Chinese Medical Team: Long Survival and Significant Benefits with BCMA CAR-T Treatment for RRMM: A 5-Year Outlook

**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.

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.

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.

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.

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!

WhatsApp: +86137 1795 9070

Email: doctor.huang@globecancer.com

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4 months ago Myeloma , CAR-T

2024 EBMT : China’s First RRMM CAR-T Therapy Equecabtagene Autoleucel: Efficacy Unaffected by Patients’ Baseline sBCMA Plasma Levels

2024 EBMT : China’s First RRMM CAR-T Therapy Equecabtagene Autoleucel: Efficacy Unaffected by Patients’ Baseline sBCMA Plasma Levels

RRMM

In recent years, CAR-T cell therapy targeting BCMA has emerged as a groundbreaking treatment for multiple myeloma, offering new hope to patients. At the 50th European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting, held from April 14-17, 2024, in Glasgow, the team led by Professor Qiu Lugui presented the latest subgroup analysis results from the FUMANBA-1 study (Abstract OS10-04) on China’s first BCMA-targeted CAR-T therapy, Iquilencel (CT103A).

BCMA (B-cell maturation antigen) is a promising therapeutic target for multiple myeloma (MM), with soluble BCMA (sBCMA) levels in the blood reflecting tumor burden. High sBCMA levels can interfere with the effectiveness of BCMA-targeted therapies, including CAR-T, by competing with cell-surface BCMA for binding, which can lead to reduced efficacy. In contrast, Iquilencel has been designed to minimize the impact of sBCMA on treatment outcomes through careful selection of its single-chain variable fragment (scFv).

The FUMANBA-1 phase II study (NCT05066646) in Chinese patients with relapsed/refractory multiple myeloma (RRMM) has demonstrated that Iquilencel can induce deep and durable responses, with a complete response (CR) rate of 82.4% and a 12-month progression-free survival (PFS) rate of 85.5%. This study aimed to explore whether baseline serum sBCMA levels affect clinical outcomes following Iquilencel infusion.

### Study Methods and Results

The study used enzyme-linked immunosorbent assay (ELISA) to measure serum sBCMA levels and digital droplet PCR (ddPCR) to monitor CAR transgene copy numbers in patients’ peripheral blood. Baseline serum sBCMA levels were classified into high (≥225.1 ng/mL) and low (<225.1 ng/mL) groups. Results showed that high sBCMA levels were significantly associated with high tumor burden, advanced R-ISS and DS stages, and high BCMA expression. However, there were no significant differences in CAR-T cell expansion, AUC (Area Under the Curve) during the first 28 days, or cell persistence between the high and low sBCMA groups.

Patients with high baseline sBCMA levels had overall response rates (ORR) and ≥CR rates of 100% and 80%, respectively, compared to 97.8% and 84% in the low sBCMA group. Analysis showed no significant correlation between baseline characteristics (including sBCMA levels) and CR/sCR achievement. Additionally, there were no significant differences in minimal residual disease (MRD) negativity rates, 18-month sustained MRD negativity rates, PFS, and overall survival (OS) between the two groups.

### Conclusion

The findings from the FUMANBA-1 study indicate that Iquilencel’s efficacy is not influenced by baseline sBCMA levels, making it a universally applicable and promising treatment option for RRMM patients. Its unique fast-dissociation and low-exhaustion properties, similar to those of healthy T-cell receptors, enable Iquilencel to remain effective and persistent in patients’ bodies regardless of sBCMA levels.

Professor Qiu Lugui from the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Professor Li Chunrui from Tongji Hospital, Huazhong University of Science and Technology, noted, “sBCMA is an important biomarker of tumor burden in multiple myeloma and a key factor influencing prognosis. Accumulation of sBCMA can inhibit the function of BCMA CAR-T cells. However, our study shows that Iquilencel can overcome the challenges posed by high baseline sBCMA levels, providing significant and lasting responses for RRMM patients.”

These results underscore Iquilencel as an ideal treatment choice for RRMM, offering hope for more effective and long-lasting therapeutic outcomes.

 

🎉🎉To assess whether the condition is suitable for CAR-T or clinic therapy, you can submit Advanced Medicine in China  for preliminary evaluation!

WhatsApp: +8613717959070

Email: doctor.huang@globecancer.com

#EBMT2024 #CAR_T #MultipleMyeloma #Iquilencel #EquecabtageneAutoleucel #sBCMA #CancerResearch #Immunotherapy #MedicalBreakthrough #Biopharmaceuticals

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5 months ago patient story , Myeloma

22 Days from Desperation to Rebirth! Chinese CAR-T Therapy Creates Survival Miracle for Thai Multiple Myeloma Patient

22 Days from Desperation to Rebirth! Chinese CAR-T Therapy Creates Survival Miracle for Thai Multiple Myeloma Patient

Patient story

Subtitle: Fighting for Love! A story of miraculous rebirth after all treatment options failed for a late-stage multiple myeloma patient in Thailand, who underwent CAR-T therapy in China.

Preface: When all treatment options had been exhausted, cancer progressed rapidly, and doctors regretfully said that Ms. M had no response to any medication. This situation could only lead to palliative care, meaning Ms. M had no chance to fight this disease anymore; her life was now on borrowed time. Fortunately, Ms. M’s family found new hope in China – CAR-T therapy. With the companionship of her family, Ms. M came to China and underwent the world’s first fully human BCMA CAR-T therapy. In just 22 days after treatment, all tumors miraculously disappeared, achieving complete remission (CR), and Ms. M was given a new lease on life!

In June 2021, the life of 58-year-old Ms. M experienced persistent back pain for over months. After detailed examinations at the hospital,resulting in a diagnosis of multiple myeloma. To quickly control the condition, Ms. M received treatments including PCD, DVD, bortezomib and lenalidomide, autologous hematopoietic stem cell transplantation.

In June 2023, the disease relapsed and Ms. M did not respond to any of these treatments. Local doctors informed Ms. M’s family that apart from palliative care, they were powerless, indicating that Ms. M’s life was now on borrowed time! Just as Ms. M was in dire straits, on June 30, 2023, the world’s first fully human BCMA CAR-T therapy – Equecabtagene Autoleucel, was shockingly launched in China, becoming a lifesaving straw for her. Ms. M and her family decided to seek treatment in China.

In September 2023, Professor Li Ping’s team at Shanghai Tongji Hospital developed a personalized Equecabtagene Autoleucel(BCMA CAR-T) therapy plan for Ms. M.

On September 8, 2023, Ms. M finally officially entered the CAR-T treatment process. After all examination items met the requirements, single-cell collection was performed first.

Bridge therapy began on September 11, 2023;

Local radiotherapy to relieve bone pain started on September 24, 2023;

Fludarabine plus cyclophosphamide chemotherapy was administered from October 9-12, 2023;

Finally, on October 14, a small bag of milky-white liquid was infused into Ms. M’s body. The doctor said that inside were billions of “special” T cells that could precisely kill multiple myeloma cells. Once inside the body, they would initiate a mode of frenzied sweeping, wiping out cancer cells completely.

What shocked everyone was that the examination results 22 days after CAR-T treatment showed that Ms. M had achieved hematologic CR, meaning that no cancer cells were detected in her blood. Her pain and anemia were also reversed. It was simply a miracle!

Every day now is precious to Ms. M. She can go shopping, chat with her family, enjoy delicious food with her family, and travel around the world with them, returning to the happy times before she fell ill. The only difference is that Ms. M and her family visit a fixed destination every month now – Shanghai, China. They have become accustomed to hearing the sacred announcement from the doctors here: no cancer in her body, continuing remission.

This is a microcosm of countless cancer patients overcoming the disease. The emergence of CAR-T cell therapy has brought new hope to cancer patients. I believe that in the future, more patients will be able to regain a new life like Ms. M.

Reference：

[1]Yuting Yan, et al. Blood Adv. 2019 Oct 8;3(19)：2895-2904.

[2] 2023 IMS. P-290.

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5 months ago patient story

22 Days from Desperation to Rebirth! Chinese CAR-T Therapy Creates Survival Miracle for Thai Multiple Myeloma Patient

22 Days from Desperation to Rebirth! Chinese CAR-T Therapy Creates Survival Miracle for Thai Multiple Myeloma Patient

Patient story

In July 2017, 58-year-old Ms. M was diagnosed with multiple myeloma. After receiving treatments at the best hospital in Thailand, including PCD, DVD, bortezomib and lenalidomide, autologous hematopoietic stem cell transplantation. The disease rapidly relapsed. Local doctors informed Ms. M’s family that apart from palliative care, they were powerless.

Just as Ms. M was in dire straits, on June 30, 2023, the world’s first fully human BCMA CAR-T therapy – Equecabtagene Autoleucel, was shockingly launched in China, becoming a lifesaving straw for her. Ms. M and her family decided to seek treatment in China.

In September 2023, Professor Li Ping’s team at Shanghai Tongji Hospital developed a personalized Equecabtagene Autoleucel(BCMA CAR-T) therapy plan for Ms. M. What shocked everyone was that the examination results 22 days after CAR-T treatment showed that Ms. M had achieved hematologic CR, meaning that no cancer cells were detected in her blood. Her pain and anemia were also reversed. It was simply a miracle!

Reference：

[1]Yuting Yan, et al. Blood Adv. 2019 Oct 8;3(19)：2895-2904.

[2] 2023 IMS. P-290.

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8 months ago Myeloma

#EBMT Conference Reveals the Best CAR-T Therapy for Multiple Myeloma – Equecabtagene Autoleucel

#EBMT Conference Reveals the Best CAR-T Therapy for Multiple Myeloma – Equecabtagene Autoleucel

Multiple myeloma

Introduction:

In recent years, there has been a breakthrough in the research of #CART therapy for relapsed and refractory #multiplemyeloma (RRMM). This treatment method holds promise to address the challenges of inadequate response depth and short duration of response in #RRMM patients, offering hope for achieving minimal residual disease (#MRD) negativity and functional cure in this population.

Key Findings at EBMT:

The upcoming 50th European Society for Blood and Marrow Transplantation (EBMT) congress is set to unveil abstracts shedding light on the efficacy of targeted #BCMA CAR-T therapies. A recent abstract titled “Indirect Comparison of the Effectiveness of Targeted BCMA CAR-T Products in RRMM (#MAIC)” for the first time reveals efficacy comparisons among four BCMA CAR-T products. The study demonstrates that Equecabtagene Autoleucel outperforms other BCMA CAR-T therapies in terms of overall response rate (#ORR) and complete response (#CR) rate, offering significant hope for RRMM patients.

#Equecabtagene Autoleucel: Pioneering Fully-human BCMA #CARTTherapy:

#EquecabtageneAutoleucel, the world’s first approved Fully-human BCMA CAR-T therapy, received priority review and approval in China on June 30, 2023. The MAIC analysis underscores its favorable efficacy. This article provides a systematic analysis of the efficacy data of Equecabtagene Autoleucel in the Chinese population over the past two years, as revealed in the dynamic disclosures at various international academic conferences post-approval.

Efficacy Data Highlights:

– In the #FUMANBA-1 Ib/II clinical study conducted in China, the sCR/CR rate reached an impressive 82.4% among RRMM patients.

– The latest data presented at the 2023 International Myeloma Society (#IMS) conference demonstrated a MRD negativity rate of 97.8% among the enrolled patients, indicating substantial tumor burden reduction.

– With a median follow-up of 18.07 months, long-term efficacy data showcased remarkable outcomes, including a median PFS not yet reached, 12-month continuous MRD negativity rate of 81.7%, and 12-month PFS rate of 85.5%.

Differentiating Factors:

– Equecabtagene Autoleucel exhibited shorter median time to response (#TTR) compared to other CAR-T therapies, indicating faster onset of action.

– The dissociation kinetics of Equecabtagene Autoleucel closely resemble those of natural T cells, facilitating efficient activation, killing, and proliferation within the body.

– Its rapid dissociation pattern minimizes CAR-T cell exhaustion, ensuring sustained efficacy and long-term surveillance against tumor recurrence.

Conclusion:

The emergence of Equecabtagene Autoleucel heralds a new era in CAR-T therapy for RRMM, offering superior efficacy and durable responses. With its unique structural advantages and promising clinical data, Equecabtagene Autoleucel stands as a beacon of hope for RRMM patients worldwide, bringing them closer to achieving disease control and improved quality of life.

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

WhatsApp: +8613717959070

#chineseMedicine #chineseresearch #cancerresearch #cancertreatment #myeloma #bloodtumor #cancer #cancerreseach

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