2021EHA Big Coffee Comment on Professor Li Juan: Frontier and Hot Spots of Newly Diagnosed Multiple Myeloma

The 26th European Society of Hematology (EHA) Annual Meeting will be held in the form of an online conference on June 9-17, 2021.
Part of the upcoming report of the conference has been announced in advance
.

Among them, the research results in the field of multiple myeloma (MM) have aroused widespread concern in the industry
.

【Yimaitong】A selected summary of the latest progress of newly diagnosed multiple myeloma (NDMM), and invited Professor Li Juan from the First Affiliated Hospital of Sun Yat-sen University to give a wonderful interpretation
.

[LB1901] The 5-year follow-up OS data of the MAIA study reported that the MAIA Phase III study included 737 NDMM patients who were not suitable for high-dose chemotherapy and autologous stem cell transplantation (ASCT) due to age ≥65 years or comorbidities, and evaluated receiving daratuoma Effectiveness and safety of anti-, lenalidomide, dexamethasone (D-Rd) (n=368) or lenalidomide and dexamethasone (Rd) (n=369) treatment
.

After a median follow-up of nearly 5 years (56.
2 months), it was observed that compared with Rd, D-Rd significantly reduced the risk of death by 32%; the median OS of the two groups did not reach (NR), and 5 patients in the D-Rd group The annual OS rate is 66.
3%, and the Rd is 53.
1%
.

The median PFS of the two groups were NR and 34.
4 months respectively (p<0.
0001)
.

The 5-year PFS of patients in the D-Rd group was 52.
5%, and the Rd was 28.
7%
.

The overall response rate (ORR) of the D-Rd group was 92.
9%, while that of the Rd group was 81.
6% (p<0.
0001)
.

Figure 1: Median PFS and OS of DRd vs Rd.
No new adverse events occurred during longer follow-up
.

The most common grade 3-4 adverse events in the D-Rd/Rd group (incidence rate >15% in either group) were neutropenia (54.
1%/37.
0%), pneumonia (19.
2%/10.
7%), Anemia (16.
8%/21.
6%) and lymphopenia (16.
5%/11.
2%)
.

[Oral180] CASSIOPEIA study: Compared with the observation group, patients who are suitable for transplantation of NDMM after induction/consolidation therapy have a higher MRD-rate of maintenance therapy with daratumomab, and the PFS is longer.
The second part of the CASSIOPEIA Phase III study was included in the Part 1 The 886 patients who achieved ≥ partial remission (PR) who were suitable for transplantation of NDMM were randomly divided into 1:1 groups
.

Received daratumomab (DARA) once every 8 weeks for maintenance treatment for 2 years (n=442) vs observation (OBS) (n=444) until disease progression
.

The results of the study with a median follow-up of 35.
4 months showed that the median PFS of the DARA maintenance treatment group was not reached, and that of the OBS group was 46.
7 months (p<0.
0001).
The median TTP of the DARA maintenance treatment group was not reached, and that of the OBS group was 46.
7.
Months (p<0.
0001), the rate of ≥CR was higher in the DARA maintenance treatment group (72.
9% vs 60.
8%; p<0.
0001)
.

Among patients with ≥CR, minimal residual disease negative (MRD-) in the DARA maintenance treatment group was 58.
6%, and 47.
1% in the OBS group (p=0.
0001)
.

In addition, DARA maintenance treatment was well tolerated, and there were no new signs of adverse events
.

Figure 2: Efficacy of DARA maintenance group vs.
observation group [Oral181] D-CVRd induces and enhances ASCT in the treatment of UHiR NDMM and PCL.
The OPTIMUM/MUKnine study included 107 UHiR NDMM patients during 2017-2019, aiming to observe the central molecule Screening was identified as ultra-high risk newly diagnosed multiple myeloma (UHiR NDMM) and plasma cell leukemia (PCL) patients, using daretuzumab + cyclophosphamide + bortezomib + in the risk stratification clinical trial Nallidomide + dexamethasone (Dara-CVRd) induced and used enhanced high-dose melphalan (HDMEL) and ASCT treatment of NDMM UHiR and PCL patients with treatment response rate and MRD negative rate
.

The results of a median follow-up of 22.
2 months showed that after the induction treatment, the ORR of the intention-to-treat population was 94%, CR was 22%, VGPR was 58%, PR was 15%, PD was 1%, and MRD- was 41%; After 100 days, ORR was 83%, CR was 47%, VGPR was 32%, PR was 5%, PD was 7%, and MRD- was 64%
.

The response rate of PCL patients 100 days after transplantation is relatively low (CR is 22%, VGPR is 22%, PR is 22%, PD is 22%)
.

The most common grade 3/4 adverse events during induction therapy were neutropenia (21%), thrombocytopenia (12%), and infection (12%).
The grade 3 neuropathy rate was 3.
7%
.

[Poster1015] In NDMM patients receiving PIs+/-IMiDs induction therapy, HDT-AHCT early intensive consolidation therapy improved PFS compared with SDT.
This study included IFM 2009, EMN02 / HOVON 95, RV-MM-EMN-441, RV -Randomization of MM-PI-209 and FORTE 5 standard-dose therapy (SDT) and high-dose chemotherapy-autologous hematopoietic cell transplantation (HDT-AHCT) based on proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiD) Systematic review and meta-analysis of controlled trials (RCT)
.

The results show that compared with SDT, the use of HDT-AHCT for early intensive consolidation therapy can bring better PFS, and PFS benefits in both high-risk and standard-risk patients
.

Among the three RCTs (EMN02/HOVON95, RV-MM-EMN-441 and RV-MM-PI-209) subgroups reported OS of patients in the high-risk group.
The analysis showed that compared with standard-risk patients, early HDT-AHCT The benefit of OS in high-risk patients is greater
.

[Poster1025] MRD can be used as a potential surrogate endpoint for PFS in clinical trials of NDMM patients.
75 RCT studies reporting ORR, CR, sCR or MRD and median PFS were included to analyze the correlation between PFS and ORR, CR, sCR or MRD And substitutability, and conduct a review analysis of the relationship between MRD and survival prognosis in 20 RWE studies
.

The results showed that PFS and ORR (r=0.
59), CR (r=0.
48), sCR (r=0.
68) and MRD (r=0.
69) had a moderate to strong significant correlation
.

The unadjusted analysis model estimates that for every one percentage point increase in ORR, CR, sCR, and MRD, the median PFS will increase by 0.
50, 0.
42, 1.
05, and 0.
35 months, respectively
.

After adjusting the ORR and CR parameters, the correlation was still significant.
The systematic review of RWE showed that 20 studies analyzed the correlation between survival and MRD, and 12 of them found that survival was significantly correlated with MRD (p<0.
05)
.

Figure 3: Correlation analysis of PFS and ORR, CR, sCR or MRD [Poster1270] ASCT is an effective, safe and feasible treatment for patients with severe renal injury in MM.
The retrospective single-center study included a median age of 54 years (19-65) 64 years old MM patients with renal failure and receiving ASCT treatment
.

According to whether ASCT depends on dialysis grouping, the complications and blood transfusion requirements of patients with renal failure after ASCT are analyzed
.

Group A were patients who did not undergo dialysis during ASCT (n=54), and group B were patients who were dependent on dialysis during ASCT (n=10)
.

The results showed that the reactivation rate of herpes virus infection in group B was higher than that in group A (30% vs 6%, p=0.
04), and the incidence of reversible toxic encephalopathy was higher (20% vs 0%, p=0.
02 ), the demand for red blood cell transfusion is significantly greater (100% vs 37%, p=0.
001)
.

100 days after ASCT, the patient’s ORR increased from 91% to 96%, CR increased from 45% to 64%, and complete renal remission increased from 28% to 34%, but the total renal remission rate was still within 80%
.

At the time of diagnosis, 23 patients who depended on renal replacement therapy received induction therapy + ASCT, and 14 patients (61%) no longer depended on hemodialysis
.

At a median follow-up of 48 months, the 5-year OS rate was 70%, and the 5-year PFS rate was 42%
.

Figure 4: Comparison of the remission rate before and after transplantation in patients with severe renal impairment of MM.
Expert comment.
In recent years, the research of new drugs for the treatment of MM has been very rapid.
The successive application of proteasome inhibitors, immunomodulators, monoclonal antibodies and other drugs can be used by doctors.
"Weapons" are increasing
.

How to "perform and combine" these "weapons" to maximize their value is the most concerned issue for clinicians
.

This EHA conference announced a number of clinical trials of NDMM, which can bring some enlightenment to the clinical practice of hematologists
.

The results of the 5-year follow-up of the MAIA study showed that compared with Rd, D-Rd treatment is not suitable for transplantation of NDMM patients can reduce the risk of death by 32%
.

The CASSIOPEIA study further proves that daratumomab has significant benefits in all aspects of NDMM patient induction therapy, consolidation therapy, and maintenance treatment.
It is believed that the application of daratumumab in future clinical practice One step in advance, so that good medicine can exert the greatest value and benefit more MM patients
.

Researchers began to pay more attention to the difficult issues in the field of MM
.

In recent years, more and more recent results have been published on the biological characteristics of MM, the improvement of prognostic stratification, the treatment of patients at high risk of early recurrence, and the treatment of patients with severe complications
.

Many articles in this EHA conference have explored these issues
.

In terms of disease prognosis, researchers pay more attention to whether MRD can be used as a potential surrogate endpoint for PFS in clinical trials of NDMM patients
.

In the treatment of special populations, D-CVRd five-drug combination induction therapy and enhanced ASCT treatment UHiR NDMM and PCL have achieved a higher remission rate, which provides ideas for the treatment of this part of patients in clinical practice; for high-risk patients with early relapse, Large-dose pretreatment programs and transplantation consolidation therapy may bring higher OS benefits; in addition, transplantation is also an effective, safe and feasible treatment for patients with severe kidney injury in MM
.

Prof.
Juan Li, second-level professor of Sun Yat-sen University, first-level chief physician, doctoral supervisor, director of the Institute of Hematology, Sun Yat-sen University, a famous doctor of Sun Yat-sen University, director of the Department of Internal Medicine, Sun Yat-sen First Hospital, and director of the Department of Hematology, Guangdong Provincial Physician Association, Guangdong Province Former Chairman of the Hematology Branch of the Provincial Medical Association Chairman of the Hematology Professional Committee of the Guangdong Health Management Society Member of the Standing Committee of the Hematology Branch of the Chinese Medical Association, Leader of the Plasma Cell Diseases Group Member of the Standing Committee of the Hematologist Branch of the Chinese Medical Doctor Association, multiple myeloma Hematology Professional Committee of the Chinese Women Physicians Association, Hematology Professional Committee of the Cross-Strait Medical and Health Exchange Association, Hematology Branch of China Medical and Health International Exchange Promotion Association, Hematology Professional Committee of China Medical Education Association, Vice Chairman of Hematology Professional Committee of China Medical Education Association, Chinese Geriatrics Member of the Standing Committee of the Society of Hematology, the International Myeloma Association and the Asian Myeloma Network, have hosted or are hosting more than 20 funds including the National Natural Science Foundation.
More than 200 papers have been published as the first author or corresponding author, and more than 70 papers have been included in SCI.
As the first person in charge, he won the first and third prizes of Guangdong Science and Technology Progress, the second prize of China Medical Award, and edited 6 monographs
.

References: 1.
Thierry Facon,et al.
2021EHA:LB1901.
2.
Philippe Moreau,et al.
2021EHA:Oral180.
3.
Martin Kaiser,et al.
2021EHA:Oral181.
4.
Samiksha Gupta,et al.
2021EHA:Poster1015 .
5.
Patrick Daniele,et al.
2021EHA:Poster1025.
6.
Maiia Firsova,et al.
2021EHA:Poster1270.
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