Write a new chapter in standardized diagnosis and treatment, create an infinite future of MM, and open the MM standardized diagnosis and treatment Sino-foreign exchange series of China-Europe station wonderfully

Multiple myeloma (MM) is a malignant disease with abnormal proliferation of clonal plasma cells with a high degree of heterogeneity, and the survival prognosis of patients is very different
.
Different types of MM patients have great differences
in the choice of treatment regimen and response to treatment.
In order to further improve the standardization of MM diagnosis and treatment, strengthen the whole process management of MM patients to achieve effective treatment and long-term benefits, the "MM Standardized Diagnosis and Treatment Sino-Foreign Exchange Series - China-Europe Station" has been held
online on September 29, 2022.

The conference was chaired by Professor Niu Ting of West China Hospital of Sichuan University, Professor Mattia D'Agostino of the University of Turin, Professor Mi Jianqing of Shanghai Ruijin Hospital, and Professor Zhang Li of West China Hospital of Sichuan University shared
the progress of MM diagnosis and treatment.
Medical Pulse now organizes the wonderful content as follows for the readers!

At the beginning of the conference, Professor Niu Ting, chairman of the conference, said in his opening speech that MM is the second most common malignant tumor in the blood system, MM immunotherapy has made great progress in recent years, and new therapies such as CD38 monoclonal antibody, antibody-conjugated drugs, bispecific antibodies, and chimeric antigen receptor T cells (CAR-T) provide more treatment options for MM, especially in relapsed refractory and high-risk patients
.
This conference focuses on new antibody drugs, invites many experts and scholars at home and abroad to share and exchange innovative experiences, and hopes to burst out a dazzling academic spark through the collision of Chinese and European ideas!

Under the auspices of Professor Mi Jianqing, Professor Mattia D'Agostino shared the effect of chromosome 1q gain/amp (1q+) on
MM.
1q+ is one of the most common high-risk cytogenetic abnormalities in MM patients, with approximately 30% to 50% of newly diagnosed MM (NDMM) patients and 50% to 80% of patients with relapsed/refractory MM (RRMM) may be accompanied by 1q+
.
1q+ is strongly associated with a higher disease burden and poor prognosis, presents many challenges for the treatment of MM, and has a significantly worse
survival prognosis in patients with 1q amp (≥ 4 copy numbers) than in patients with 1q gain (3 copy numbers).
In addition, 1q+ is often associated with other high-risk cytogenetic abnormalities t(4; 14）、t（14; The coexistence of 16) or del (17p) will lead to worse clinical outcomes
than those accompanied by isolated 1q+.
The inclusion of 1q+ in the prognostic assessment system for MM patients has helped optimize risk stratification, and several studies are expanding the definition of high-risk populations with 1q+ and the accompanying ≥ two high-risk cytogenetic abnormalities have also distinguished an ultra-high-risk MM type
with a very poor prognosis.
Staging systems such as the Mayoga Component Phase System (MASS) and the 2nd Revised International Staging System (R2-ISS) confirm that the inclusion of independent adverse prognostic factor 1q+ provides a more accurate predictor
of clinical outcomes.

At present, the clinical data for patients with 1q+MM are limited, and the international authoritative guidelines have not yet made specific treatment recommendations
.
In patients with RRMM, stage III ICARIA-MM and IKEMA studies have shown that combined Isatuximab (Isa-Pd; Isa-Kd) improves outcomes
in patients with 1q+RRMM.
In patients with NDMM, the Phase II FORTE study showed that the KRd protocol induced therapy sequential autologous hematopoietic stem cell transplantation (ASCT) prolongs progression-free survival (PFS) in patients with 1q gain; Data from the Phase II GRIFFIN study suggest that VRd regimens combined with daretoulumab (D-VRd) will increase the negative rate of persistent minimal residual disease (MRD) in patients with 1q+ and bring about long-lasting deep remission; Data from the phase III GMMG-HD7 study suggest that VRd regimens in combination with Isatuximab (Isa-VRd) therapy have higher
MRD-negative rates in patients with 1q+.

*K: carfezomib, P: bortezomib, d: dexamethasone, R: lenalidomide, V: bortezomib

In the "Big Coffee Talk" session, Professor Mattia D'Agostino, Professor Deng Jianchuan of the Second Affiliated Hospital of Chongqing Medical University, Professor Han Xiaoyan of the First Affiliated Hospital of Zhejiang University School of Medicine, Professor Wang Yan of Shanghai Ruijin Hospital, Professor Wei Zheng of Shanghai Zhongshan Hospital, and Professor Zhang Li had a wonderful discussion
。 At present, the research on treatment with 1q+MM is limited, and more prospective clinical trials are urgently needed, and a large number of genes on the 1q chromosome such as the MCL1 gene may be related to high-risk states, all gene mutation sites need to be considered, and some of these targets are currently being verified and potential therapeutic methods are being explored, and other biomarkers such as the PBX1 gene should also be considered as therapeutic targets
.

Under the auspices of Professor Niu Ting, Professor Mi Jianqing analyzed the individualized treatment routes
for patients with different types of RRMM.
The treatment of high-risk RRMM is a difficult problem that clinicians urgently need to overcome, and the definition of high-risk MM has not yet been unified, and most RRMM trials define high-risk cytogenetics as del (17p), t(4; 14) and/or t(14; 16), but contains 1q+ and t (11; 14) A broader definition of indicators such as these may make more sense, and assessing a patient's cytogenetic risk status will help guide treatment decisions
.

Renal impairment is one of the common complications of MM, up to 50% of patients have renal impairment at the time of diagnosis, will affect the patient's treatment benefits, early treatment is the key
to prevent renal function deterioration and improve patient survival 。 Depending on the degree of renal impairment, proteasome inhibitors and immunomodulators may require corresponding dose adjustments, while CD38 monoclonal antibody (Isatuximab and daretosuzumab), Elotuzumab, Belantamab mafodotin, and celinizol show good efficacy and tolerance in patients with renal impairment, and there is no need to adjust the dose
when used.

MM is more common in old age and a large proportion are in a frail state, and elderly and frail MM patients have poorer survival outcomes and are more susceptible to treatment-related toxicities
.
Weakness may be a stronger determining factor
than age in determining treatment outcomes.
Multiple study subgroup analyses have confirmed that the combination of CD38 monoclonal antibody is the preferred treatment for elderly and frail patients, with good tolerance and a similar incidence of adverse events to that of young, non-frail patients
.

The incidence of extramedullary disease in RRMM is about 3.
4%-14%, which is associated with a significant shortening of PFS and overall survival (OS) in patients, where soft-tissue plasma cell tumors can appear in almost any tissue of the body and have a worse
prognosis than osteo-associated plasma cell tumors.
The definition of extramedullary disease is heterogeneous and can be clinically evaluated
by different functional imaging.
Studies have shown that combination regimens based on carfilzomib, Selinisol, and Isatuximab and bispecific antibodies, CAR-T, etc.
may benefit
patients with RRMM with extramedullary disease.

In the "Big Coffee on the Tao" session, Professor Mi Jianqing, Professor Han Xiaoyan, Professor Deng Jianchuan, and Dr.
Yu Zhengyu of West China Hospital of Sichuan University had a wonderful discussion
.
Identifying high-risk and frail patients prior to treatment for accurate treatment of MM is particularly important, and it is recommended that the patient be reassessed for risk factors and frailty after relapse to guide treatment
.
At the same time, care should be taken to distinguish between elderly but not frail and frail patients and to employ different treatment strategies
.
In addition, patients with 3-4 line relapse are more likely to develop extramedullary invasion, and patients with advanced risk factors need to be assessed before treatment to make early prevention, and patients with extramedullary infiltrates can be treated with a comprehensive treatment plan
of CAR-T combined immunotherapy 。 At the same time, ASCT is the first-line standard treatment for MM, and for tolerable patients, Professor Mi is more inclined to perform direct secondary transplantation, which may be better than the effect of remission after relapse and then saving ASCT; With the advent of new therapies such as CAR-T, there is also ongoing discussion on the choice of ASCT-only, CAR-T only, or ASCT combined with CAR-T
.

Subsequently, Professor Zhang Li focused on antibody drugs and described the latest progress in the treatment of MM in the EHA/IMW conference
.
The advent of antibodies has significantly improved long-term patient outcomes and become a key treatment option for
MM.
Monoclonal antibodies, especially CD38 monoclonal antibodies, have shown considerable efficacy and safety, and the combination regimen based on CD38 monoclonal antibodies has become a sharp tool
for the treatment of NDMM and RRMM.
For patients who are not candidates for transplantation with NDMM, the results of the 2022 EHA's newly published MAIA study show that the combination of daretulizumab (DRd) on the Rd basis allows patients to achieve rapid remission on an Rd basis, and treatment time of ≥ 18 months can significantly improve patient survival
, regardless of renal function or cytogenetic risk status.
Steroid-related adverse effects such as infection may affect patient compliance and quality of life and even lead to death, and REST studies have observed encouraging initial efficacy and tolerable safety
of Isa-VRd regimens in patients unsuitable for transplantation of NDMM.
For patients suitable for transplantation with NDMM, the Isa-VRd and D-VRd protocols also showed long-lasting, deep remission and survival benefits
in the subgroup of cytogenetically high-risk patients containing 1q+.

In patients with RRMM, POLLUX and AS studies have shown that a combination regimen based on daretuzumab can lead to PFS benefits and improved
overall response rates for different patient subgroups.
The ICARIA-MM and IKEMA studies suggest significant improvements in clinical outcomes with Isatuximab-based combination regimens, with Isa-Kd regimens achieving the longest proteasome-based inhibitor-based regimens and the highest complete response (CR)/MRD negative rates and showing consistent PFS benefit
across high-risk subgroups.

Dual antibodies such as Teclistamab, Talquetamab, Elranatamab and others are poised to show good anti-tumor activity and safety in clinical trials, and their combination regimens with CD38 monoclonal antibodies are also being explored
.

In the "Big Coffee on the Tao" session, Professor Zhang Li, Professor Wang Yan and Professor Wei Zheng had a wonderful discussion
.
CAR-T and bispecific antibodies are currently popular therapies for MM, and patients generally choose to enroll in clinical trials based on accessibility, of which CAR-T trials have more stringent
screening of enrolled patients.
New drug development often selects new targets, and when patients receive a targeted drug therapy failure, it is basically possible to switch to drugs
that target other targets.
Even if there are crossover targets, which differ in terms of binding strength and promoter, patients may still benefit
from them.

At this point, the meeting came to a successful conclusion
.
Professor Niu Ting, chairman of the conference, concluded that with the vigorous development of immunotherapy, the continuous emergence of innovative drugs, and the active exploration of four-drug combination programs, clinicians hope to allow patients to obtain good disease control after first-line treatment through standardized diagnosis and treatment, thereby improving the long-term survival of patients; It is also hoped that the medical insurance policy will allow more efficient and low-toxicity drugs to "fly into the homes of ordinary people"
.
MM treatment has undergone earth-shaking changes in the past decade, and I believe that the next decade will also usher in a new development! I look forward to all of you climbing the peak and not being afraid of challenges on the road of MM therapy!

Approval number: MAT-CN-2223834

statement

1.
This material is intended to convey cutting-edge information and does not constitute a recommendation or publicity
for any drug or treatment regimen, including those under development.

2.
The information contained in this material should not replace the 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

*Isatuximab has not been approved in Chinese mainland

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