2021ASH Professor Chen Wenming: The primary endpoint of the GMMG-HD7 phase III trial has been reached, and the MRD-negative rate of Isa-RVd in the treatment of NDMM patients exceeds 50%

The 63rd American Society of Hematology Annual Meeting (ASH) in 2021 will be held both offline and online from December 11th to 14th
.

At this annual meeting, the latest progress of the GMMG-HD7 phase III trial of the efficacy and safety of the ISA combined regimen in the treatment of newly diagnosed multiple myeloma (NDMM) patients was announced.
Professor Chen Wenming from the hospital explained it! Oral 463 GMMG-HD7 phase III trial: Efficacy and safety evaluation of ISA combined with lenalidomide, bortezomib, and dexamethasone (Isa-RVd) in patients with NDMM
.

Research Background For NDMM suitable for transplantation, the RVd regimen is one of the most widely used combination regimens.
On the basis of the RVd regimen, the combination of anti-CD38 monoclonal antibody (CD38-moAb) can improve the curative effect.
GMMG-HD7 is a randomized, open-label study.
The first primary endpoint of the label, multicenter Phase III clinical trial was minimal residual disease (MRD) negativity after induction therapy with RVd and Isa-RVd in transplant-eligible NDMM patients
.

Study Design Transplant-eligible NDMM patients at 67 treatment centers in Germany were randomized 1:1 to RVd and Isa-RVd groups (Figure 1)
.

Stratified according to the Revised International Staging System (R-ISS)
.

The first primary endpoint of the study was the MRD (threshold 1x10-5) negativity rate after induction therapy
.

Secondary endpoints included complete remission (CR) rate and safety after induction therapy
.

Figure 1.
Results of the GMMG-HD7 trial design.
From October 2018 to September 2020, a total of 662 patients were enrolled in the study, with a median age of 58 (range 26-70) years, of whom 660 patients were eligible for the intention-to-treat analysis conditions, the baseline characteristics of patients in different treatment groups were not significantly different (as shown in Table 1)
.

Table 1 Baseline characteristics of patients in the Isa-RVd and RVd groups MRD-negative rates after induction therapy were 35.
6% and 50.
1% in the RVd and Isa-RVd groups, respectively (Fig.
2), and in all subgroups, Isa-RVd induced The negative rates of MRD after treatment were all higher than those of RVd (as shown in Figure 3)
.

Multivariate analysis showed that combined ISA treatment was the only significant predictor of increased MRD-negative rates
.

Fig.
2 MRD-negative rate after induction therapy in Isa-RVd group and RVd groupFig.
3 MRD-negative rate in each subgroup after induction therapy with RVd and Isa-RVd Comparison of CR rate and ≥VGPR rate after induction therapy in Isa-RVd 24.
2% vs 21.
6%; 77.
3% vs 60.
5% in the RVd group and the RVd group, respectively (Figure 4)
.

Figure 4.
In terms of safety of remission rate after induction therapy in Isa-RVd group and RVd group, 63.
6% and 61.
3% of patients in Isa-RVd group and RVd group had at least one adverse event (AE) of grade ≥3, respectively
.

The incidence of serious adverse events (SAEs) in the two groups was 34.
8% and 36.
3%, respectively (Table 2), and the number of patients who discontinued induction therapy due to AEs was comparable in the two groups
.

Table 2.
AE occurrence in patients in Isa-RVd and RVd groups.
Conclusions The GMMG-HD7 trial met the first primary endpoint, confirming that Isa-RVd has a significantly higher rate of MRD negativity
.

There was no increase in SAE or early discontinuation rates in patients treated with Isa-RVd compared with RVd
.

The trial is ongoing and will further evaluate the effect after autologous transplantation, as well as secondary randomization to evaluate the efficacy of ISA combined with lenalidomide maintenance therapy
.

Experts commented that the three-drug combination regimen of proteasome inhibitors, immunomodulators and glucocorticoids is the standard induction therapy for newly diagnosed transplant patients to reduce tumor burden and restore organ function as soon as possible
.

Combining monoclonal antibodies (such as anti-CD38 monoclonal antibody) on the basis of VRD and VTD can further improve the efficacy before transplantation
.

In general, the depth of remission with induction therapy has an impact on the prognosis of post-transplant patients
.

The deeper the remission with induction therapy, the longer the progression-free survival (PFS) and even the overall survival (OS) after transplantation, especially in patients with negative MRD
.

GMMG-HD7 is the first phase III clinical trial to assess the rate of MRD negativity at the end of induction therapy with Isa-RVd in NDMM patients
.

The results of the study showed that the MRD-negative rate of Isa-RVd at the end of 18-week induction therapy was 50.
1%, which was significantly better than the VRd regimen.
It was the induction regimen with the highest MRD-negative rate in all relevant randomized clinical trials so far, and its tolerance Good, the number of patients discontinuing induction therapy due to AEs was comparable between the two groups
.

The Isa-RVd regimen can be used as a preferred regimen for NDMM patients who are suitable for transplantation, and has a good application prospect
.

Professor Chen Wenming Second Chief Physician, Professor and Doctoral Supervisor Director of the Department of Hematology, Beijing Chaoyang Hospital Affiliated to Capital Medical University Member of the Myeloma Working Group (IMWG), Member of the Standing Committee of the Asian Myeloma Network (AMN), Chairman of the Hematology Professional Committee of the Chinese Medical Education Association, Deputy Head of the Plasma Cytology Group of the Hematology Branch of the Chinese Medical Association Deputy Chairman of the Expert Committee Deputy Leader of the China Autologous Stem Cell Transplantation Working Group Member of the Standing Committee of the Hematology and Tumor Branch of the China Anti-Cancer Association and Deputy Director of the Myeloma Special Committee Member of the Standing Committee of the Anti-Leukemia Expert Committee of the Chinese Society of Clinical Oncology Member of the Standing Committee of the Society of Hematology Branch Member of the Hematopoietic Stem Cell Transplantation Group of the Hematology Branch of the Chinese Medical Association Member of the Hematopoietic Stem Cell Transplantation Group of the Chinese Society of Rehabilitation Medicine has successively received more than 10 grants from 2 major national science and technology projects, the National Natural Science Foundation of China, and the Beijing Natural Science Foundation, and published academic papers.
More than 260 papers
.

Edited 3 monographs, edited 2 textbooks, edited 1 monograph, participated in editing 2 textbooks, and participated in editing 2 monographs.
References[1]Hartmut Goldschmidt, et al.
2021ASH.
Oral463.
[2]Gu J, Liu J , Chen M, et al.
Longitudinal Flow Cytometry Identified “Minimal Residual Disease” (MRD) Evolution Patterns for Predicting the Prognosis of Patients with Transplant-Eligible Multiple Myeloma[J] Biol Blood Marrow Transplant.
2018;24(12):2568– 2574.
doi: 10.
1016/j.
bbmt.
2018.
07.
040.
MAT-CN-2200002 Related readings 1.
2021 ASH | Deeply cultivating MM, expanding new diseases, Isatuximab research progress express statement 1.
This material is intended to convey cutting-edge information and does not constitute a pair of Recommendations and advocacy of any drug or treatment regimen, including drugs in development
.

2.
The information contained in this material should not be used as a substitute for medical advice provided by any medical and health professional.
Please follow the advice and guidance of medical and health professionals for the diagnosis and treatment of specific diseases
.

Click "read the original text", let's make progress together