Safety and response rates with Abecma (idecabtagene vicleucel) were seen to vary with race in people with relapsed or refractory multiple myeloma (RRMM), but overall survival rates were similar between hard-to-treat Black, Hispanic, and white patients, a new U.S. study found.
“We see that Black and white patients with multiple myeloma both respond well to [Abecma],” Lauren C. Peres, PhD, one of the study’s co-first authors and an epidemiologist at Moffit Cancer Center, in Florida, said in a press release from the American Society of Hematology (ASH).
Minority patients, however, typically are less likely to receive these novel treatments — and to even be included in such clinical trials — the researchers noted.
“In fact, 75% of our study population would not have been eligible for the trial that led to [U.S.] approval of [Abecma],” Peres said, adding that this “lack of clinical trial representation can limit underrepresented groups’ access to life-saving care.”
“We hope that these findings encourage the use of [Abecma] in all patients with multiple myeloma,” Peres said.
The study, “Racial and ethnic differences in clinical outcomes among multiple myeloma patients treated with CAR T-cell therapy,” was published in the ASH journal Blood Advances.
Abecma designed for patients with hard-to-treat myeloma
Abecma, co-developed by Bristol Myers Squibb and 2seventy biowas approved in the U.S. in 2021 for treating adults with RRMM who have received at least four prior lines of therapy. Such treatments must include at least one immunomodulatory drugone proteasome inhibitorand one CD38 inhibitor.
A CAR T-cell therapyAbecma involves collecting an individual’s immune T-cells, engineering them in a lab to make them better at killing myeloma cells, and infusing them back to the patient. The modified cells are equipped with a chimeric antigen receptor, or CAR, that targets BCMA, a protein present at high levels on the surface of myeloma cells.
This type of cancer is more prevalent among Black and Hispanic populations than in white communities. However, minority patients “have a longer time from diagnosis to initiation of treatment, are underrepresented in clinical trials, and are less likely to receive novel therapies relative to non-Hispanic white patients,” the researchers wrote.
This is a glaring issue in the running of clinical trials, according to Peres.
“Clinical trials often lack diversity for many reasons such as recruitment barriers, financial considerations, medical mistrust, and cultural insensitivity,” Peres said, “but stringent trial eligibility criteria also often exclude racial and ethnic minorities.”
Now, Peres and colleagues sought to find out how clinical outcomes differed between racial and ethnic groups treated with Abecma.
To that end, they retrospectively analyzed data from 207 RRMS patients treated with Abecma at 11 institutions that participated in the U.S. Multiple Myeloma Immunotherapy Consortium. Patients were followed for a median of 9.3 months.
Specifically, the researchers monitored patients’ remission rates and overall survival, as well as safety complications.
Among the participants, 149 identified as non-Hispanic white (72%), 36 as non-Hispanic Black (17%), and 22 as Hispanic (11%) patients. The Hispanic and white patient groups had significantly more men (73% and 61%) than did that of Black individuals (42%).
Longer hospital stays, more complications seen for Black patients
Blood levels of C-reactive protein, a marker of inflammation, were examined. At the study’s start, these levels were significantly higher, by about threefold, among Black patients when compared with Hispanic and white individuals, the results showed.
Black patients also were more likely to develop cytokine release syndrome or CRS (97%) — a serious inflammatory reaction that can be triggered by CAR T-cell therapies — than were Hispanic (77%) and white patients (85%).
“This finding could potentially be explained by an elevated pro-inflammatory state among non-Hispanic Black patients prior to [Abecma] infusion, as studies show that patients with a [starting] pro-inflammatory response are more likely to develop CRS,” the team wrote.
However, race and ethnicity had no influence on the risk of developing severe CRS. These factors also had no effect on any grade of immune effector cell-associated neurotoxicity syndrome, a potentially life-threatening immune response affecting the brain that’s also a potential side effect of CAR T-cell therapy.
The use of steroids and tocilizumab —a commonly used anti-inflammatory medication — also were similar between the three groups. Hispanic patients were more likely to use Kineret (anakinra) to ease inflammation (14%) than were Black patients (0%) and white patients (5%), although these differences did not reach statistical significance.
Black patients had a significantly longer median hospital stay compared with white and Hispanic patients, with a median of 13.5 days versus 8-9 days. Intensive care unit admissions showed no significant differences by race or ethnicity, however.
No significant group differences were observed in terms of overall response rate (ORR) — the percentage of patients that achieved a partial, very good partial, or complete response — 30 days after treatment. But after 90 days, or about three months, the ORR was significantly lower in Hispanic patients (48%) relative to Black patients (66%) and white patients (76%).
When assessing the best ORR, Hispanic patients also had the lowest rates, specifically 59% versus 86% for both Black and white patients. This remained true even after considering multiple factors at the same time, with Hispanic patients being significantly more likely, by about seven times, to have an inferior response relative to white patients.
However, what that meant was unclear.
According to researchers, it could be due to the “small number of Hispanic patients in our study, unmeasured [influencing factor]or it could point to biologic differences across race and ethnicity.”
Results highlight need for more diversity in clinical trials, researchers say
While white patients seemed to live slightly longer without signs of disease progression, or progression-free survival, these group differences did not reach statistical significance. In all, white individuals lived 8.5 months versus 6.5 months for Black patients and 4.2 months for Hispanic patients.
There also were no significant group differences in terms of median overall survival. Indeed, this was not reached in any of the groups, meaning that most patients were still alive at the last follow-up.
Analyses adjusted for potential influencing factors also confirmed that race and ethnicity were not significantly associated with progression-free survival or overall survival.
Overall, “we observed differences in safety and response rates by race and ethnicity, but no differences in [progression-free survival] or [overall survival],” the team wrote.
Peres said the results “highlight the need for diverse patient [groups] in research and clinical trials.”
The researchers called for future larger and more racially-diverse studies that follow patients for a longer time period.
“Continued evaluation of safety and efficacy across diverse patients is critical to ensure equity in the improvement of outcomes for all RRMM patients,” the researchers concluded.
