Micro Classroom No. 11 Professor An Gang: Guidelines for Integrated Diagnosis and Treatment of Tumors in China (CACA)—MM Integrated Diagnosis and Treatment (MDT to HIM) Overview

"China Cancer Integrated Diagnosis and Treatment Guidelines" 1 is the authoritative experts of the Chinese Anti-Cancer Association (CACA) over a period of more than ¹ year, collectively compiled and completed China's first integrated tumor diagnosis and treatment guidelines, on the basis of reference to the United States NCCN and European ESMO and other international guidelines, especially focusing on the epidemiological characteristics, genetic background, original research results and diagnosis and treatment prevention and control characteristics of the Chinese group, focusing on Chinese characteristics, reflecting integrated thinking, is more suitable for the Chinese group of tumor guidelines

MM is a progressive malignant plasma cell disease, almost all of which arise from asymptomatic monoclonal immunoglobulinemia (MGUS) of unknown significance, which may later progress to smoke-type myeloma (SMM), then into symptomatic MM, and even secondary plasma cell leukemia in advanced stages

Figure 1 Complexity of multiple myeloma disease progression

There are currently three eras

The CACA-MM guidelines emphasize the concept of accurate diagnosis and individualized treatment according to the genetic characteristics of MM patients in China, and fully demonstrate Chinese characteristics; And attach importance to the concept of integrated medicine, give full play to the advantages of internal medicine, pharmacy, traditional Chinese medicine and other disciplines, to achieve the purpose of

Figure 2 Comparison of MM-related guidelines

For patients with different types of MM, the CACA-MM guidelines recommend different treatment strategies

For patients suitable for transplantation, induction therapy is required prior to autologous hematopoietic stem cell transplantation (ASCT) to quickly control tumors, avoid damage to important organs, and create conditions

Whether consolidation therapy is required after ASCT is still controversial
.

Although some studies have shown that consolidation therapy can improve the depth of remission and prolong progression-free survival (PFS), more data
is needed on whether consolidation therapy can prolong OS.

The consolidation of the status of treatment after ASCT is largely affected by the quality of remission of induction therapy
.

Guidelines recommend that patients receiving induction therapy with VCd (bortezomib + cyclophosphamide + dexamethasone) regimen may consider consolidation
using a two-cycle VRd regimen.

With regard to maintenance therapy after ASCT, the use of lenalidomide can bring significant PFS and OS benefits to patients, and bortezomib maintenance therapy every two weeks may be considered in patients who cannot tolerate or receive lenalidomide; For patients at high risk of cytogenetics, PI (bortezomib or isazomib) maintenance therapy should be considered; In ultra-high-risk patients, maintenance therapy
can be performed using a combination of PI and IMiDs.

Regardless of the response after ASCT, maintenance therapy should be continued for at least 2 years
.

The duration of maintenance therapy or the optimal depth of response to discontinuation has not been determined, and future clinical trials may explore whether a minimal residual lesion (MRD) status can be used to guide maintenance therapy
.

For MM patients who are not suitable for transplantation, patients should be stratified according to their physical fitness status, whether there are complications and other factors, and it is recommended to prospectively apply the GA assessment system (Figure 3) to comprehensively assess the patient's physical condition and formulate an individualized treatment plan
in clinical evaluation.

Figure 3 Contents of the GA assessment system for the elderly

For patients with good physical fitness, it is recommended to choose a three-drug combination treatment regimen, the preferred VRd and DRd regimen, and other options include BCd± Dara, D-VMP and IRd regimens; For patients with general physical fitness, it is recommended to use a reduced three-drug combination regimen, or a standard two-drug combination regimen, which can choose VRd-lite, Rd± Dara, IRd, BCd or RCd; For patients with weakness, a two-dose regimen of reduced dose, or optimal supportive therapy, is recommended to reduce chemotherapy toxicity or prevent the interruption of treatment, and the Bd± Dara, Rd± Dara, or Id± Dara may be used
.

*D/Dara: daretosuzumab, V/B: bortezomib, R: lenalidomide, d: dexamethasone, C: cyclophosphamide, M: mafarin, P: prednisone, I: isazomib

Treatment of patients with relapsed/refractory MM (RRMM) should consider a variety of factors
, such as the timing of treatment, the pretreatment regimen, the response and duration of pretreatment, the toxicity of pretreatment, the patient's physical condition, and the patient's bone marrow reserve.

Patients with the first recurrence of MM (FRMM) should aim to maximize remission and prolong PFS
.

The choice of treatment regimen mainly considers two aspects: first, the duration of the first remission, for patients who relapse within 6 months after remission, it is recommended to switch to a different mechanism of drugs; For patients who relapse after 6 months, it is recommended to use the original regimen or switch to a different mechanism of the drug
.

Second, for patients suitable for transplantation, if they have not received a transplant or have been in remission with maintenance therapy after the first transplant for more than 2-3 years, if the treatment is effective after the first recurrence, ASCT can still be considered as part of
salvage therapy.

CACA-MM guidelines for patients with FRMM recommend the selection of different mechanisms of drugs according to whether the patient is resistant to lenalidomide and bortezomib, mainly including CD38 monoclonal antibody, PI and IMiDs, of which a combination regimen based on daretoulumab is recommended in patients with lenalidomide-sensitive/resistant, bortezomib sensitive/resistant, or dual-resistant FRMM
.

For patients with RRMM who have previously received ≥2-line therapy, the primary goals of treatment are to control the disease, reduce symptoms, avoid damage to important organs, and improve quality of life, on the basis of which to achieve maximum relief
.

Salvage therapy requires an individualized regimen with a choice of at least 1-2 non-drug-resistant new drug combinations such as DPd, DKd, KPd, and other options include Selinizol, Belantamab mafodotin, VdT-PACE, bispecific antibodies, CAR-T and BCL-2 inhibitors
.

For patients with secondary plasma cell leukemia or extensive extramedullary plasma cell tumors, a multi-drug combination regimen containing cytotoxic drugs such as the VdR-PACE regimen can be chosen
.

*P: Pomatomide, K: carfezomib, T: thalidomide, P(VdT-PACE): cisplatin, A: doxorubicin, E: etoposide

summary

For transplanted NDMM patients, the CACA guidelines recommend VRd protocols as the preferred protocol, other commonly used protocols include D-VRd, BCD, DRd, etc.
, and in special cases, D-KRd, D-VCd, D-VTd and other schemes
can be selected.

For NDMM patients who are not suitable for transplantation, it is recommended to choose the treatment plan according to the physical fitness status: VRd and DRd options are preferred for patients with good physical fitness, VRd-lite, Rd± Dara and other options are selected for patients with general physical fitness, and BD, Rd and other options
are available for patients with weak conditions.

In the choice of treatment regimen for patients with first relapse, CACA guidelines recommend the selection of different mechanism drugs according to the patient's resistance to lenalidomide and bortezomib, mainly including monoclonal antibodies, PI and IMiDs
.

Patients with multi-line relapse require individualized treatment, and can choose DPd, DKd, KPd regimens, or selinisol, bispecific antibodies, CAR-T and other treatment options
.

Patients with MM at any stage should fully evaluate their treatment goals and pursue individualized treatment before giving treatment
.

Chinese Anti-Cancer Association.
Guidelines for the integrated diagnosis and treatment of tumors in China.
2022.

EM-110399  Content Approved Date ：9/15/2022

For the reference of medical pharmacy professionals only, reproduction and dissemination are strictly prohibited

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