Table 5.

Factors affecting the prognosis/treatment outcomes of MM.

Factors affecting treatment outcomes	Regimen	Treatment outcome/prognosis	Reference
Patients with IGH deletion + ve	Bortezomib and/or thalidomide-based chemotherapy	Patients with deletion showed improved ORR to PAD induction therapy.	[42]
Higher decorin∗ levels in bone marrow plasma	Chemo-based: VAD, MP; novel agents-based: BTD, BTD and cyclophosphamide	H-DCN was linked to improved treatment results and a longer PFS.	[70]
Cytogenetic abnormalities in MM	Bortezomib and non-bortezomib group	Del (17p), t(4; 14), and 1q21 gain are all independent risk factors for MM patients. Patients with these anomalies are more likely to relapse early.	[87]
TNF promoter polymorphisms	Thalidomide and dexamethasone	TNF-alpha238 GA + AA genotypes were significantly linked with improved PFS and OS.	[29]
Heterogeneous chromosome 12p deletion	Thalidomide and bortezomib groups	Patients with the deletion had a low survival rate when treated with either bortezomib or thalidomide.	[74]
PHD finger protein 19/PHF 19 (also known as polycomb‐like protein 3 [PCL3]) expression in multiple myeloma	BDT, BD, Allo-HSCT	Increased PHF19 expression is linked with poor induction therapy response and a negative prognosis of MM.	[88]
Pre-treatment neutrophil/lymphocyte ratio	Conventional and bortezomib-based chemotherapy	Increased NLR is a poor predictive factor in elderly patients and the advanced stages of MM.	[89]
Early monoclonal protein decline pattern	Regular bortezomib-based chemotherapy followed by ASCT	Those with pattern B showed greater PFS and OS than patients with pattern A or C.	[90]
CTLA-4 polymorphisms	PAD, VCD, VTD	CTLA-4 rs733618 GG decreased PFS and OS in MM patients.	[91]
The effect of type 2 diabetes on the survival of MM patients	Chemotherapy/VAD/thalidomide/bortezomib/HDT and HSCT/bisphosphonates	Pre-existing diabetes – higher mortality risk when compared to non-diabetic peers.	[92]
RI in MM patients	(1)Bortezomib-containing regimens (2)Novel agent-based regimen followed by ASCT (3) (4) BCMA (CAR)-T cell therapyBortezomib in combination with dexamethasone (5)Lenalidomide with low-dose dexamethasone	(1)Prognosis was better in the bortezomib groups than the non-bortezomib groups. (2)Severe RI-adverse prognostic factor for survival in NDMM. In individuals with severe RI, bortezomib-based regimens may be the preferable treatment. (3)CAR-T-cell therapy used to treat R/RMM may improve renal function. (4)Bortezomib in combination with dexamethasone is a safe and efficient treatment for NDMM (with RI). (5)Patients with no/mild RI had a longer PFS and OS compared to those with moderate or severe RI.	[40,75] [48] [93] [94] [83]
Hypercalcemia	Bortezomib or the thalidomide-based induction followed by ASCT on two groups (patients with hypercalcemia and patients without hypercalcemia)	The OS was double-fold in the non-hypercalcemia patients compared to the patients with hypercalcemia.	[95]
Elevated LDH	Bortezomib-based induction and ASCT regimen	A poor prognostic factor for MM	[96]
Presence of EMD	(1)Bortezomib and thalidomide groups (2)A 3-weekly daratumumab regimen in R/RMM followed by ASCT (3)Humanized BCMA (CAR)-T cell therapy in R/RMM (4)Glutathione combined with mecobalamin to treat PN in MM (5)Bortezomib treatment in light-chain MM	(1)EMD has a poorer outcome and CR is higher in the bortezomib-containing regimen. (2)Information on EMD is unavailable. (3)CRS and ICANS were significantly greater in EMD patients. Patients with EMD have a poor prognosis. (4)Mortality risk of MM patients with EMD (2.373) was greater than that of non-EMD MM patients. (5)EMD was more common among the light-chain MM compared to other subtypes.	[73] [34] [61,84,85] [97] [68]

Allo-HSCT: Allogeneic hematopoietic stem cell transplantation; ASCT: Autologous stem cell transplantation; BDT: bortezomib–dexamethasone–thalidomide; BCMA: Anti-B-cell maturation antigen; BD: bortezomib–dexamethasone; BTD: Bortezomib–dexamethasone with thalidomide; CAR: Chimeric antigen receptor; CR: Complete response; CRS: Cytokine release syndrome; Cy: Cyclophosphamide; CTLA-4: Cytotoxic T-lymphocyte-associated protein 4; DM: Diabetes mellitus; EMD: Extramedullary disease; H-DCN: High decorin; HDT: High-dose therapy; HSCT: Hematopoietic stem cell therapy; ICANS: Immune effector cell-associated neurotoxic syndrome; IGH: Immunoglobulin heavy chain gene; MM: Multiple myeloma; MP: Melphalan and prednisolone; NDMM: Newly diagnosed multiple myeloma; NLR: Neutrophil/lymphocyte ratio; OS: Overall survival; PAD: Bortezomib–doxorubicin–dexamethasone; PFS: Progression-free survival; PN: Peripheral neuropathy; RI: Renal impairment; R/RMM: Relapsed and refractory multiple myeloma; TNF: Tumor necrosis factor; VAD: Vincristine–doxorubicin–dexamethasone.

∗ It is the only instance, where decorin is mentioned in the review. We have presented the findings from a study (included in this review) which compared decorin with other treatment regimens.