostic implications. Diagnostics (Basel). 2021;11(9):1534. doi:10.3390/diagnostics11091534}

^{3. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014;15(12):e538-48. doi:10.1016/S1470-2045(14)70442-5}