Which salvage therapy regimens are used in the treatment of multiple myeloma?

Answer

Salvage therapy regimens

If a sustained remission was obtained with initial therapy, then consideration should be given to using it again. Salvage therapy also includes the regimens listed above that were not previously selected. Triplets yield higher response rate and progression free survival compared with doublets. Frailty and organ function at the time of relapse influence treatment choices. Other regimens are as follows:

Panobinostat 20 mg PO once every other day for three doses/week (on days 1, 3, 5, 8, 10, and 12) of weeks 1 and 2 of each 21-day cycle for eight cycles plus bortezomib and dexamethasone; consider continuing treatment for an additional eight cycles for patients with clinical benefit, unless they have unresolved severe or medically significant toxicity^[35]
Carfilzomib, a proteasome inhibitor, is indicated as monotherapy, in combination with dexamethasone, or in combination with lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma in patients who have received at least 1 prior line of therapy.^{[36, 37, 38]} (See below.)
Pomalidomide is a thalidomide analogue indicated for patients who have received at least two prior therapies (including lenalidomide and bortezomib) and have disease progression on or within 60 days of completion of the last therapy^[39]; pomalidomide dosage is 4 mg PO QD on days 1-21 of repeated 28-day cycles until disease progression; may be given in combination with dexamethasone
Daratumumab is indicated as monotherapy for patients who have received at least 3 prior treatments, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD), or whose disease is refractory to both a PI and an IMiD; dosage is 16 mg/kg IV infusion once weekly (weeks 1-8); reduce frequency to q2wk (weeks 9-24) and ultimately q4wk (week 25 and thereafter) until disease progression; dosing schedule is for combination therapy with lenalidomide or pomalidomide and dexamethasone for patients with relapsed/refractory multiple myeloma and also for monotherapy^{[40, 41, 42, 43]}
Daratumumab is also indicated in combination with bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least 1 prior therapyosage is 16 mg/kg IV infusion once weekly (weeks 19); reduce frequency to q3wk (weeks 10-24) and ultimately q4wk (week 25 and thereafter) until disease progression^{[13, 44, 43]}
Ixazomib (Ninlaro) is a reversible proteasome inhibitor indicated in combination with lenalidomide and dexamethasone for patients with multiple myeloma who have received at least 1 prior therapy; starting dose is 4 mg PO on days 1, 8, and 15 of a 28-day cycle until disease progression^[45] (See below.)
Elotuzumab (Empliciti) is a humanized IgG1 monoclonal antibody targeting SLAMF7 indicated in combination with lenalidomide and dexamethasone for multiple myeloma in patients who have received 1-3 prior therapies; the dose is 10 mg/kg IV weekly for the first two 28-day cycles, and then 10 mg/kg IV q2wk (on days 1 and 15)^[46]
Elotuzumab is also indicated in combination with pomalidomide and dexamethasone for MM in patients who have received 2 or more prior therapies including lenalidomide and a proteasome inhibitor; the dose is 10 mg/kg IV weekly for the first two 28-day cycles, and then 20 mg/kg IV on Day 1 of each cycle starting with cycle 3^[47]

Ixazomib/cyclophosphamide/dexamethasone (treatment option for patients with renal failure and neuropathy) ^[48]:

Ixazomib 4 mg PO on days, 1, 8, and 15 plus cyclophosphamide 400 mg/m ² on days 1, 8, 15, and 22 plus dexamethasone 40 mg PO on days 1, 8, 15, and 22; 28-d cycle for four cycles

Carfilzomib/lenalidomide/dexamethasone (KRD, CRd, preferred in high-risk myeloma) ^[37]:

Carfilzomib on days 1, 2, 8, 9, 15, and 16 during cycles one through 12 (starting dose, 20 mg/m ²10-minute IV infusion on days 1 and 2 of cycle one; target dose, 27 mg/m ²thereafter) and on days 1, 2, 15, and 16 during cycles 13 through 18, after which carfilzomib is discontinued plus lenalidomide 25 mg PO on days 1 through 21 plus dexamethasone 40 mg PO on days 1, 8, 15, and 22; 28-d cycle, repeat until disease progression or unacceptable toxicity
Carfilzomib on days 1, 2, 8, 9, 15, and 16 during cycles one through 12 (starting dose, 20 mg/m ²10-minute IV infusion on days 1 and 2 of cycle one; target dose, 36 mg/m ²thereafter) and on days 1, 2, 15, and 16 in cycles 13 through 18, after which carfilzomib is discontinued plus lenalidomide 25 mg PO on days 1 through 21 plus dexamethasone 20 mg PO on days 1, 2, 8, 9, 15, 16, 22, and 23; 28-d cycle, repeat until disease progression or unacceptable toxicity

Carfilzomib/cyclophosphamide/dexamethasone (treatment option for patients with renal failure and neuropathy)

Carfilzomib 20 mg/m ² on days 1 and 2; if tolerated, escalate to 56 mg/m ² on days 8, 9, 15, and 16 plus cyclophosphamide 300 mg/m ²/day PO on days 1, 8, 15 plus dexamethasone 20 mg PO on days 1, 2, 8, 9, 15, 16, 22, and 23 in cycles one through eight; 28-d cycle, repeat until disease progression or unacceptable toxicity

Penta-refractory regimen

Selinexor is indicated in combination with dexamethasone for adults with relapsed or refractory MM who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.^{[49, 50]} The regimen comprises selinexor 80 mg PO plus dexamethasone 20 mg PO on Days 1 and 3 of each week; continue until disease progression or unacceptable toxicity.

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