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4 months ago CAR-T

2024 EHA | New Generation BCL-2 Inhibitor Sonrotoclax Expected to Be a New Treatment Option for RRMM

RRMM

The 29th Annual Meeting of the European Hematology Association (EHA) was held from June 13-16, 2024, in Madrid, Spain. During this event, the results of the study on the new-generation BCL-2 inhibitor Sonrotoclax (BGB-11417) combined with dexamethasone for the treatment of relapsed/refractory multiple myeloma (RRMM) patients with t(11;14) were presented.

Ib/II Phase Study of Sonrotoclax (BGB-11417) Combined with Dexamethasone for the Treatment of RRMM with t(11;14)

Study Background

The B-cell lymphoma-2 (BCL-2) protein helps multiple myeloma (MM) tumor cells evade apoptosis and promote cell survival. Studies have found that MM cells with t(11;14) have significantly higher BCL-2 protein expression compared to other cells. BCL-2 inhibitors can block anti-apoptotic mechanisms and induce cell apoptosis. Currently, data have shown that BCL-2 inhibitors have significant anti-MM potential in RRMM patients with t(11;14) who have failed multiple lines of treatment. However, to date, no BCL-2 targeted therapy has been approved for MM treatment.

Sonrotoclax (BGB-11417) is a new-generation BCL-2 inhibitor. Preclinical studies have found that it has over ten times the BCL-2 inhibitory ability of the first-generation BCL-2 inhibitors, a shorter half-life, and no dose accumulation. BGB-11417-105 (NCT04973605) is an ongoing Ib/II phase trial aimed at evaluating the efficacy and safety of Sonrotoclax combined with dexamethasone ± carfilzomib/daratumumab/pomalidomide in treating RRMM patients with t(11;14). The latest data from this study were reported at this EHA meeting.

Study Design

The enrolled patients were all RRMM with t(11;14), who had failed at least three treatments, including proteasome inhibitors (PI), immunomodulatory drugs (IMIDs), and anti-CD38 monoclonal antibodies, and were refractory/relapsed to the most recent treatment. In the first part, dose escalation cohorts, patients took 80, 160, 320, or 640 mg of Sonrotoclax daily, combined with 40 mg of dexamethasone weekly until intolerance, disease progression, or death. The primary endpoints were safety/tolerability, determining the maximum tolerated dose (MTD)/maximum assessed dose (MAD), and recommending the dose for the expansion phase (RDFE). The second part, dose expansion, primarily evaluated the tolerability and antitumor activity of Sonrotoclax combined with dexamethasone ± carfilzomib/daratumumab/pomalidomide.

Study Results

The initial report at 2023 ASH showed that Sonrotoclax (640 mg) was well tolerated, with no dose-limiting toxicities (DLTs) observed in any patients, establishing 640 mg as the RDFE. The overall response rate (ORR) for this cohort was 70%, and the rate of very good partial response (≥VGPR) was 40%.

Updated in this report: as of March 25, 2024, 32 patients received the RDFE dose of 640 mg Sonrotoclax combined with dexamethasone (10 in the first part and 22 in the second part). The median follow-up time was 4.6 months (0.1-19 months).

The median age of patients was 69 years (48-80 years), with a median of 3 prior lines of treatment (1-12 lines), and 28.1% had high-risk cytogenetic abnormalities. All patients had been exposed to PI and IMiD treatments, and 72% had been exposed to anti-CD38 monoclonal antibody treatments. 56% were PI-refractory, 72% were IMiD-refractory, 56% were anti-CD38 monoclonal antibody-refractory, and 47% were triple-refractory.

Safety

No patients experienced DLTs. The most common treatment-emergent adverse events (TEAEs) were fatigue and insomnia (28% each), diarrhea (22%), constipation, and nausea (16% each). Only 4 patients (13%) experienced hematologic TEAEs (grade 3 thrombocytopenia, grade 1 and 3 platelet count decrease, and grade 3 neutropenia). Two patients died, both unrelated to treatment (one due to pancreatic cancer complications and one due to liver cancer and liver failure).

Efficacy

Among the 24 evaluable patients, the ORR was 75%, with a ≥VGPR rate of 50%. The complete response (≥CR) rate was 21% (CR, n=4; sCR, n=1), with two patients achieving minimal residual disease (MRD) negativity (10^-5). The median time to response was 0.7 months, and the median duration of response (DOR) was 8 months. As of the follow-up, the longest DOR was 18 months.

Conclusion

Sonrotoclax (640 mg) combined with dexamethasone was well tolerated in heavily pretreated RRMM patients with t(11;14), with low rates of hematologic toxicity and infection. It provided deep and durable responses: ORR was 75%, ≥VGPR rate was 50%, and ≥CR rate was 21%. This study will continue to explore Sonrotoclax in combination with other novel agents.

Interpretation by Professor Lu Jin

The t(11;14) translocation is a common genetic abnormality in MM patients, present in approximately 15%-20% of newly diagnosed MM cases. Before the era of novel drugs, many researchers believed that patients with t(11;14) had favorable treatment outcomes and were classified as a standard-risk group. However, recent studies have found that patients with t(11;14) are less sensitive to bortezomib regimens, and even with the VRd regimen, patients with t(11;14) have significantly lower deep response rates (≥VGPR) and PFS benefits compared to other standard-risk patients. This suggests that t(11;14) may be an influencing factor for poor efficacy of novel drugs, necessitating other therapies to improve prognosis.

Studies have found that tumor cells with t(11;14) often have high BCL-2 expression and high sensitivity to BCL-2 inhibitors. The phase III CANOVA study demonstrated that venetoclax combined with dexamethasone resulted in deeper response rates (ORR 62% vs. 35%, p<0.001; ≥VGPR rate 39% vs. 14%, p<0.001) and longer median PFS (9.1 months vs. 4.9 months, p=0.237) compared to pomalidomide combined with dexamethasone in treating RRMM patients with t(11;14), though without significant statistical difference. The failure to meet the primary endpoint might be due to more patients in the control group not reaching IMWG-defined disease progression and thus being treated with new regimens, resulting in censored data in the initial PFS analysis. In the latest post-hoc analysis, including new treatment as an event in PFS, the analysis showed a significant statistical difference in median PFS (9.4 months vs. 4.0 months, p=0.003).

Therefore, the benefits of BCL-2 inhibitors still warrant further exploration. Sonrotoclax is a second-generation highly selective and potent BCL-2 inhibitor. In preclinical trials, Sonrotoclax had an IC50 for BCL-2 protein over ten times lower than that of the first-generation BCL-2 inhibitors (0.014 nM vs. 0.2 nM). It also showed ≥2000 times selectivity over BCL-XL, BCL-W, MCL-1, and BCL2A1 and stronger cytotoxicity against MM cell lines. Additionally, Sonrotoclax has a shorter half-life (approximately 4.5 hours), allowing more flexible exploration of rapid dose escalation plans without the risk of off-target toxicity due to drug accumulation.

The Ib/II phase study reported at this EHA meeting demonstrated that Sonrotoclax combined with dexamethasone was well tolerated in RRMM patients previously treated with multiple lines of therapy. The 640 mg RDFE dose achieved a 75% ORR, ≥VGPR rate of 50%, and ≥CR rate of 21%. We look forward to the release of more results from Sonrotoclax combination therapies. Additionally, as the proportion of t(11;14) in systemic light chain amyloidosis and plasma cell leukemia is higher than in MM, the exploration of BCL-2 inhibitors in these plasma cell diseases is also ongoing.

Professor Lu Jin

Chief Physician, Professor, Ph.D. Supervisor

Peking University People’s Hospital, Peking University Institute of Hematology

Specializes in clinical and laboratory research on multiple myeloma, primary systemic amyloidosis, lymphoma, and cellular immunotherapy.

General Secretary and Standing Committee Member of the Hematology Physician Branch of the Chinese Medical Doctor Association

President of the Hematology Physician Branch of the Beijing Medical Doctor Association

Vice Chairman of the Multiple Myeloma Professional Committee and the Histiocyte Disease Professional Committee of the Chinese Medical Doctor Association

Vice President of the Hematology Branch of the Chinese Society of Geriatrics and Chairman of the Multiple Myeloma Academic Committee

Deputy Leader of the Plasma Cell Group of the Hematology Branch of the Chinese Medical Association

Deputy Leader of the Multiple Myeloma and Related Diseases Professional Group of the Hematology Professional Committee of the Chinese Women Physicians Association

Member of the Chinese and International Primary Systemic Amyloidosis Collaboration Group

Member of the International Myeloma Working Group and the Asia-Pacific Myeloma Working Group

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

#Sonrotoclax #RRMM #BCL2Inhibitor #MultipleMyeloma #EHA29 #Hematology #NewTreatment #CancerResearch #2024EHA

4 months ago CAR-T

Sustained 7-Month CR, Liver Extramedullary Disease Disappearance: Equecabtagene Autoleucel Brings High-Quality Survival Hope to Ultra-High-Risk RRMM Patients with Extramedullary Disease

### Sustained 7-Month CR, Liver Extramedullary Disease Disappearance: Equecabtagene Autoleucel Brings High-Quality Survival Hope to Ultra-High-Risk RRMM Patients with Extramedullary Disease

RRMM Patients

In December 2019, a man in his 50s was diagnosed with multiple myeloma (MM) at a hospital in Shenzhen, China. The patient had high-risk cytogenetic abnormalities (17p deletion) and underwent various treatments over more than three years, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and CD38 monoclonal antibodies. Despite these treatments, the patient experienced a second relapse. This relapse was characterized by a P53 gene mutation and liver extramedullary invasion, classifying it as an ultra-high-risk situation. Although the patient initially refused an autologous stem cell transplant (ASCT), he was eventually persuaded to collect sufficient stem cells. However, due to concerns about the side effects of high-dose chemotherapy, he opted for CAR-T therapy.

### Personalized Treatment: From ASCT to CAR-T Therapy

Under the care of Professor Chen’s team at the hospital, the patient was evaluated for CAR-T therapy. Despite the risks, he underwent the treatment and showed significant improvement. As of March 2024, he has maintained a complete response (CR) for seven months, with PET/CT scans indicating the disappearance of liver extramedullary disease.

#### Patient Background

– Age: 54

– Initial Symptoms: Back pain after exercise

– Diagnosis: Multiple Myeloma (IgA κ type, DS I A stage, ISS I stage, R-ISS II stage, mSMART high-risk)

### Treatment Journey

– 2019: Diagnosed with MM; high-risk cytogenetic abnormality (17p deletion)

– 2020-2022: Treated with PIs, IMiDs, and CD38 monoclonal antibodies

– Early 2023: Second relapse with P53 mutation and liver extramedullary disease

– July 2023: Stem cell collection for ASCT

– August 2023: Initiated CAR-T cell (Equecabtagene Autoleucel) therapy

– September 2023: Discharged with strict complete response (sCR)

– March 2024: PET/CT scan confirms sustained complete response (CR) with no liver lesions

### Breakthrough Results and Future Prospects

CAR-T therapy has emerged as a promising treatment for relapsed and refractory multiple myeloma (RRMM), especially for patients resistant to conventional therapies. This case highlights the importance of personalized treatment plans, considering disease factors, previous treatment outcomes, and patient preferences. Equecabtagene Autoleucel (IKEA-Lunsay) CAR-T therapy has given this high-risk patient a new lease on life and holds the potential to offer hope to many more MM patients in China.

By showcasing such success stories, we aim to raise awareness about the advancements in CAR-T therapy and its significant impact on improving the quality of life for MM patients. This breakthrough not only marks a significant achievement for the hospital but also signals a new era of hope for countless MM patients.

🎉🎉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

#MedicalBreakthrough #CARTTherapy #MultipleMyeloma #CancerTreatment #PatientSuccess #HealthcareInnovation #CancerResearch #MMTreatment #LifeSavingTherapies #MedicalAdvancements #HealthcareHeroes #InnovativeMedicine #CancerCare #HopeForMM #CancerAwareness

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

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

4 months ago Myeloma

2024 EHA | Breaking Through Multiple Myeloma Treatment Bottlenecks: Significant Advances of Equecabtagene Autoleucel in High-Risk NDMM Patients

Multiple Myeloma

Multiple Myeloma (MM) is a malignant plasma cell disorder and one of the most common hematologic malignancies. In China, approximately 20,000 new cases of newly diagnosed multiple myeloma (NDMM) are reported annually, with a median age at diagnosis over 60 years. It is reported that Chinese MM patients generally exhibit higher rates of cytogenetic abnormalities, with an incidence rate exceeding 40%, which is significantly higher than in Western countries.

High-risk MM patients often respond poorly to existing treatment regimens and face limited treatment options. Many elderly patients are frail and have multiple comorbidities, making them less tolerant of the adverse reactions associated with current therapies, particularly autologous stem cell transplantation (ASCT). Once the disease progresses to a refractory/relapsed state, the combination of advanced age, frailty, and high-risk cytogenetic abnormalities leads to limited salvage treatment options, worsening efficacy, and poor prognosis. Thus, selecting effective frontline therapy for NDMM patients, especially high-risk elderly patients unsuitable for transplantation, is a pressing clinical need, requiring innovative therapies to supplement existing treatments. The new generation of cell immunotherapies, exemplified by Equecabtagene Autoleucel, holds promise to fill this gap and potentially become a breakthrough for high-risk NDMM.

In the FUMANBA-1 study, which included 69.5% high-risk patients, Equecabtagene Autoleucel achieved an ORR of 96.1% and has been approved in China for treating third-line or later relapsed/refractory multiple myeloma (R/R MM) patients. This EHA meeting is the first to present oral data on the efficacy and safety of Equecabtagene Autoleucel in the FUMANBA-2 study for high-risk, newly diagnosed, transplant-ineligible MM patients.

### Study Introduction

FUMANBA-2 is a multicenter, open-label, single-arm Phase I study designed to evaluate the efficacy and safety of Equecabtagene Autoleucel in transplant-ineligible NDMM patients with 100% high-risk features (defined by mSMART 3.0: RISS Stage III, double-hit, or triple-hit). Patients received four cycles of induction therapy, including the VRd regimen (Bortezomib, Lenalidomide, Dexamethasone), the VCD regimen (Bortezomib, Cyclophosphamide, Dexamethasone), or the PAD regimen (Bortezomib, Doxorubicin, Dexamethasone). After the third cycle of induction therapy, T cells were collected from patients unsuitable for ASCT and Equecabtagene Autoleucel was prepared. After lymphodepletion, patients received a single infusion of Equecabtagene Autoleucel at a dose of 1.0 x 10^6 CAR-T cells/kg. The primary efficacy endpoints were the proportion of MRD-negative patients and progression-free survival (PFS). Secondary endpoints included objective response rate, duration of response, safety, pharmacokinetics, and pharmacodynamics.

### Study Results

As of January 25, 2024, 16 patients received Equecabtagene Autoleucel, with a median age of 58.5 years (51-69) and a median follow-up time of 13.1 months (7.9-24.3). All patients had high-risk cytogenetics, with 62.5% (10/16) being double-hit, 12.5% (2/16) being triple-hit, and 25% (4/16) having extramedullary disease. 37.5% (6/16) were R-ISS Stage III, with one patient each combining R-ISS Stage III with double-hit and triple-hit characteristics.

The median follow-up time after Equecabtagene Autoleucel infusion was 7.46 months (2.8-18.1). The median PFS was not reached, with a 12-month PFS rate of 84.4% (95% CI: 49.31-96.00). All subjects achieved MRD negativity, with 71.4% (95% CI: 25.8-92.0) maintaining MRD negativity for over 12 months. The objective response rate (ORR) was 100%, with 93.8% (15/16) achieving stringent complete response (sCR).

Grade 1-2 cytokine release syndrome (CRS) occurred in 68.8% (11/16) of patients, with no grade 3 or higher CRS, immune effector cell-associated neurotoxicity syndrome (ICANS), or neurotoxicity. The most common grade 3 or higher drug-related adverse events were hematologic, with a 25.0% (4/16) incidence of grade 3 or higher infectious disease adverse events.

The median peak CAR copy number in peripheral blood was reached on day 10 (7-21) post-infusion, with a median peak level of 79,681.299 copies/μg gDNA. 81.25% (13/16) of patients achieved free B cell maturation antigen (sBCMA) clearance within one month post-infusion. Median peak levels of inflammatory cytokines IL-6, CRP, and ferritin were 64.28 pg/mL (9.12-3017.83), 49.30 mg/L (3.66-117.30), and 553.35 ng/mL (68.10-2349.00), respectively. The median peak times for IL-6 and CRP were day 7 and day 10, respectively, with no significant change in serum ferritin levels compared to pre-infusion.

### Study Outlook

The FUMANBA-2 study of Equecabtagene Autoleucel demonstrates the efficacy and safety of a novel fully human BCMA CAR-T therapy in high-risk, transplant-ineligible, newly diagnosed multiple myeloma patients. This is the first international report of CAR-T therapy as frontline treatment in this specific population. The study highlights the potential application of cell immunotherapy in the MM field. Compared to traditional chemotherapy and new drug treatments, frontline CAR-T therapy for NDMM has the potential to further improve response rates, extend survival, and improve prognosis, particularly for high-risk cytogenetic abnormalities and high tumor burden. For elderly and frail patients who are unsuitable for hematopoietic stem cell transplantation, CAR-T therapy may fill the treatment gap to some extent. The one-time treatment approach, as opposed to continuous chemotherapy or multiple transplants, offers patients better quality of life and treatment convenience. Although CAR-T therapy carries risks such as CRS and neurotoxicity, these side effects are manageable in many studies, and safety improves with treatment experience and management strategies. Bringing CAR-T therapy to the frontline provides patients with more diverse and promising treatment options. However, large-scale, long-term follow-up studies are needed to validate its long-term efficacy and survival benefits, and further exploration and optimization are required for the best administration timing, regimen, and duration.

In summary, the FUMANBA-2 study of Equecabtagene Autoleucel shows significant treatment potential in newly diagnosed, transplant-ineligible multiple myeloma patients. With accumulating research evidence and advances in CAR-T technology, we anticipate CAR-T therapy will benefit more patients in the future.

🎉🎉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

#EquecabtageneAutoleucel #MultipleMyeloma #MMTreatment #HighRiskMM #NDMM #CAR_Therapy #Immunotherapy #BloodCancer #OncologyResearch #EHA2024 #CancerBreakthrough #CellTherapy #MyelomaTreatment #ClinicalTrials #InnovativeMedicine #HealthcareAdvancements

5 months ago CAR-T , Myeloma

#EBMT / The Success Story of Equecabtagene Autoleucel: The World’s First Fully Human CAR-T for Multiple Myeloma

Multiple Myeloma

In recent years, CAR-T cell therapy has made groundbreaking progress in the field of relapsed/refractory multiple myeloma (RRMM), offering hope to patients struggling with limited treatment options. Recent data shows that Equecabtagene Autoleucel achieved an impressive complete response (CR) rate of 82.4% in Chinese clinical trials, garnering widespread attention for its outstanding efficacy.

### Breakthrough Research Findings

At the upcoming 50th Annual Meeting of the European Group for Blood and Marrow Transplantation (EBMT) in the UK, a study titled “Matching-Adjusted Indirect Comparison of Effective Characteristics Among Different BCMA Targeting CAR-T in Treatment of Relapsed or Refractory Multiple Myeloma (MAIC)” will be presented. This study compares the efficacy of four BCMA-targeted CAR-T products, revealing that Equecabtagene Autoleucel’s overall response rate (ORR) and CR rate are significantly superior to those of other comparators, especially in terms of CR rate.

### Clinical Performance of Equecabtagene Autoleucel

Equecabtagene Autoleucel is the world’s first fully human CAR-T product approved for marketing, having received priority review approval in China on June 30, 2023. The approval is based on results from the FUMANBA-1 Ib/II clinical study conducted across 14 centers in China. The study demonstrated that among 91 RRMM patients who had not previously received CAR-T therapy and had relapsed after multiple lines of treatment, Equecabtagene Autoleucel achieved a sCR/CR rate of 82.4%, with 97.8% of patients reaching minimal residual disease (MRD)-negative status.

### Pharmacodynamics and Pharmacokinetics Advantages

Compared to other BCMA-targeted CAR-T products, Equecabtagene Autoleucel shows significant advantages in pharmacodynamics and pharmacokinetics. Data indicates that Equecabtagene Autoleucel has a median time to response (TTR) of 15 days, and 62.3% of patients maintained CAR-T cell persistence for over 6 months. These findings suggest that Equecabtagene Autoleucel not only acts quickly but also remains effective in the body for an extended period, providing long-lasting therapeutic benefits.

### Structural Advantages Unveiled

Equecabtagene Autoleucel’s design includes unique structural advantages that minimize CAR-T cell exhaustion within the patient’s body. Research shows that Equecabtagene Autoleucel’s dissociation constant (Kd) is close to the natural dissociation kinetics of human T cells, with a dissociation time of about 6 minutes. This allows CAR-T cells to efficiently activate, kill, and proliferate within the body. In contrast, other BCMA-targeted CAR-T products have lower dissociation constants and longer dissociation times, which can lead to CAR-T cell exhaustion and reduced longevity.

### Long-Term Efficacy Outlook

Equecabtagene Autoleucel’s excellent performance in clinical trials brings new hope to RRMM patients. The long-term efficacy data in Chinese patients are particularly noteworthy. As time progresses, further clinical data will continue to validate Equecabtagene Autoleucel’s efficacy and safety, offering more effective treatment options for RRMM patients worldwide.

The success of Equecabtagene Autoleucel is not only due to its remarkable clinical efficacy but also the extensive scientific research and innovative technology behind it. This groundbreaking therapy sheds new light on the treatment of multiple myeloma and paves the way for future advancements in CAR-T cell therapy.

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

#CART #MultipleMyeloma #EquecabtageneAutoleucel #CancerTreatment #Biopharmaceuticals #MedicalBreakthrough #Oncology #InnovativeTherapies #ClinicalResearch #HealthAdvancements

5 months ago CAR-T

One Year After Approval: How Effective is China’s First BCMA-Targeted CAR-T Therapy in Treating Multiple Myeloma?

### One Year After Approval: How Effective is China’s First BCMA-Targeted CAR-T Therapy in Treating Multiple Myeloma?

Multiple Myeloma

“In the past 20 years, the treatment of multiple myeloma has advanced rapidly, thanks in large part to the swift progress in drug development. Over the past year, China’s first independently developed and the world’s first fully human BCMA-targeted chimeric antigen receptor T-cell (CAR-T) therapy was approved. In our real-world clinical applications, we have treated over 20 patients with an overall effectiveness rate of nearly 100%.”

On June 30, 2024, exactly one year after the approval of China’s first BCMA-targeted CAR-T therapy (Iquilonsen Injection), and also the world’s first fully human BCMA-targeted CAR-T therapy, how effective has the treatment been for patients? Professor Qiu Lugui, Director of the Lymphoma Treatment Center at the Chinese Academy of Medical Sciences Hematology Hospital, was interviewed by the People’s Daily Health Client.

“Multiple myeloma has a slow onset and early stages often show no obvious symptoms, making it easy to misdiagnose. To date, once diagnosed, the vast majority of patients experience one or more relapses, entering a refractory state, which is an incurable disease,” Professor Qiu Lugui told the People’s Daily Health Client.

Professor Qiu explained that current drugs for treating multiple myeloma fall into three categories: immunomodulators, proteasome inhibitors, and CD38 monoclonal antibodies. The indications for these drugs have gradually moved from refractory cases to frontline treatments, transforming multiple myeloma from a deadly disease with a median survival of around three years to a relatively controllable malignant hematological tumor with a median survival of 10 years or more after systematic multi-drug therapy.

CAR-T cell therapy is a cutting-edge technology for treating malignant hematological tumors. China’s independently developed fully human BCMA-targeted CAR-T drug (Iquilonsen Injection) is designed for multiple myeloma patients who have relapsed or whose disease remains uncontrolled despite traditional treatments including proteasome inhibitors and immunomodulators.

One particularly memorable case for Professor Qiu was a 70-year-old patient. “At that time, the patient was extremely weak and had already undergone all available treatments, including two types of immunomodulators, two types of proteasome inhibitors, CD38 monoclonal antibodies, and intensive chemotherapy, with no other effective options left,” recalled Professor Qiu. “However, the patient had a strong desire to live. Seeing his eager eyes, we couldn’t remain indifferent.”

“After confirming with the patient, we decided to proceed with the fully human BCMA-targeted CAR-T Iquilonsen therapy. One month after the treatment, the first evaluation showed complete remission. To date, the patient remains in complete remission,” said Professor Qiu.

“In real-world applications, we have treated over 20 patients with an overall effectiveness rate approaching 100%. However, due to the high cost of the drug and the fact that it is not covered by medical insurance, making the drug accessible remains a challenge,” Professor Qiu told the People’s Daily Health Client. “Currently, there are two methods to address this issue: one is to meet the needs of economically disadvantaged patients through commercial insurance; the other is to meet the needs of patients who meet the criteria for inclusion in CAR-T clinical research.”

“Additionally, in the year since the approval of China’s first CAR-T therapy for treating multiple myeloma, not only domestic patients but also patients from Europe, Asia-Pacific, Africa, and other regions have come to China for CAR-T treatment. Overall treatment driven by dynamic prognostic stratification will be the future path to cure for multiple myeloma patients both in China and globally,” said Professor Qiu.

#MultipleMyeloma #CARTTherapy #CancerTreatment #MedicalBreakthrough #BCMATargeted #ChinaHealthcare #InnovativeMedicine #PatientSuccess #GlobalHealth #Hematology #Immunotherapy

5 months ago CAR-T

IASO Bio’s Equecabtagene Autoleucel Injection Wins “China First-in-Class” Award, Showcasing China’s Biopharmaceutical Innovation

Multiple myeloma

On June 28, 2024, at the “2024 First CBA-China Annual Conference” hosted by the Chinese Biopharmaceutical Association, USA, at the Suzhou International Expo Centre, IASO Bio’s Equecabtagene Autoleucel Injection was honored with the “China First-in-Class Targeted Drug” award. This award recognizes the drug’s outstanding innovation and therapeutic efficacy, making it the only brand in the cell therapy category to receive this prestigious honor. This accolade not only highlights IASO Bio’s innovative capabilities and research strength in the biopharmaceutical field but also represents the rise of China’s biopharmaceutical industry on a global scale.

In recent years, China’s innovation capabilities in the biopharmaceutical field have significantly improved. From 2015 to 2021, most “first-in-class” drugs on the market were dominated by foreign companies. However, from 2021 to 2023, data on approved new drugs in China showed that among 35 “first-in-class” products, nearly half were from domestic companies, with four being independently developed. This not only marks the rise of China’s innovative drugs but also demonstrates China’s increasing competitiveness in the global biopharmaceutical industry.

The success of IASO Bio’s Equecabtagene Autoleucel Injection is the best embodiment of the innovative power of China’s biopharmaceutical industry. In the future, IASO Bio aims to leverage more international platforms to advance biopharmaceutical technology in China and worldwide, contributing significantly to human health.

About IASO Bio

IASO Bio is a biopharmaceutical company focused on the research, development, production, and sale of innovative cell therapies. The company bases its innovation on the development of cell therapies for hematologic malignancies and antibody drugs, expanding into autoimmune diseases. IASO Bio possesses full capabilities from early discovery, clinical development, and regulatory submission to commercial production.

The company has more than ten innovative drug candidates in various stages of development, among which Equecabtagene Autoleucel Injection (a fully human BCMA CAR-T product) has been approved for marketing by the National Medical Products Administration (NMPA) and has received FDA approval for clinical trials in the United States for the treatment of relapsed/refractory multiple myeloma.

With a strong management team, an innovative product pipeline, in-house GMP production facilities, and outstanding clinical development capabilities, IASO Bio is dedicated to providing transformative, curative innovative therapies, bringing hope for a cure to patients in China and worldwide.

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

#IASOBio #InnovationInMedicine #ChinaFirstInClass #EquecabtageneAutoleucel #GlobalHealth #multiplemyeloma #RRMM

5 months ago CAR-T

Breakthrough Therapy Brings New Hope: Swiss Patient Thomas Begins CAR-T Treatment at Tongji Hospital, Wuhan

Professor Li Chunrui’s team at Tongji Hospital in Wuhan successfully conducted a case of chimeric antigen receptor T-cell (CAR-T) immunotherapy for a patient with relapsed and refractory multiple myeloma, offering new life to Swiss patient Thomas.

Thomas, a 54-year-old patient from Switzerland, has been battling multiple myeloma for nearly ten years. Initially diagnosed in 2016, he has endured severe bone pain and undergone multiple rounds of systemic chemotherapy and monoclonal antibody therapy. Although his condition was temporarily controlled, repeated relapses, with the most recent in 2022, made treatment increasingly challenging.

However, the global development of CAR-T therapy has reignited hope. The introduction of FUCASO (Eque-cel), the first fully human CAR-T product in mainland China, has brought new light to Thomas. This groundbreaking treatment not only boasts low immunogenicity but also offers prolonged efficacy, enabling patients to return to a high quality of life.

Thomas ultimately chose to receive the cutting-edge CAR-T therapy at Tongji Hospital, seeking a fundamental breakthrough in his treatment. The apheresis procedure was conducted by the hospital’s top hematology team, who possess international-level expertise and place special emphasis on patient-specific needs and treatment safety. The attending physician elaborated on the apheresis process in an interview, saying, “We precisely collected T-cells from Thomas’s body, then modified these cells in a controlled environment to specifically target multiple myeloma cancer cells. The use of FUCASO greatly enhanced the treatment’s specificity and success rate.”

Thomas expressed high recognition and appreciation for the hospital team’s professionalism and the transparency of the treatment process. Tongji Hospital leveraged its advanced technology and equipment to provide Thomas with a smooth and efficient apheresis experience, ensuring high-quality T-cell collection and paving the way for the subsequent treatment.

Thomas is now filled with confidence and anticipation, looking forward to the new life that CAR-T therapy promises. This new beginning marks a significant step in his treatment journey, injecting new hope into his path to recovery.

We will continue to follow up on the patient’s subsequent treatment and report on the progress.

CART MultipleMyeloma FUCASOJourney Equecel TongjiHospital CancerSurvivor BloodCancer Immunotherapy FullyHumanCART CancerTreatment

5 months ago Myeloma , patient story

The Journey of an Indian Cancer Patient Seeking Treatment in China: Gratitude to Be Brought Back to India

patient story

“Before coming to China for treatment, I was filled with worries. My condition was not optimistic, and I was afraid I might never see my family again… But after arriving here, everyone I met was so warm and welcoming. The doctors are not only professional but also incredibly patient. I am now truly, truly happy, and I will bring this gratitude back to India.” — Ms. Savita

This is the true story of Ms. Savita from India, a multiple myeloma patient. Her journey to seek medical treatment was long and arduous, and she was often moved to tears when recounting it.

In 2012, Savita was diagnosed with multiple myeloma in India. After undergoing various treatment methods, her condition relapsed, and doctors estimated she had only six months to live. Desperate and with nowhere else to turn, she decided to seek hope in China.

At the Jiangsu Provincial People’s Hospital North Branch, Savita successfully joined a clinical trial and underwent T-cell therapy. One month after treatment, evaluation results showed that her lesions had almost completely disappeared, indicating significant improvement.

When she was first admitted, Savita was bedridden, suffering from severe bone pain, and required daily injections of strong painkillers. Now, she can live like a healthy person and even went on a trip to Shanghai with her husband, Inder.

Even more joyful is the fact that her daughter will be getting married next January. Reborn with a new lease on life, she is filled with hope for the future, and her joy is palpable.

Savita’s husband, Inder, shared their medical journey in China with a group of multiple myeloma patients in India, and many are hopeful to come to China for treatment.

Ms. Savita’s story is a journey filled with hope and gratitude. She will bring this gratitude back to India, inspiring more people to see the light of hope.

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

WhatsApp: 137 1795 9070

Email: doctor.huang@globecancer.com

#IndianPatient #ChinaTreatment #CancerRecovery #NewLife #Gratitude #MedicalMiracle #LightOfHope

5 months ago patient story , Myeloma

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.

5 months ago patient story

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.

6 months ago Myeloma , patient story

Key Steps in Precision Treatment: A Detailed Overview of CAR-T Infusion for a Russian Patient at Jiahui in Shanghai

Key Steps in Precision Treatment: A Detailed Overview of CAR-T Infusion for a Russian Patient at Jiahui in Shanghai**

Vladimir Borzenkov, a 68-year-old patient from St. Petersburg, Russia, recently completed the core phase of CAR-T therapy—reinfusion—at Jiahui International Hospital in Shanghai. This crucial step involves reinfusing T-cells, which have been genetically modified to recognize and attack specific cancer cells, back into the patient’s body. For Mr. Vladimir, who has been battling his condition for over five years, this step is particularly significant.

Before the reinfusion, the medical team conducted a comprehensive physical assessment to ensure his body could withstand the procedure. Despite being in his sixties, Vladimir’s determination and desire for a cure helped him overcome any obstacles posed by his age. His journey began in December 2017 with back pain, which progressively worsened over several months. By February 2018, multiple bones, including his spine, sternum, and clavicle, showed signs of deterioration. Although this period seemed like a relentless trial, Vladimir never lost his faith in life. Now, at this critical juncture, he is filled with hope for the future.

For this treatment, Jiahui Hospital utilized FUCASO (Eque-cel), a fully human CAR-T therapy known for its unique low immunogenicity and lasting efficacy, providing therapeutic advantages for the patient. During the reinfusion process, Jiahui Hospital demonstrated advanced capabilities in monitoring and managing adverse reactions. The hospital is equipped with the latest monitoring technology and a highly experienced medical team, ensuring that any potential adverse reactions are promptly identified and managed, thus ensuring the safety and effectiveness of the treatment. This high level of monitoring and detailed attention to the patient’s health made Vladimir’s treatment process not only efficient but also safe.

Through his experience at Jiahui International Hospital, Vladimir witnessed the powerful potential of CAR-T therapy and the significant advantages of FUCASO. He is now filled with hope for the future treatment outcomes. This treatment marks not only a significant milestone in his personal battle against cancer but also showcases Jiahui’s expertise in CAR-T technology and excellent patient care.

#CART #MultipleMyeloma #FUCASOJourney #Equecel #JiahuiHospital #Shanghai #CancerSurvivor #bloodcancer #Immunotherapy #FullyHumanCART #CancerTreatment

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Tags Archives: multiple myeloma

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