**3. Goal of treatment**

The overall goal of treatment of MM is to improve survival [14, 15]. A complete response (CR) has been observed only in few patients with conventional chemotherapy regimens. The use of high-dose therapy followed by ASCT and the advent of novel therapies, such as thalidomide, lenalidomide, and bortezomib gained much promises [14, 15], and with such treatment many patients are gaining the much needed improvement and CR. Studies reported that the success of CR correlates with

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*Treatment Approaches of Multiple Myeloma DOI: http://dx.doi.org/10.5772/intechopen.97390*

**4. Management of newly diagnosed cases**

of upfront versus delayed ASCT [9].

clinical practice [19].

VTD (DaraVTD) [21].

dexamethasone (Rd), (**Figure 1**) [22].

survival, and hence the role of CR as an endpoint in myeloma therapy is becoming prominence. It should also be noted that the benefit of CR is not the same with all treatment regimens [15, 16]. Emerging evidence with novel medications showed that

Currently, for fit newly diagnosed MM patients (NDMM), autologous stem cell transplant (ASCT) considered as the standard care of treatment. But it should be noted that there is also a remarkable results obtained from the non-transplant setting with novel agent-based treatment, which later raised questions as to the role

Numerous rescue alternatives that incorporate distinctive combinations of medicines have been developed after the emergence of 2nd generation PIs and IMIDs, monoclonal antibodies (MAs), histone deacetylase inhibitors (HDIs), and, more as of late, check-point inhibitors (CPIs) and small molecules [17, 18]. These promising improvement requests a critical evaluation of treatment options to adequately top up the advantages of different induction, consolidation and maintenance approaches, and to set, a treatment ground so as to compare forthright ASCT,

Several drugs have shown promising activity against MM and are being used in

For patients with ASCT-eligible newly diagnosed MM, induction therapy with triple drugs should contain an IMiD, a PI, and a corticosteroid (Cs), usually lenalidomide-bortezomib-dexamethasone (RVd) [20]. The preferred induction therapy is combination of bortezomib with lenalidomide or thalidomide and dexamethasone (VRd or VTD), as well as the combination of daratumumab with

For patients presenting with renal impairment, cyclophophosphamidebortezomib-dexamethasone is preferred, with the option to switch to RVd up on improvement of renal function. For patients intolerant to the triple therapy, double therapy can be used such as bortezomib-dexamethasone (Vd) and lenalidomide-

Induction treatment can be administered for an extended period for up to 6–8 cycles [23]. A third drug can be added up on improvement of the patient started with two drugs. Recent data with carfilzomib-lenalidomide-dexamethasone (KRd) induction has shown much promise, and ongoing studies comparing the upfront

Looking at the options of the novel triple (or quadruple) upfront Vs postpone for NDMM patients, it is widely advised that mobilization, stem cell harvest, conditioning and ASCT should be postponed due to the fear of immunosuppression in the upfront [25]. In patients receiving daratumumab and or lenalidomide-based induction, stem cell harvest without ASCT can be considered so as to achieve an adequate stem cell yield [8]. In this case, Granulocyte colony-stimulating factor (G-CSF) only mobilization with the potential addition of plerifaxor should be considered in order to avoid the immunosuppressive effect of high-dose cyclophosphamide. However, in cases of viral supra-infections like COVID-19, stem cell harvests and any transplant procedures should not be performed within at least 14,

KRd versus RVd have shown equivalent outcomes, if not improved [24].

and preferably 21, days from the last contact (**Table 1**) [8].

salvage ASCT and allotransplant in the era of novel agent [9].

**4.1 Induction therapy for ASCT-eligible patients**

continued treatment has resulted in prolong CR and improved response [16].

*Multiple Myeloma*

Daratumumab-Pomalidomide-Dexamethasone (DPd)

Elotuzumab-Lenalidomide-Dexamethasone (ERd)

Ixazomib-Lenalidomide-Dexamethasone (IRd)

*can be instituted between cycles.*

*day 1 should be 20 mg/m2*

*newly diagnosed patients.*

*between cycles as done in total therapy protocols.*

*Major treatment regimens in multiple myeloma [9, 10].*

*a*

*b*

*c*

*d*

*e*

**Table 1.**

**Regimen Usual dosing schedulea**

every

Daratumumab 16 mg/kg intravenously weekly 3 8 weeks, and then

Dexamethasone 40 mg intravenous days 1, 8, 15, 22 (given oral on days

Lenalidomide-Dexamethasone repeated in usual schedule every 4 weeks

subcutaneous days 1, 8, 15

 *on days 1, 8 and 15 every 28 days (cycle 1,* 

10 mg/ kg intravenously weekly × 8 weeks, and then every 2 weeks

2 weeks for 4 months, and then once monthly Pomalidomide 4 mg oral on days 1–21

when no daratumumab is being administered)

Repeated every 4 weeks

Repeated every 4 weeks Panobinostat-Bortezomibb Panobinostat 20 mg oral three times a week 3 2 weeks Bortezomib 1.3 mg/m2

Repeated every 3 weeks

*Doses of dexamethasone and/or bortezomib reduced based on other data showing lower toxicity and similar efficacy with reduced doses; subcutaneous route of administration of bortezomib preferred based on data showing lower* 

*The day 22 dose of all 3 drugs is omitted if counts are low, or after initial response to improve tolerability, or when the regimen is used as maintenance therapy; When used as maintenance therapy for high risk patients, further delays* 

*Omit day 15 dose if counts are low or when the regimen is used as maintenance therapy; When used as maintenance therapy for high risk patients, lenalidomide dose may be decreased to 10–15 mg per day, and delays can be instituted* 

*good response to improve tolerability; KCd dosing lowered from that used in the initial trial which was conducted in* 

*); Day 8, 9 doses of carfilzomib can be omitted in maintenance phase of therapy after a* 

*All doses need to be adjusted for performance status, renal function, blood counts, and other toxicities.*

Lenalidomide 25 mg oral days 1–21 Dexamethasone per prescribing information

Ixazomib 4 mg oral days 1, 8, 15 Lenalidomide 25 mg oral days 1–21 Dexamethasone 40 mg oral days 1, 8, 15, 22

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**3. Goal of treatment**

Different ranges of regimens have been developed to retard progression of disease using potentially effective in controlling and promising for survival. The

Urgent management of indolent myeloma is not recommended at the present time; rather treatment should be considered in all symptomatic patients with an active myeloma criteria (the CRAB criteria) (hypercalcaemia >11.0 mg/dl), creati-

The overall goal of treatment of MM is to improve survival [14, 15]. A complete response (CR) has been observed only in few patients with conventional chemotherapy regimens. The use of high-dose therapy followed by ASCT and the advent of novel therapies, such as thalidomide, lenalidomide, and bortezomib gained much promises [14, 15], and with such treatment many patients are gaining the much needed improvement and CR. Studies reported that the success of CR correlates with

most commonly used drug combinations are listed in **Table 1**.

nine >2.0 mg/ml, anemia (Hb < 10 mg/dL), active bone lesions), [9].

**2.3 Symptomatic versus asymptomatic myeloma**

*toxicity and similar efficacy compared to intravenous administration.*

*Carfilzomib can also considered in a once a week schedule of 70 mg/m2*

survival, and hence the role of CR as an endpoint in myeloma therapy is becoming prominence. It should also be noted that the benefit of CR is not the same with all treatment regimens [15, 16]. Emerging evidence with novel medications showed that continued treatment has resulted in prolong CR and improved response [16].
