2021 ASH deep ploughs MM, broad extension new disease, Isatuximab research progress express

The American Annual Meeting of Hematology (ASH) is one of the largest and most comprehensive international academic conferences in the field of hematology in the world.
The 63rd ASH Annual Meeting in 2021 will be held both offline and online from December 11th to 14th, focusing on Advanced research on blood diseases and improvement of the level of disease diagnosis and treatment
.

The annual meeting announced a number of articles about the latest research progress of the anti-CD38 monoclonal antibody Isatuximab (ISA).
The editor summarizes the main contents as follows for the reference of readers
.

Application of ISA in patients with newly diagnosed multiple myeloma (NDMM) Oral463 GMMG-HD7 Phase III trial: Efficacy and safety of ISA combined with lenalidomide, bortezomib, and dexamethasone (Isa-RVd) in the treatment of NDMM patients Evaluation>>>>Study Design GMMG-HD7 is a randomized, open-label, multi-center phase III clinical trial.
The enrolled patients are NDMM patients who are suitable for transplantation
.

After enrollment, the patients received 3 cycles (C), each cycle of 42 days (d) of lenalidomide, bortezomib, and dexamethasone (RVd)
.

Patients in the Isa-RVd treatment group received ISA intravenous injection (10mg/kg) on ​​C1d1, 8, 15, 22, 29; C2-3d1, 15, 29
.

The primary endpoint of the study is the negative rate of minimal residual disease (MRD) after induction therapy; secondary endpoints include complete response rate (CR) and safety
.

>>>>Research results From October 9, 2018 to September 2020, 662 patients were enrolled in the study
.

Among them, 293 patients (89.
1%) and 312 patients (94.
3%) in the RVd treatment group and Isa-RVd treatment group, respectively, continued to receive further research treatment after induction therapy
.

Among patients with evaluable efficacy, the negative rates of MRD in the RVd treatment group and Isa-RVd treatment group were 35.
6% and 50.
1%, respectively, the CR was 21.
6% and 24.
2%, and the very good partial response rate (VGPR) was 60.
5, respectively.
% And 77.
3%
.

The incidence of at least one grade ≥3 adverse event (AE) in the RVd treatment group and Isa-RVd treatment group was 61.
3% and 63.
6%, respectively, and the incidence of serious adverse events (SAE) was 36.
3% and 34.
8%, respectively, without significant Difference
.

>>>>Research conclusions Through multivariate analysis, it can be known that combined ISA treatment is the only significant predictor of the increase in the negative rate of MRD
.

Compared with RVd, there was no increase in SAE or early discontinuation rates in patients treated with Isa-RVd
.

The trial is ongoing, including analysis after autologous transplantation, and a second randomization will be carried out in the follow-up to further evaluate the efficacy of Isa-RVd treatment
.

Poster1671 Iril Interim Analysis: Efficacy and safety evaluation of ISA combined with lenalidomide and dexamethasone (Isa-Rd) in patients with poor response to lenalidomide and dexamethasone (Rd) >>>>Research Design Iril is a phase II, multicenter study in which NDMM patients were treated with lenalidomide (25mg d1-d21 28d/cycle) and dexamethasone (40mg/week, 20mg/week for patients ≥75 years old) after enrollment
.

Efficacy evaluation after 4 cycles of treatment <partial remission (PR), or efficacy evaluation after 6 cycles of treatment <VGPR, or efficacy evaluation after 9 cycles of treatment <CR, or patients with disease progression (PD) within 9 cycles of treatment , Combined with ISA (C1 10mg/kg per week, once every two weeks thereafter) treatment until the treatment is terminated due to PD or AE
.

The primary endpoint of the study was the PR rate of patients who failed to achieve PR after 4 cycles of Rd treatment after completing 6 cycles of Isa-Rd treatment
.

The secondary endpoints are the depth of remission, PFS, OS, and the incidence of AE
.

>>>>Research results From June 2019 to June 2021, a total of 42 patients were enrolled, of which 25 patients received ISA intensive treatment
.

18 patients received ISA intensive treatment for more than 6 months, and 66.
7% of the patients had an increase in the depth of remission
.

After 4 cycles of Rd treatment, PR was not achieved.
Among the 9 patients who received ISA intensive treatment, 5 patients achieved PR and 4 patients achieved VGPR
.

Among them, 7 patients received ISA intensive treatment for more than 6 months, and 100% of the patients had an increase in the depth of remission
.

Among the 30 patients with evaluable efficacy in the total cohort, the median follow-up time was 9.
96 months, the ORR was 100% (16 cases of PR, 14 cases of VGPR), and the median OS was not reached
.

The incidence of AE of any grade was 73.
8%, and the incidence of AE ≥3 was 38%
.

>>>>Research Conclusions The results of the study show that regardless of the initial response to Rd, the ORR of patients who can be assessed for efficacy is 100% after ISA intensive treatment
.

Isa-Rd is well tolerated in the cohort of elderly patients, and its safety is not significantly different from previous studies
.

Application of ISA in patients with relapsed/refractory multiple myeloma (RRMM) Poster1963 Real-world study: Efficacy and safety evaluation of ISA combined with pomalidomide and dexamethasone (IsaPomDex) program>>>>Study Design This A retrospective study included RRMM patients who were treated with IsaPomDex at 24 cancer centers in the UK
.

The primary endpoint of the study is the overall response rate (ORR)
.

Secondary endpoints include progression-free survival (PFS), overall survival (OS), and incidence of AEs
.

>>>>Research Results A total of 107 patients were enrolled in the study, with a median age of 69 years.
Among them, 15 patients were at high risk of cytogenetics, and the median number of previous treatment lines was 3
.

The median follow-up time was 3.
7 months, and the median value of the IsaPomDex medication cycle was 4
.

The ORR was 61.
7%.
There was no significant difference in ORR between the subgroup of elderly patients ≥75 years of age and the subgroup of patients with a heavier burden of comorbidity compared with the total cohort
.

The median PFS was 10.
1 months, and the incidence of PFS at 3 months was 82.
4%
.

The median OS was not reached, and the incidence of OS at 3 months was 87.
2%
.

The incidence of AEs at any level was 87.
9%, the incidence of AEs ≥3 was 62.
6%, and the incidence of hematology AEs ≥3 was 53.
2%
.

>>>>Research conclusions The research results show that the ORR and PFS of RRMM patients after treatment with IsaPomDex are equivalent to the data of the ICARIA-MM trial.
AEs can be managed through close monitoring and dose adjustment
.

The study will follow up the enrolled patients for a longer period of time to further evaluate the efficacy and safety of the IsaPomDex program
.

Poster3785 Retrospective analysis: Evaluation of the response rate of patients who have received CD38 monoclonal antibody regimen after re-treatment with CD38 monoclonal antibody >>>> Study design The enrolled patients are MM patients who have previously received CD38 monoclonal antibody therapy.
PFS and OS after receiving another CD38 monoclonal antibody treatment
.

>>>>Research Results A total of 49 patients were enrolled in the study, of which 40 patients had only received Daratumumab (DARA) treatment, 1 had only received ISA treatment, and 8 received both combined treatments
.

After the initial use of the CD38 monoclonal antibody-containing treatment program, the clinical benefit rate (CBR) was 44.
9%, and the ORR was 38.
8%
.

After using the CD38 monoclonal antibody-containing treatment program again, the CBR was 42.
9% and the ORR was 40.
8%
.

The PFS of the patients who used the CD38 monoclonal antibody-containing treatment regimen for the first time and again were 3 months and 5.
9 months, respectively; the median OS was 26.
2 months and 36.
5 months, respectively
.

>>>>Research conclusions The results of the study show that RRMM patients who have received CD38 monoclonal antibody treatment in the past can still respond continuously after receiving another CD38 monoclonal antibody treatment
.

This study provides support for the retreatment of RRMM patients who have previously used CD38 monoclonal antibody-containing regimens
.

Poster1962 ISA combined with carfilzomib, dexamethasone (lsa-Kd) regimen and DARA combined with lenalidomide, dexamethasone (Dara-Rd) regimen in the treatment of RRMM patients indirect comparison>>>>study design will IKEMA III The research data of lsa-Kd (n=179) in the trial (NCT03275285) and the research data of Dara-Rd (n=286) in the POLLUX phase III trial (NCT02076009) were indirectly compared through matching adjustments
.

>>>>The matched data show that the PFS of the lsa-Kd group is significantly better than that of the Dara-Rd group, as shown in Figure 1
.

The OS and VGPR of the lsa-Kd group were better than those of the Dara-Rd group
.

The incidence of patients with constipation, cough, diarrhea, fatigue, febrile neutropenia, muscle cramps, nasopharyngitis, nausea, fever and grade 3-4 diarrhea and febrile neutropenia was significantly lower in the lsa-Kd group In the Dara-Rd group
.

Figure 1 Comparison of PFS between lsa-Kd group and Dara-Rd group after matching>>>>Conclusions of the study Dara-Rd
.

These data show that, compared with the use of Dara-Rd, finalidomide refractory patients can obtain better results with lsa-Kd treatment in the early relapse
.

Evaluation of the efficacy and safety of Poster2744 ISA subcutaneous injection (SC) combined with pomalidomide and dexamethasone (Pd)>>>>Study Design This multicenter, open-label, phase 1b study enrolled patients in the first cycle At that time, ISA was administered once a week for 4 consecutive weeks; in subsequent cycles, it was administered once every 2 weeks
.

The primary endpoint evaluated the safety, the secondary endpoint was ORR, PFS and so on
.

>>>>
The results of the study were 34 patients, including 12 patients with intravenous (IV) ISA-10mg/kg+Pd, 12 patients with SC ISA1000mg/kg+Pd, and 10 patients with SC ISA1400mg+Pd .

The incidence of infusion reaction (IR) was ≤10% in each cohort, and they were all grade 2
.

There were no treatment emergency adverse events (TEAEs) that resulted in death, treatment discontinuation, or premature discontinuation of ISA
.

The ORR of the IV group was 66.
7%, the VGPR was 33%, and the CR was 16.
7%; the ORR of the SC1000 group was 66.
7%, the VGPR was 41.
7%, and the CR was 25%; the ORR of the SC1400 group was 80%, VGPR was 40%, and CR 20%
.

At 8 months, the PFS rates of the IV group, SC1000 group, and SC1400 group were 73%, 73%, and 89%, respectively
.

>>>>Research conclusions The research results show that compared with IV, ISA SC has the same safety and no new safety signals have been found
.

Compared with IV, SC can achieve higher Ctrough (the best predictor of ISA efficacy) after 4 weeks of administration, and optimize the convenience of administration
.

Application of ISA in patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) Oral516 ISAKIDS interim analysis: ISA combined with chemotherapy in the treatment of patients with relapsed/refractory ALL and AML>>>>Study Design ISAKIDS (NCT03860844) is a single-arm, multi-center, open-label Phase II study, including 3 independent cohorts of B-ALL, T-ALL, and AML
.

The age range of the enrolled patients was 2-18 years old.
The enrolled patients received 20mg/kg ISA treatment on the first day, then the ALL group was administered once every 5 weeks, and the AML group was administered once every 3 weeks; the combination was started on the 8th day Chemotherapy
.

The primary endpoint is CR, and secondary endpoints include duration of response (DOR), event-free survival (EFS), OS, and ORR
.

>>>>Research results A total of 24 patients were enrolled (B-ALL group-10 cases, T-ALL group-7 cases, AML group-7 cases)
.

As of May 11, 2021, there are 17 patients whose curative effect can be evaluated: CR of B-ALL group, T-ALL group and AML group were 42.
9%, 33.
3%, and 50%, respectively
.

The incidence of IR was 37.
5%, and the incidence of Grade 5 TEAEs was 12.
5%
.

Preliminary analysis of the PK of 18 patients (>2 years old) showed that the PK parameters of pediatric patients were consistent with those of adult patients
.

>>>>Study Conclusions The results of the study show that 41.
2% (7/17) of patients with poor prognosis have obtained CR
.

There was no significant difference in the incidence of AE and PK parameters compared with adult patients
.

Summary Hematological tumors such as MM, ALL, AML, etc.
are difficult to cure.
Various combination treatments based on Isatuximab have great potential in further improving the effectiveness of treatment
.

With the continuous deepening of research, it is expected to bring new treatment hopes for the majority of hematological tumor patients
.

References: [1] Hartmut Goldschmidt, et al.
2021ASH.
Oral463.
[2] Slavisa Ninkovic, et al.
2021ASH.
Poster1671.
[3] Faouzi Djebbari, et al.
2021ASH.
Poster1963.
[4] David Yashar, et al .
2021ASH.
Poster3785.
[5] Joshua Richter, et al.
2021ASH.
Poster1962.
[6] Philippe Moreau, et al.
2021ASH.
Poster2744.
[7] Andre Baruchel, et al.
2021ASH.
Oral516.
MAT-CN-2132308 statement 1.
This material is intended to convey cutting-edge information, and does not constitute a recommendation or publicity for any drugs or diagnosis and treatment programs (including drugs under development)
.

2.
The information contained in this material should not replace any medical advice provided by medical and health professionals.
For specific disease diagnosis and treatment, please follow the advice and guidance of medical and health professionals
.

Poke "read the original text", we make progress together