BCMA CAR-T Therapy! Baishi Meishi Guibaoide-cel treatment of multiple myeloma: deep lasting relief, improve the quality of life!

December 08, 2020 / -- BMS and partner Bluebrid Bio recently released the latest data at the 62nd annual meeting of the American Society of Hematology (ASH).
long-term data from the Phase I CRB-401 study showed that patients with relapsed or resuscable multiple myeloma (RRMM) showed sustained depth and lasting remission, with a medium total survival period (OS) of 34.2 months.
data from the Key Registry Phase II KarMMa study show that ide-cel has clinically significant benefits for health-related quality of life and highlights the potential value of ide-cel in older RRMM patients and high-risk RRMM patients.
ide-cel is a B-cell mature antigen (BCMA)-oriented chilayer antigen recipient (CAR) T-cell therapy that is under review by U.S. and European regulators for RRMM adult patients who have previously received at least three therapies, including immunomodulants, protease inhibitors, and anti-CD38 antibodies.
in the United States and the European Union, ide-cel was awarded breakthrough drug eligibility (BTD) and priority drug eligibility (PRIME), respectively.
results from the CRB-401 study: In the Phase I CRB-401 study, 62 RRMM patients who had previously received multiple therapies received idea-cel treatment at six CAR-positive T-cells in doses of 50, 150, 450, 800×10.
end points are safety, and secondary and exploratory endpoints include mitigation rates, progression-free lifetime (PFS), total lifetime (OS), and micro-residual disease (MRD).
security is consistent with previously reported CRB-401 results.
most common adverse events were neutral granulocyte reduction (92%), cytokine release syndrome (CRS, 76%), anemia (76%) and plateiac reduction (74%).
the most common 3/4 adverse events were neutral granulocytic reduction (89%), leectal reduction (61%), anemia (57%) and platerocyte reduction (57%).
most CRS events are level 1 or 2.
4 patients (7%) had Level 3 CRS;
the study, the total remission rate (ORR) was 76% out of 62 patients treated with ide-cel, of which 24 patients (39%) received full remission (CR).
The medium mitigation duration (DoR) is 10.3 months.
PFS was 8.8 months, the middle OS was 34.2 months, and the medium follow-up time was 14.7 months.
these results continue to demonstrate the potential of ide-cel to provide deep, long-lasting remission for overtreatment of RRMM patients, with the potential to address significant unseconded medical needs in such patients.
-KarMMa Study Analysis: Subgroup analysis of outcomes in high-risk and elderly RRMM patients and health-related quality of life analysis showed that ide-cel showed deep and lasting remission in RRMM patients who had been on class 3 drugs.
subgroup analysis of patients with poor prognosis (including myeloid disease, high-risk cytogenetics, high tumor burden) was performed to assess the therapeutic effect of ide-cel at the target dose level of 6 car-positive T cells at 150-450×10.
analysis of 128 patients, ide-cel showed deep, lasting relief in most subgroups, including those at highest risk.
orR and CR in most high-risk sub-groups were ≥ 65% and ≥ 20%, respectively.
, in most high-risk subgroups, the DoR median > 9.2 months and the PFS median > 7.5 months.
a separate subgroup analysis of elderly patients to assess the results of the ide-cel treatment.
multiple myeloma is most common in the elderly, with a medium age of 69 at the time of diagnosis.
has been shown to have a negative impact on prognosmation and limit treatment options.
of the 128 patients treated withide-cel in the KarMMa study, 45 (35%) were patients aged ≥65 and 20≥ (16%) were 70 years old.
rate was compared and consistent with the overall population treated at all target dose levels in the 2 age groups, with ORR of 84-90% and CR of 31%-35%.
same time, the median DoR (age ≥65 years of age 10.7 months and ≥70 years of age patients of 11.0 months) was similar to the median DoR in the overall group of patients treated with the disease.
PFS ≥ 8.6 months (95% CI: 4.9-12.2) and 10.2 months (95% CI:3.1-12.3) for patients aged ≥70 years).
addition, no new safety signals were observed.
analysis of the impact on health-related quality of life (HRQoL) measurements in RRMM patients, ide-cel was associated with clinically meaningful quality of life (QoL) without compromising any HRQoL domain.
From baseline examination to the 3rd and 15th months of the study, most of the patients' functional and symptom scores improved clinically, and different sub-scales achieved statistical significance at various points throughout the follow-up period.
ide-cel is the world's first BCMA CAR-T cell therapy to enter the regulatory review process, based on the principle of embedding BCMA receptors on a patient's T-cells, the preparation process is: from each patient's blood to isolate the T-cells, the use of BCMA antigen receptor-coded trovirus vector modification of T-cells, so that T-cell surface expression BCMA receptors.
treatment, MM patients are pretreated with two chemotherapy drugs (cyclophosphamide and fluorodalabin) to kill the patient's existing T cells, and then infusion bb2121, and once infused back into the patient, ide-cel begins to look for and kill cells expressing BCMA.
ide-cel is part of a joint development, co-promotion and profit-sharing agreement between Shishi Shiguibo and Bluebird Creatures.
integrated clinical development projects for both parties include a number of clinical studies (KarMMa-2, KarMMa-3, KarMMa-4) for early treatment MM, including new MM.
In addition to ide-cel, BMS and Bluebird Bio are also developing the second generation ante-BCMA CAR-T therapy bb2127, a product further developed on the basis of the first generation of CAR-T-ide-cel, which combines a PI3K inhibitor signal to produce a CAR-T product rich in "memory T cells", a longer-lived, more effective group of T-cells with improved tumor resistance.
multiple myeloma (MM) is the second most common hematological malignancy after non-Hodgkin's lymphoma.
recent years, despite significant progress in chemotherapy, protease inhibitors, immunomodulant salidamine derivatives and CD38 targeted antibodies, almost all patients eventually relapse.
, there is an urgent need for new treatment options.
MM market is expected to reach $29 billion by 2027.
BCMA as the target in the study of MM immunotherapy (source literature - PMID: 31277554) B cell mature antigen (BCMA) is an extremely important B cell biomarker, widely found on the surface of MM cells, in recent years has become MM and other blood system malignant tumors of a very popular immunotherapy target.
Currently, there are more than 20 immunotherapies developed for BCMA, mainly divided into three categories: chime antigen-treated T-cell therapy (CAR-T, BMS/Bluebird Biology, Novarma representative), dual-specific antibodies (BsAb, represented by Amgen), antibody drug coupleds (ADC, represented by GlaxoSmithKline).
August, GlaxoSmithKline (GSK) BCMA Targeted Antibody Drug Association (ADC) Blenrep (Belantamab Mafodotin, GSK2857916) won the U.S. and EU approval for the treatment of patients with relapsed or refractic multiple myeloma (R/R MM) who have previously received a variety of therapies, including an immunomodulant, a protease inhibitor, and an anti-CD38 antibody.
it's worth noting that Blenrep is the world's first approved BCMA targeted therapy.
data from the Key Phase II DRAMM-2 study show that in R/R MM patients with past overtreatment (median treated: 7) Blenrep 2.5mg/kg dose The total mitigation rate (ORR) of the group was 31% (n=30/97) and the ORR of the 3.4 mg/kg dose group was 34% (n=34/99), and the data were clinically significant.
data from the DRAMM-1 study show that in BCMA-positive R/R MM patients, the ORR treated by Blenrep reached 60%.
origin: Bristol Myers Squibb and bluebird bio Data Highlighting Anti-BCMA CAR T Cell Therapy, Ide-cel, in Relapsed and Refractory Multiple Myeloma at ASH 2020<!--/ewebeditor:page->