I. Overview
Multiple myeloma (MM), a malignant tumor with abnormal proliferation of plasma cells in the bone marrow, is characterized by the secretion of monoclonal immunoglobulins (M proteins). Chemotherapy cannot cure MM, nor can it prevent the transformation and development of monoclonal gammaglobulinemia of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and isolated plasmacytoma. Stage I MM cannot benefit from early treatment, while long-term chemotherapy increases the incidence of secondary leukemia and MDS, and can also lead to immune depression and impairment of organ function, so when myeloma progresses to stage II Therefore, chemotherapy-based systemic therapy should be administered only when myeloma progresses to stage II or above. The aim of systemic therapy is to reduce the tumor load, relieve symptoms, and achieve a stable plateau, mostly using conventional dose chemotherapy with bisphosphonates. High-dose chemotherapy (HDT) ± ASCT is also an option. In addition, it is worth noting that patients preparing for transplantation should not use alkylating agents until their own hematopoietic stem cells are collected.
II. Chemotherapy regimen
1.Conventional dose chemotherapy for primary treatment
The conventional dose chemotherapy regimen for primary treatment includes MP regimen, VAD regimen, DEX regimen, Thal/DEX regimen, DVD regimen, etc.
(1) MP regimen: the standard treatment regimen for MM
MEL 8mg/m2/day Day 1-4
pred 60mg/m2/day Day 1-4
Repeat every 4-6 weeks, total efficiency 40-60%.
(2) Combination chemotherapy based on alkylating agents
①VBMCP/M2 regimen
VCR 1.2mg/m2 /day Day 1 iv
BCNU 20mg/m2 /day day 1 iv
MEL 8mg/m2 /day day 1-4 po
CTX 400mg/m2 /day Day 1 iv
Pred 60mg/m2 /day day 1-14 po
Repeated every 35 days, with an efficiency of about 70%.
②VMCP regimen
VCR+MEL+CTX+Pred
③ABCM regimen
ADM+BCNU+CTX+MEL
(3) VAD and related regimens.
①VAD regimen
VCR 0.4mg/day CT24 hours Day 1-4
ADM 9mg/day CT24 hours Day 1-4
Dex 20mg/m2 /day po Day 1-4 9-12 17-20
VAD regimen remission rate 55-84%, renal insufficiency, hematocrit, need to rapidly reduce the tumor load such as hypercalcemia, renal failure, nerve compression, proposed to collect stem cells for ASCT, VAD regimen can be preferred
②VAD-like regimens.
Replace ADM with other anthracyclines, such as IDA, MIT, liposomal adriamycin (CAELYX).
Substitute Dex with methylprednisone (mePDNL) to reduce corticosteroid-related toxicity.
VAMP (VCR ADM mePDNL).
C-VAMP (CTX added between two courses of VAMP).
VID (VCR IDA Dex).
DVD (CAELYX VCR Dex).
(4) High-dose Dex (HDD)
20mg/m2 /day Days 1-4, 9-12, 17-20, repeated at 14 days interval, 3 courses to evaluate the efficacy, total efficiency 43%, suitable for hypercalcemia, hematocrit, those who need concurrent radiotherapy due to pathological fracture, not applicable to cytotoxic drugs and patients with impaired renal function.
2.Maintenance therapy
For chemotherapy close to complete remission, IgA and light chain type MM should continue maintenance therapy after achieving remission, while other MM entering the stable/plateau stage is controversial whether to carry out maintenance therapy, currently most do not advocate maintenance therapy with cytotoxic drugs, there are reports that corticosteroids and IFN-α can prolong the remission period of some patients.
3.Salvage therapy for refractory relapsed MM
The salvage treatment options for refractory relapsed MM include high-dose Dex, high-dose MEL, high-dose CTX, VAD, VP16-containing regimen, combination of response stop and chemotherapy, bcl-2 antinucleotide, arsenic trioxide, autologous stem cell transplantation, biological therapy, etc.
4.Proteasome inhibitor–Vanco (Velcade)
Proteasome is the main protease that catalyzes protein hydrolysis in the cytoplasm and nucleus. Proteins need to be ubiquitinated via the ubiquitin-proteasome pathway (UPP) before they can be degraded by proteasome. The proteasome in higher eukaryotic cells is the 26S proteasome, which can efficiently and highly selectively degrade intracellular proteins, including cell cycle regulator proteins, tumor suppressor proteins and transcription factors, and is closely related to tumorigenesis and progression. It inhibits the adhesion of MM cells to bone marrow stromal cells, inhibits the production of IL-6 and its transmission between cells, inhibits the production and expression of angiopoietin, and inhibits the expression and action of some other factors related to apoptosis.
Velcade single-agent regimen: 1.3 mg/m2 IV on days 1, 4, 8, 11 for 8 cycles, followed by 2 cycles after complete remission. The efficacy rate was 27%.