Idecabtagene vicleucel (ide-cel) is a chimeric antigen receptor T cell (CAR-T) immunotherapy that targets B cell maturation antigens (BCMA) and has been approved in the United States in 2021 for patients with relapsed/refractory multiple myeloma (RRMM) who have previously received ≥4-line therapy. Although CAR-T cell therapy is effective, it can lead to severe toxic side effects when it exerts antitumor effects, common ones including cytokine release syndrome (CRS), immuno-effector cell-associated neurotoxic syndrome (ICANS), and infection. Older patients are at higher risk of infection than younger patients, and the management of CRS and ICANS in older patients is more complex due to comorbidities. So what is the efficacy and safety of ide-cel in the real world and in the elderly RRMM patient population? Two studies have been explored and selected for the oral report of the 2022 IMS Annual Meeting, and the main contents are summarized as follows.
01 [OAB-004] Ide-cel for RRMM patients: a real-world study
Researchers from the United States conducted a real-world study that retrospectively analyzed data from RRMM patients who received ide-cel treatment at 11 centers in the United States. As of February 28, 2022, 196 patients have completed leukocyte monometry and are planned for ide-cel treatment. In the end, 159 patients successfully received infusions and were included in this study for retrospective analysis (Figure 1).
Figure 1
Of these, 47% had extramedullary disease and 44% had pentatremic MM, both higher than the KarMMa trial (a key ide-cel trial) (Table 1). 77% of patients did not meet the admission criteria for the KarMMa trial (46% did not meet the >1 KarMMa trial admission criteria) (Table 2).
Table 1
Table 2
Ide-cel was similarly toxic in this study to the KarMMa trial, with CRS in 82% of patients and neurotoxicity in 18% of patients (Table 3). In addition, 34% of patients develop infections.
Table 3
On day 90, the optimal overall response rate (ORR) for 141 patients was 86 percent and the ≥ complete response (CR) rate was 42 percent. As of the data deadline, 13% (n=21) of patients had died. Thirteen died from disease progression and 8 from other causes. Median follow-up was 5.3 months, median progression-free survival (PFS) was 8.9 months, and median overall survival (OS) was not reached (Figure 2).
Figure 2
The results of the multivariate analysis showed that patients who had previously received BCMA targeted therapy and high-risk cytogenetic characteristics had shorter PFS (Figure 3).
Figure 3
The above results show that even if most patients do not meet the KarMMa trial enrollment criteria, the safety and efficacy of ide-cel standard therapy in real-world RRMM patients is comparable to that of the Phase II KarMMa trial. Previous bcMA-targeted therapy and high-risk cytogenetic features are independent predictors of poor prognosis in patients with RRMM treated with ide-cel.
02 【OAB-008】 Efficacy and safety of BCMA CAR-T in the treatment of elderly MM patients
In the KarMMa trial, PFS was comparable in older patients to younger patients. However, the efficacy and safety of elderly patients after receiving BCMA CAR-T have not been analyzed, and researchers from the United States have explored this. A total of 69 patients (33-77 years) were included in the study, and 15 patients (22%) were ≥70 years old at the time of CAR-T cell infusion. The demographic characteristics, physical status, and disease-related features of older patients are similar to those of younger patients (Table 4).
Table 4
Despite similar body weights, older patients had lower creatinine clearance (median creatinine clearance: 74.5 vs 108.7 mL/min, P<0.01) and preferred low-dose fludarabine for lymphocytic clearance (53% vs 17%, P<0.01). The incidence of any level of CRS, any level of ICANS, and persistent neutropenia was similar between the two groups (Table 5).
Table 5
Hypogammaglobulinemia developed in 93% of elderly patients and 73% of young patients ,p=0.16), respectively. A total of 5 infections occurred, all occurring in young patients. Median PFS (95% CI: 10.6-NR) and median OS (95% CI: NR-NR) were not achieved in older patients, and median PFS and median OS were 13.9 months (95% CI: 11.3-NR) and 30.3 months (95% CI: 24.8-NR) in younger patients (Figure 4). +100 days, 2 patients died, both of whom were progressive MM, and both occurred in young patients.
Figure 4
These results suggest that bcma CAR-T cell therapy toxicity does not increase in patients aged ≥70 years, although limited by small sample size and selection bias (more preference is given to older patients with better physical fitness for study). Hypogamma globulinemia is more common in older patients but does not correspond to a higher risk of infection. Low-dose fludarabine lymphocyte clearance did not reduce the efficacy of BCMA CAR-T cell therapy in elderly patients. The results suggest that BCMA CAR-T cell therapy can be used as an effective treatment regimen for elderly patients with RRMM.
References:
1. Doris Hansen, et al. 2022 IMS. Abstract#OAB-004.
2. Kevin Reyes, et al. 2022 IMS. Abstract#OAB-008.
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