**Chinese Medical Team: Long Survival and Significant Benefits with BCMA CAR-T Treatment for RRMM: A 5-Year Outlook**
RRMM
Chimeric antigen receptor (CAR) T-cell therapy is one of the most promising new treatments for relapsed/refractory multiple myeloma (RRMM), but reports on its long-term efficacy and safety are limited. As early as 2022, Professor Du Juan’s team from the Department of Hematology at Shanghai Changzheng Hospital published a Phase I/II study demonstrating that patients with poor physical status could also benefit from CAR-T therapy. Recently, the team updated their findings with a five-year long-term follow-up, focusing on factors affecting long-term clinical benefits. The results were published in *Clinical Cancer Research*. The following summary of the study’s content is provided by *Cancer Information* for readers’ benefit.
### Evidence for Long-Term Efficacy and Safety of BCMA CAR-T Cell Therapy
#### Patient Characteristics
The study included 49 RRMM patients who had all received at least three prior lines of therapy before undergoing BCMA CAR-T cell treatment. At enrollment, 20 patients (40.82%) had poor physical status (ECOG performance status of 3-4), 42.86% had high-risk cytogenetic features, and 63.27% had received four or more lines of treatment. At the time of infusion, 79.59% had progressive disease. Among the patients with poor physical status, 30% had extramedullary disease (EMD), 45% had high-risk cytogenetic features, 70% had received four or more lines of treatment, and 80% had progressive disease after their last line of treatment.
#### Efficacy Evaluation of BCMA CAR-T Cell Therapy HDS269B
After a median follow-up of 59.0 months, the study showed an overall response rate (ORR) of 77.55%. The ORR was similar across patients with different ECOG scores. The median progression-free survival (PFS) was 9.5 months, and the median overall survival (OS) was 20.0 months. The five-year PFS and OS rates were 21.3% and 31.4%, respectively. For patients with ECOG scores of 0-2, the median PFS was 11.0 months, compared to 4.0 months for those with scores of 3-4 (P=0.18). The median OS was 41.8 months for ECOG 0-2 patients and 10.5 months for ECOG 3-4 patients (P=0.015).
Patients who had previously undergone four or more lines of therapy had significantly shorter PFS and OS compared to those who had received fewer than four lines (PFS: P=0.012; OS: P=0.0049). Among the 11 patients with EMD at enrollment, the ORR was 64% for those with EMD and 82% for those without EMD. However, median PFS and OS were notably shorter in patients with EMD (PFS: 3.0 months vs. 10.5 months, P=0.06; OS: 5.0 months vs. 24.0 months, P=0.03).
#### MRD-Negative Status and CAR-T Cell Persistence Indicate Better Long-Term Survival
Minimal residual disease (MRD) negativity was significantly associated with longer PFS and OS. In this study, MRD data were available for 22 patients on day 28 post-infusion, with 14 patients (63.64%) achieving MRD negativity (10^-4). These patients experienced significantly longer PFS and OS compared to MRD-positive patients. Similar associations were observed with MRD status at 3 and 6 months post-infusion.
The expansion of CAR-T cells was also closely related to clinical outcomes. Patients who achieved partial response (PR) or better had higher CAR-T cell peak levels. Patients without disease progression five years post-infusion had significantly higher CAR-T cell expansion peaks than those with progression. Additionally, the duration of CAR-T cell persistence correlated with longer PFS and OS, with patients having CAR-T cells persisting for ≥6 months, ≥12 months, ≥24 months, and ≥36 months showing significantly better PFS and OS than those without detectable CAR-T cells.
#### Controlled Safety Profile of BCMA CAR-T Cell Therapy HDS269B
No new CAR-T cell-related toxicities were observed during long-term follow-up. All patients experienced at least one adverse event (AE), with the most common long-term (≥28 days post-infusion) grade ≥3 AEs being hematologic in nature. No second primary malignancies or delayed immune effector cell-associated neurotoxicity syndrome (ICANS) were observed.
This study also included survival analysis, classifying patients by PFS and OS. The results indicated that ECOG 0-2 status, fewer than four prior therapies, and CAR-T cell persistence for ≥6 months were independently associated with longer survival.
### The Potential of BCMA CAR-T Therapy and the Need for Future Optimization
Through a five-year long-term follow-up of 49 RRMM patients, this study systematically evaluated the efficacy and safety of BCMA CAR-T cell therapy HDS269B. The findings suggest that poor physical status is not a contraindication for CAR-T therapy, thus broadening the indications for this treatment. While the results are encouraging, the study has some limitations, including its open-label, single-arm design and small sample size, which, combined with the long follow-up period, could lead to some patient attrition. Furthermore, despite the lack of new severe toxicities, long-term safety requires continued observation.
Overall, this study underscores the importance of BCMA CAR-T cell therapy in the treatment of RRMM and provides a crucial basis for exploring and applying CAR-T immunotherapy in the frontline treatment of multiple myeloma.
To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China for preliminary evaluation!
Email: doctor.huang@globecancer.com
