REGIMEN

DOSING

Preferred Regimens

Bortezomib + Cyclophosphamide + Dexamethasone2-55,a

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally once daily

Days 1-4,9-12,17-20: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks for 3-4 cycles.

OR

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1,8,15: Cyclophosphamide 500mg/m2 orally once daily

Days 1,8,15: Dexamethasone 40mg orally once daily.

Repeat cycle every 3 weeks for 3-4 cycles.

OR

Days 1,8,15,22: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally once daily

Days 1-4,9-12,17-20 (Cycles 1-2): Dexamethasone 40mg orally once daily followed by:

Day 1,8,15,22 (Cycles 3 and 4): Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks for 3-4 cycles.

Bortezomib + Lenalidomide + Dexamethasone
(Category 1)2,5-8

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-14: Lenalidomide 25mg orally once daily

Days 1-2,4-5,8-9,11-12: Dexamethasone 20mg orally once daily OR

Days 1,8,15: Dexamethasone 40mg orally once daily.

Repeat cycle every 3 weeks for 3-4 cycles.

Other Recommended Regimens

Carfilzomib + Lenalidomide + Dexamethasone6,9-11,b,c

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 10-30 minutes daily, followed by:

Days 8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 10-30 minutes

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally or IV daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1-2;8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 10-30 minutes daily

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,15,22 (Cycles 2-4): Dexamethasone 40mg orally or IV daily followed by:

Days 1,8,15,22 (Cycles 5-8): Dexamethasone 20mg orally or IV daily.

Repeat cycle every 4 weeks for 7 cycles beginning with Cycle 2.

OR

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 10-30 minutes daily, followed by:

Days 8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 10-30 minutes daily

Days 1-2: Lenalidomide 25mg orally once daily

Days 1-2;8-9;15-16;22-23: Dexamethasone 20mg orally or IV once daily,

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1-2;8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 10-30 minutes daily.

Days 1-21: Lenalidomide 25mg orally once daily

Days 1-2;8-9;15-16;22-23 (Cycles 2-4): Dexamethasone 20mg orally or IV once daily, followed by:

Days 1-2;8-9;15-16;22-23 (Cycles 5-8): Dexamethasone 10mg orally or IV once daily.

Repeat cycle every 4 weeks for 7 cycles beginning with cycle 7.

Daratumumab + Lenalidomide + Bortezomib + Dexamethasone2,6,12,13,d

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-14: Lenalidomide 25mg orally once daily

Days 1-2;8-9;15-16: Dexamethasone 20mg orally once daily

Days 1,8,15: Daratumumab 16mg/kg IV.

Repeat cycle every 3 weeks for 4 cycles (Cycles 1-4), followed by:

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-14: Lenalidomide 25mg orally once daily

Days 1-2;8-9;15-16: Dexamethasone 20mg orally once daily

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 3 weeks for 2 cycles (Cycles 5-6), followed by maintenance therapy with:

Days 1-21 (Cycles 7-9): Lenalidomide 10mg orally once daily, followed by:

Days 1-21 (Cycle 10): Lenalidomide 15mg orally once daily

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks beginning with cycle 7, OR

maintenance therapy with:

Day 1: Daratumumab 16mg/kg IV, with:

Days 1-21 (Cycles 7-9): Lenalidomide 10mg orally once daily, followed by:

Days 1-21 (Cycle 10 and beyond): Lenalidomide 15mg orally once daily.

Repeat cycle every 4 weeks (beginning with Cycle 7).

Ixazomib + Lenalidomide + Dexamethasone
(Category 2B)6,14-16

Days 1,8,15: Ixazomib 4mg orally once daily

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks for 3-4 cycles.

Useful in Certain Circumstances

Bortezomib + Doxorubicin + Dexamethasone2,17,18

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-4: Doxorubicin 9mg/m2 IV push OR Days 1-4: Doxorubicin 9mg/m2continuous infusion over 24 hours

Days 1-4,8-11,15-18: Dexamethasone 40mg orally once daily (Cycle 1), followed by:

Days 1-4: Dexamethasone 40mg orally once daily (beginning with Cycle 2).

Repeat cycle every 3 weeks for 3-4 cycles.

OR

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-4: Doxorubicin 9mg/m2 IV push OR Days 1-4: Doxorubicin 9mg/m2 IV continuous infusion over 24 hours

Days 1-4,9-12,17-20: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks for 3-4 cycles.

Bortezomib + Thalidomide + Dexamethasone
(Category 1)2,19-23

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-21: Thalidomide 50-200mg (usual dose range) orally once daily at bedtime

Days 1-2,4-5,8-9,11-12: Dexamethasone 40mg orally once daily OR Days 1-4,9-12: Dexamethasone 40mg orally once daily.

Repeat cycle every 3 weeks for 3-4 cycles.

Carfilzomib + Cyclophosphamide + Dexamethasone9,24,b,c

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 10 minutes, followed by:

Days 8-9,15-16: Carfilzomib 56mg/m2 (max 123.2mg) IV over 30 minutes

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally or IV once daily.

Administer for one 4-week cycle, followed by:

Days 1-2,8-9,15-16: Carfilzomib 56mg/m2 (max 123.2mg) IV over 30 minutes daily

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks for 7 cycles (Cycles 2-8), followed by maintenance therapy with:

Days 1-2,15-16: Carfilzomib 56mg/m2 (max 123.2mg) IV over 30 minutes.

Repeat cycle every 4 weeks (beginning with Cycle 9).

Cyclophosphamide + Lenalidomide + Dexamethasone2,6,24,25

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks until decision to pursue HCT.

Daratumumab + Bortezomib + Thalidomide + Dexamethasone2,12,19,25,d

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-28: Thalidomide 100mg orally once daily

Days 1-2,8-9,15-16,22-23: Dexamethasone 40mg orally or IV daily

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 2 cycles (Cycles 1-2, induction pre-transplant), followed by:

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-28: Thalidomide 100mg orally once daily

Days 1-2: Dexamethasone 40mg orally or IV daily, followed by:

Days 8-9,15-16: Dexamethasone 20mg orally or IV daily

Days 1,15: 16mg/kg IV.

Repeat cycle every 4 weeks for 2 cycles (Cycles 3-4, induction, pre-transplant), followed by:

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-28: Thalidomide 100mg orally once daily

Days 1-2,8-9,15-16: Dexamethasone 20mg orally or IV daily

Days 1,15: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 2 cycles (Cycles 5-6, consolidation, post-transplant).

Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone2,12,28,d

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1-2: Dexamethasone 20mg IV daily, followed by:

Days 8,15,22: Dexamethasone 40mg IV daily

Days 1-2: Daratumumab 8mg/kg IV daily, followed by:

Days 8,15,22: Daratumumab 16mg/kg IV daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1,8,15,22: Dexamethasone 40mg IV or orally daily

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Administer for one 4-week cycle (Cycle 2), followed by:

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1,8,15,22: Dexamethasone 40 mg IV or orally daily

Days 1,15: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 4 cycles (Cycles 3-6), followed by:

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1,8,15,22: Dexamethasone 40mg IV or orally daily

Day 1: Daratumumab 16mg/kg.

Repeat cycle every 4 weeks for 2 cycles (Cycles 7-8), followed by maintenance therapy (beginning approximately 90 days post-transplant) with:

Day 1: Dexamethasone 12mg IV or orally daily

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for a maximum of 12 cycles.

Dexamethasone + Thalidomide + Cisplatin + Doxorubicin + Cyclophosphamide + Etoposide + Bortezomib (VTD-PACE)2,19,29-31,f,g

Days 1,4,8,11: Bortezomib 1mg/m2 subcutaneous

Days 1-4: Thalidomide 100-200mg orally once daily at bedtime, followed by:

Day 5 and beyond: Thalidomide 50-100mg orally once daily at bedtime

Days 1-4: Dexamethasone 40mg orally once daily

Days 1-4: Cisplatin 10mg/m2 IV continuous infusion over 24 hours daily

Days 1-4: Doxorubicin 10mg/m2 IV continuous infusion over 24 hours daily

Days 1-4: Cyclophosphamide 400mg/m2 IV continuous infusion over 24 hours daily

Days 1-4: Etoposide 40mg/m2 IV continuous infusion over 24 hours daily.

Repeat cycle every 4- to 6-weeks for 4 cycles.

Ixazomib + Cyclophosphamide + Dexamethasone14,32,333,e

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally once daily

Days 1,8,15: Ixazomib 4mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

Preferred Regimens

Lenalidomide
(Category 1)6,34-36,h

Days 1-28 (Cycles 1-3): Lenalidomide 10mg orally once daily, followed by:

Days 1-28 (Cycle 4 and beyond): Lenalidomide 15mg orally once daily.

Repeat cycle every 4 weeks.

OR

Days 1-21: Lenalidomide 10mg orally once daily.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Bortezomib2,38,39

Day 1: Bortezomib 1.3mg/m2 subcutaneous.

Repeat cycle every 2 weeks for up to 2 years.

OR

Days 1,8,15,22: Bortezomib 1.6mg/m2 subcutaneous.

Repeat cycle every 5 weeks for up to 6 months.

Ixazomib (Category 1)14,40

Days 1,8,15 (Cycles 1-4): Ixazomib 3mg orally once daily.

Repeat cycle every 4 weeks for 4 cycles, followed by:

Days 1,8,15 (Cycle 5 and beyond): Ixazomib 4mg orally once daily.

Repeat cycle every 4 weeks for a maximum of 2 years.

Useful in Certain Circumstances

Bortezomib + Lenalidomide2,6,41

Days 1,8,15,22: Bortezomib 1.3mg/m2 subcutaneous

Days 1-21: Lenalidomide 10mg orally once daily.

Repeat cycle every 4 weeks for 3 years, followed by:

Days 1-28: Lenalidomide 10mg orally once daily.

Repeat cycle every 4 weeks.

▶Primary Therapy for Non-Transplant Candidates1

Preferred Regimens

Bortezomib + Cyclophosphamide + Dexamethasone2-5,a

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally once daily

Days 1-4,9-12,17-20: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

OR

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1,8,15: Cyclophosphamide 500mg/m2 orally once daily

Days 1,8,15: Dexamethasone 40mg orally once daily.

Repeat cycle every 3 weeks.

OR

Days 1,8,15,22: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally once daily

Days 1-4,9-12,17-20 (Cycles 1-2): Dexamethasone 40mg orally once daily followed by:

Day 1,8,15,22 (Cycle 3 and beyond): Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

Bortezomib + Lenalidomide + Dexamethasone
(Category 1)2,5-8

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-14: Lenalidomide 25mg orally once daily

Days 1-2,4-5,8-9,11-12: Dexamethasone 20mg orally once daily OR

Days 1,8,15: Dexamethasone 40mg orally once daily.

Repeat cycle every 3 weeks.

Daratumumab + Lenalidomide + Dexamethasone
(Category 1)6,12,42,43,d

Days 1-21: Lenalidomide 25mg orally once daily

Days 1-2,8-9,15-16,22-23: Dexamethasone (age ≤75 years) 20mg IV or orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 2 cycles (Cycles 1-2), followed by:

Days 1-21: Lenalidomide 25mg orally once daily

Days 1-2,15-16: Dexamethasone (age ≤75 years) 20mg IV or orally once daily OR

Days 8,22: Dexamethasone (age ≤75 years) 40mg orally OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily

Days 1,15: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 4 cycles (Cycles 3-6), followed by:

Days 1-21: Lenalidomide 25mg orally once daily

Days 1-2: Dexamethasone (age ≤75 years) 20mg IV or orally once daily

Days 8,15,22: Dexamethasone (age ≤75 years) 40mg orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily.

Repeat cycle every 4 weeks (Cycle 7 and beyond).

Lenalidomide + Low-Dose Dexamethasone
(Category 1)6,44,45,i

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Carfilzomib + Lenalidomide + Dexamethasone6,9-11,b,c

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 10-30 minutes daily, followed by:

Days 8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 10-30 minutes

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally or IV daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1-2;8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 10-30 minutes daily

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,15,22 (Cycles 2-4): Dexamethasone 40mg orally or IV daily followed by:

Days 1,8,15,22 (Cycles 5-8): Dexamethasone 20mg orally or IV daily.

Repeat cycle every 4 weeks for 7 cycles beginning with Cycle 2.

OR

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 10-30 minutes daily, followed by:

Days 8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 10-30 minutes daily

Days 1-2: Lenalidomide 25mg orally once daily

Days 1-2;8-9;15-16;22-23: Dexamethasone 20mg orally or IV once daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1-2;8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 10-30 minutes daily.

Days 1-21: Lenalidomide 25mg orally once daily

Days 1-2;8-9;15-16;22-23 (Cycles 2-4): Dexamethasone 20mg orally or IV once daily, followed by:

Days 1-2;8-9;15-16;22-23 (Cycles 5-8): Dexamethasone 10mg orally or IV once daily.

Repeat cycle every 4 weeks for 7 cycles beginning with cycle 7.

Daratumumab + Bortezomib + Melphalan + Prednisone
(Category 1)2,12,46,a,d

Days 1,4,8,11,22,25,29,32: Bortezomib 1.3mg/m2 subcutaneous

Days 1-4: Melphalan 9mg/m2 orally once daily

Days 2-4: Prednisone 60mg/m2 orally once daily

Days 1,8,15,22,29,36: Daratumumab 16mg/kg IV.

Administer for one 6-week cycle (Cycle 1), followed by:

Days 1,8,22,29: Bortezomib 1.3mg/m2 subcutaneous

Days 1-4: Melphalan 9mg/m2 orally once daily

Days 2-4: Prednisone 60mg/m2 orally

Days 1,22: Daratumumab 16mg/kg IV.

Repeat cycle every 6 weeks for 8 cycles (Cycles 2-9), followed by:

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks (Cycle 10 and beyond).

Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone2,12,28,a,d

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1-2: Dexamethasone 20mg IV daily, followed by:

Days 8,15,22: Dexamethasone 40mg IV daily

Days 1-2: Daratumumab 8mg/kg IV daily, followed by:

Days 8,15,22: Daratumumab 16mg/kg IV daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1,8,15,22: Dexamethasone 40mg IV or orally daily

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Administer for one 4-week cycle (Cycle 2), followed by:

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1,8,15,22: Dexamethasone 40 mg IV or orally daily

Days 1,15: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 4 cycles (Cycles 3-6, followed by:

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1,8,15,22: Dexamethasone 40mg IV or orally daily

Day 1: Daratumumab 16mg/kg.

Repeat cycle every 4 weeks for 2 cycles (Cycles 7-8), followed by maintenance therapy with:

Day 1: Dexamethasone 12mg IV or orally daily

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for a maximum of 12 cycles.

Ixazomib + Lenalidomide + Dexamethasone6,14-16

Days 1,8,15: Ixazomib 4mg orally once daily

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Bortezomib + Dexamethasone2,39

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-2,4-5,8-9,11-12 (Cycles 1-4): Dexamethasone 20mg orally daily, followed by:

Days 1-2,4-5 (Cycles 5 and beyond): Dexamethasone 20mg orally daily.

Repeat cycle every 3 weeks for a maximum of 12 cycles.

Carfilzomib + Cyclophosphamide + Dexamethasone9,26,a-c,e

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 10 minutes, followed by:

Days 8-9,15-16: Carfilzomib 56mg/m2 (max 123.2mg) IV over 30 minutes

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally or IV once daily.

Administer for one 4-week cycle, followed by:

Days 1-2,8-9,15-16: Carfilzomib 56mg/m2 (max 123.2mg) IV over 30 minutes daily

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks for 7 cycles (Cycles 2-8), followed by maintenance therapy with:

Days 1-2,15-16: Carfilzomib 56mg/m2 (max 123.2mg) IV over 30 minutes.

Repeat cycle every 4 weeks (beginning with Cycle 9).

Cyclophosphamide + Lenalidomide + Dexamethasone6,25,47

Days 1,8,15 (Cycles 1-12 only): Cyclophosphamide 300mg/m2 orally once daily

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

▶Maintenance Therapy for Non-Transplant Candidates1

Preferred Regimens

Lenalidomide
(Category 1)6,34-37

Days 1-28 (Cycles 1-3): Lenalidomide 10mg orally once daily, followed by:

Days 1-28 (Cycle 4 and beyond): Lenalidomide 15mg orally once daily.

Repeat cycle every 4 weeks.

OR

Days 1-21: Lenalidomide 10mg orally once daily.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Bortezomib2,38,39

Day 1: Bortezomib 1.3mg/m2 subcutaneous.

Repeat cycle every 2 weeks for up to 2 years.

OR

Days 1,8,15,22: Bortezomib 1.6mg/m2 subcutaneous.

Repeat cycle every 5 weeks for up to 6 months.

Useful in Certain Circumstances

Bortezomib + Lenalidomide2,6,41

Days 1,8,15,22: Bortezomib 1.3mg/m2 subcutaneous

Days 1-21: Lenalidomide 10mg orally once daily.

Repeat cycle every 4 weeks for 3 years, followed by:

Days 1-28: Lenalidomide 10mg orally once daily.

Repeat cycle every 4 weeks.

▶Therapy for Previously Treated Multiple Myeloma1,j,k

Preferred Regimens

Bortezomib + Lenalidomide + Dexamethasone2,6,48,49

Days 1,4,8,11: Bortezomib 1-1.3mg/m2 subcutaneous

Days 1-14: Lenalidomide 15-25mg orally once daily

Days 1-2,4-5,8-9,11-12: Dexamethasone 40 mg orally once daily (Cycles 1-4), followed by:

Days 1-2,4-5,8-9,11-12: Dexamethasone 20mg orally once daily (Cycles 5-8).

Repeat cycle every 3 weeks for a maximum of 8 cycles, followed by:

Days 1,8: Bortezomib 1-1.3mg/m2 subcutaneous

Days 1-14: Lenalidomide 15mg orally once daily

Days 1-2,8-9: Dexamethasone 10mg orally once daily.

Repeat cycle every 3 weeks (Cycle 9 and beyond).

Carfilzomib + Lenalidomide + Dexamethasone
(Category 1)6,9,50,b,c,l

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 10 minutes, followed by:

Days 8-9;15-16: Carfilzomib 27mg/m2 (max 59.4mg) IV over 10 minutes

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Administer for one 28-day cycle (Cycle 1), followed by:

Days 1-2,8-9,15-16: Carfilzomib 27mg/m2 (max 59.4mg) IV over 10 minutes

Days 1-21: Lenalidomide 25mg orally daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks for 11 cycles (Cycles 2-12), followed by:

Days 1-2,15-16: Carfilzomib 27mg/m2 (max 59.4mg) IV over 10 minutes

Days 1-21: Lenalidomide 25mg orally daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks for 6 cycles (Cycles 13-18), followed by:

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks (Cycles 19 and beyond).

Daratumumab + Bortezomib + Dexamethasone
(Category 1)2,12,51,d,f

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-2,4-5,8-9,11-12: Dexamethasone (age ≤75 years) 20mg IV or orally once daily OR

Days 1,4,8,11: Dexamethasone (age >75 years) 20mg IV or orally once daily

Days 1,8,15: 16mg/kg IV.

Repeat cycle every 3 weeks for 3 cycles (Cycles 1-3), followed by:

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-2,4-5,8-9,11-12: Dexamethasone (age ≤75 years) 20mg IV or orally once daily OR

Days 1,4,8,11: Dexamethasone (age >75 years) 20mg IV or orally once daily.

Repeat cycle every 3 weeks for 5 cycles (Cycles 4-8), followed by:

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks (Cycle 9 and beyond).

Daratumumab + Carfilzomib + Dexamethasone
(Category 1)9,12,52,b-d

Day 1: Carfilzomib 20mg/m2 (max 44mg) IV over 30 minutes, followed by:

Days 8,15: Carfilzomib 70mg/m2 (max 154mg) IV over 30 minutes

Days 1-2,8-9,15-16,22-23: Dexamethasone (age ≤75 years) 20mg IV or orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1,8,15: Carfilzomib 70mg/m2 (max 154mg) IV over 30 minutes

Days 1-2,8-9,15-16,22-23: Dexamethasone (age ≤75 years) 20 mg IV or orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20 mg IV or orally once daily

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Administer for one 4-week cycle (Cycle 2), followed by:

Days 1,8,15: Carfilzomib 70mg/m2 (max 154mg) IV over 30 minutes

Days 1-2,15-16: Dexamethasone (age ≤75 years) 20mg IV or orally once daily

Days 8,22: Dexamethasone (≤75 years) 40mg IV or orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily

Days 1,15: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 4 cycles (Cycles 3-6), followed by:

Days 1,8,15: Carfilzomib 70mg/m2 (max 154mg) IV over 30 minutes

Days 1-2: Dexamethasone (age ≤75 years) 20mg IV or orally once daily

Days 8,15,22: Dexamethasone (age ≤75 years) 40mg IV or orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks (Cycle 7 and beyond).

Daratumumab + Lenalidomide + Dexamethasone
(Category 1)6,12,42,43,d

Days 1-21: Lenalidomide 25mg orally once daily

Days 1-2,8-9,15-16,22-23: Dexamethasone (age ≤75 years) 20mg IV or orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 2 cycles (Cycles 1-2), followed by:

Days 1-21: Lenalidomide 25mg orally once daily

Days 1-2,15-16: Dexamethasone (age ≤75 years) 20mg IV or orally once daily OR

Days 8,22: Dexamethasone (age ≤75 years) 40mg orally OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily

Days 1,15: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 4 cycles (Cycles 3-6), followed by:

Days 1-21: Lenalidomide 25mg orally once daily

Days 1-2: Dexamethasone (age ≤75 years) 20mg IV or orally once daily

Days 8,15,22: Dexamethasone (age ≤75 years) 40mg orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily.

Repeat cycle every 4 weeks (Cycle 7 and beyond).

Isatuximab-irfc + Pomalidomide + Dexamethasone
(Category 1)53-56,m

Days 1-21: Pomalidomide 4mg orally once daily

Days 1,8,15,22: Dexamethasone (age <75 years) 40mg orally once daily or IV OR

Days 1,8,15,22: Dexamethasone (age ≥75 years) 20mg orally once daily or IV

Days 1,8,15,22: Isatuximab-ifrc 10mg/kg IV.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1—21: Pomalidomide 4mg orally once daily

Days 1,8,15,22: Dexamethasone (age <75 years) 40mg orally once daily or IV OR

Days 1,8,15,22: Dexamethasone (age ≥75 years) 20mg orally once daily or IV

Days 1,15: Isatuximab-irfc 10mg/kg IV.

Repeat cycle every 4 weeks (Cycle 2 and beyond).

Ixazomib + Lenalidomide + Dexamethasone
(Category 1)6,14-16,l

Days 1,8,15: Ixazomib 4mg orally once daily

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

Ixazomib + Pomalidomide + Dexamethasone52,54,57,58

Days 1,8,15: Ixazomib 4mg orally once daily

Days 1-21: Pomalidomide 4mg orally once daily

Days 1,8,15,22: Dexamethasone (age ≤75 years) 40 mg orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg orally once daily.

Repeat cycle every 4 weeks.

Pomalidomide + Bortezomib + Dexamethasone
(Category 1)54,59,60

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-14: Pomalidomide 4mg orally once daily

Days 1-2,4-5,8-9,11-12: Dexamethasone (age ≤75 years) 20mg orally once daily OR

Days 1-2,4-5,8-9,11-12: Dexamethasone (age >75 years) 10mg orally once daily.

Repeat cycle every 3 weeks for 8 cycles (Cycles 1-8), followed by:

Days 1,8: Bortezomib 1.3mg/m2 subcutaneous

Days 1-14: Pomalidomide 4mg orally once daily

Days 1-2,8-9: Dexamethasone (age ≤75 years) 20mg orally once daily OR

Days 1-2,8-9: Dexamethasone (age >75 years) 10mg orally once daily.

Repeat cycle every 3 weeks (Cycle 9 and beyond).

Other Recommended Regimens

Belantamab Mafodotin-blmf61,62,o

Day 1: Belantamab Mafodetin-blmf 2.5mg/kg IV over 30 minutes.

Repeat cycle every 3 weeks.

Bendamustine + Bortezomib + Dexamethasone2,63,64

Days 1,4: Bendamustine 70mg/m2 IV over 10-60 minutes

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1,4,8,11: Dexamethasone 20mg orally once daily.

Repeat cycle every 4 weeks for 8 cycles or until disease progression.

Bendamustine + Lenalidomide + Dexamethasone6,65

Days 1-2: Bendamustine 75mg/m2 IV over 10-60 minutes

Days 1-21: Lenalidomide 10mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

Bortezomib + Cyclophosphamide + Dexamethasone2,66,67

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-2,4-5,8-9,11-12: Dexamethasone 40mg orally once daily

Days 1,8,15: Cyclophosphamide 500mg orally once daily.

Repeat cycle every 3 weeks.

OR

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-2,4-5,8-9,11-12: Dexamethasone 20mg orally once daily

Days 1,8,15: Cyclophosphamide 50mg orally once daily.

Days 1-21: Cyclophosphamide 50mg orally once daily.

Repeat cycle every 3 weeks for 8 cycles, followed by:

Days 1,8,15,22: Bortezomib 1.3mg/m2 subcutaneous

Days 1-2,8-9,15-16,22-23: Dexamethasone 20mg orally once daily

Days 1-35: Cyclophosphamide 50mg orally once daily.

Repeat cycle every 5 weeks.

Bortezomib + Liposomal Doxorubicin + Dexamethasone
(Category 1)2,68

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Day 4: Liposomal Doxorubicin 30mg/m2 IV

Days 1-4: Dexamethasone 40mg orally once daily.

Repeat cycle every 3 weeks for 8 cycles, followed by:

Days 1,8,15,22,29: Bortezomib 1.3mg/m2 subcutaneous

Day 1-4: Dexamethasone 40mg orally once daily.

Repeat cycle every 5 weeks.

Carfilzomib + Cyclophosphamide + Dexamethasone9,69,70,b,c

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 10 minutes, followed by:

Days 8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 30 minutes

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Day 1,8,15,22: Dexamethasone 40mg orally once daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1-2;8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 30 minutes

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks for 8 cycles (Cycles 2-9), followed by maintenance therapy with:

Days 1-2;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 30 minutes.

Repeat cycle every 4 weeks.

Carfilzomib (twice weekly) + Dexamethasone
(Category 1)9,71,b,c

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 30 minutes daily, followed by:

Days 8-9;15-16: Carfilzomib 56mg/m2 (max 123.2mg) IV over 30 minutes daily

Days 1-2,8-9,15-16,22-23: Dexamethasone 20mg orally once daily.

Administer for one 4-week cycle, followed by:

Days 1-2,8-9,15-16: Carfilzomib 56mg/m2 IV (max 123.2 mg) IV over 30 minutes daily

Days 1-2;8-9;15-16;22-23: Dexamethasone 20mg orally once daily.

Repeat cycle every 4 weeks.

Cyclophosphamide + Lenalidomide + Dexamethasone6,72

Days 1,8,15,21: Cyclophosphamide 500mg orally once daily

Days 1-21: Lenalidomide 25mg orally once daily

Days 1-4,12-15: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

Daratumumab + Cyclophosphamide + Bortezomib + Dexamethasone2,12,28,d

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1-2: Dexamethasone 20mg IV daily, followed by:

Days 8,15,22: Dexamethasone 40mg IV daily

Days 1-2: Daratumumab 8mg/kg IV daily, followed by:

Days 8,15,22: Daratumumab 16mg/kg IV daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1,8,15,22: Dexamethasone 40mg IV or orally daily

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Administer for one 4-week cycle (Cycle 2), followed by:

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1,8,15,22: Dexamethasone 40 mg IV or orally daily

Days 1,15: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 4 cycles (Cycles 3-6, followed by:

Days 1,8,15: Bortezomib 1.5mg/m2 subcutaneous

Days 1,8,15,22: Cyclophosphamide 300mg/m2 orally daily

Days 1,8,15,22: Dexamethasone 40mg IV or orally daily

Day 1: Daratumumab 16mg/kg.

Repeat cycle every 4 weeks for 2 cycles (Cycles 7-8), followed by maintenance therapy with:

Day 1: Dexamethasone 12mg IV or orally daily

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for a maximum of 12 cycles.

Daratumumab + Pomalidomide + Dexamethasone12,54,73,d

Days 1-21: Pomalidomide 4mg orally once daily

Days 1-2,8-9,15-16,22-23: Dexamethasone (age ≤75 years) 20mg IV or orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 2 cycles (Cycles 1-2), followed by:

Days 1-21: Pomalidomide 4mg orally once daily

Days 1-2,15-16: Dexamethasone (age ≤75 years) 20mg IV or orally once daily

Days 8,22: Dexamethasone (age ≤75 years) 40mg orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily

Days 1,15: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 4 cycles (Cycle 3-6), followed by:

Days 1-21: Pomalidomide 4mg orally once daily

Days 1-2: Dexamethasone (age ≤75 years) 20mg IV or orally once daily

Days 8,15,22: Dexamethasone (age ≤75 years) 40mg orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg IV or orally once daily.

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks (Cycle 7 and beyond).

Elotuzumab + Bortezomib + Dexamethasone2,74,75

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1,8,15: Dexamethasone 8mg orally once daily AND 8mg IV prior to Elotuzumab

Days 4,11: Dexamethasone 20mg orally once daily

Days 1,8,15: Elotuzumab 10mg/kg IV.

Repeat cycle every 3 weeks for 2 cycles (Cycles 1-2), followed by:

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1,11: Dexamethasone 8mg orally once daily AND 8mg IV prior to Elotuzumab

Days 4,8: Dexamethasone 20mg orally once daily

Days 1,11: Elotuzumab 10mg/kg IV.

Repeat cycle every 3 weeks for 6 cycles (Cycles 3-8), followed by:

Days 1,8,15: Bortezomib 1.3mg/m2 subcutaneous

Days 1,15: Dexamethasone 8mg orally once daily AND 8mg IV prior to elotuzumab

Day 8: Dexamethasone 20mg orally once daily

Days 1,15: Elotuzumab 10mg/kg IV.

Repeat cycle every 4 weeks (Cycle 9 and beyond).

Elotuzumab + Lenalidomide + Dexamethasone
(Category 1)6,74,76,77,l

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,8,15,22: Dexamethasone 28mg orally AND 8mg IV prior to Elotuzumab

Days 1,8,15,22: Elotuzumab 10mg/kg IV.

Repeat cycle every 4 weeks for 2 cycles (Cycles 1-2), followed by:

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,15: Dexamethasone 28mg orally once daily AND 8mg IV prior to Elotuzumab

Days 8,22: Dexamethasone 40mg orally once daily

Days 1,15: Elotuzumab 10mg/kg IV.

Repeat cycle every 4 weeks (Cycle 3 and beyond).

Elotuzumab + Pomalidomide + Dexamethasone54,74,78,p

Days 1-21: Pomalidomide 4mg orally once daily

Days 1,8,15,22: Dexamethasone (age ≤75 years) 40mg orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg orally once daily

Days 1,8,15,22: Elotuzumab 10mg/kg IV.

Repeat cycle every 4 weeks for 2 cycles (Cycles 1-2), followed by:

Days 1-21: Pomalidomide 4mg orally once daily

Days 1,8,15,22: Dexamethasone (age ≤75 years) 40mg orally once daily

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg orally once daily

Day 1: Elotuzumab 20mg/kg IV.

Repeat every 4 weeks (Cycle 3 and beyond).

Idecabtagene Vicleucel79,o

See NCCN Multiple Myeloma Guidelines1

Isatuximab-ifrc + Carfilzolmib + Dexamethasone9,53,b,c

See NCCN Multiple Myeloma Guidelines1

Ixazomib + Cyclophosphamide + Dexamethasone14,32,33

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Days 1,8,15: Ixazomib 4mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

Melphalan Flufenamide + Dexamethasone80-83,q

Day 1: Melphalan Flufenamide 40mg IV over 30 minutes

Days 1,8,15,22: Dexamethasone (age <75 years) 40mg orally once daily OR

Days 1,8,15,22: Dexamethasone (age ≥ 75 years) 20mg orally once daily.

Repeat cycle every 4 weeks.

Panobinostat + Bortezomib + Dexamethasone
(Category 1)2,84,85

Day 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1,3,5,8,10,12: Panobinostat 20mg orally once daily

Days 1-2,4-5,8-9,11-12: Dexamethasone 20mg orally once daily.

Repeat cycle every 3 weeks for 8 cycles (Cycles 1-8), followed by:

Days 1,8,22,29: Bortezomib 1.3mg/m2 subcutaneous

Days 1,3,5,8,10,12,22,24,26,29,31,33: Panobinostat 20mg orally once daily

Days 1-2,8-9,22-23,29-30: Dexamethasone 20mg orally once daily.

Repeat cycle every 6 weeks (Cycle 9 and beyond).

Pomalidomiden + Cyclophosphamide + Dexamethasone54,86

Days 1,8,15: Cyclophosphamide 400mg orally once daily

Days 1-21: Pomalidomide 4mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

Pomalidomiden + Carfilzomib + Dexamethasone9,54,87,88,b,c

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 10 minutes, followed by:

Days 8-9,15-16: Carfilzomib 27mg/m2 (max 59.4mg) IV over 10 minutes

Days 1-21: Pomalidomide 4mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg IV or orally once daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1-2,8-9,15-16: Carfilzomib 27mg/m2 IV over 10 minutes

Days 1-21: Pomalidomide 4mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg IV or orally once daily.

Repeat cycle ever 4 weeks for 5 cycles (Cycles 2-6), followed by:

Days 1-2,15-16: Carfilzomib 27mg/m2 IV over 10 minutes

Days 1-21: Pomalidomide 4mg IV or orally once daily

Days 1,15: Dexamethasone 40mg IV or orally once daily.

Repeat cycle every 4 weeks (Cycle 7 and beyond).

Selinexor + Bortezomib + Dexamethasone (once weekly)
(Category 1)2,89,90

Days 1,8,15,22: Bortezomib 1.3mg/m2 subcutaneous

Days 1-2,8-9,15-16,22-23,29-30: Dexamethasone 20mg orally once daily

Days 1,8,15,22,29: Selinexor 100mg orally once daily.

Repeat cycle every 5 weeks.

Useful in Certain Circumstances

Bendamustine91,92

Days 1-2: Bendamustine 80-150mg/m2 IV over 10-60 minutes (based on dose and product selection).

Repeat cycle every 4 weeks.

Bortezomib + Dexamethasone
(Category 1)2,93-95

Days 1,4,8,11: Bortezomib 1.3mg/m2 subcutaneous

Days 1-2,4-5,8-9,11-12: Dexamethasone 20mg orally once daily.

Repeat cycle every 3 weeks.

Carfilzomib + Cyclophosphamide + Thalidomide + Dexamethasone9,19,96,97,b,c

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 30 minutes, followed by:

Days 8-9;15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 30 minutes

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Days 1-28: Thalidomide 100mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1-2,8-9,15-16: Carfilzomib 36mg/m2 (max 79.2mg) IV over 30 minutes

Days 1,8,15: Cyclophosphamide 300mg/m2 orally

Days 1-28: Thalidomide 100mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks (Cycle 2 and beyond).

OR

Day 1: Carfilzomib 20mg/m2 (max 44mg) IV over 30 minutes, followed by:

Days 8,15: Carfilzomib 70mg/m2 (max 154mg) IV over 30 minutes

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Days 1-28: Thalidomide 100mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1,8,15: Carfilzomib 70mg/m2 (max 154mg) IV over 30 minutes

Days 1,8,15: Cyclophosphamide 300mg/m2 orally once daily

Days 1-28: Thalidomide 100mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks (Cycle 2 and beyond).

Carfilzomib (weekly) + Dexamethasone9,98,99,b,c

Day 1: Carfilzomib 20mg/m2 (max 44mg) IV over 30 minutes, followed by:

Days 8,15: Carfilzomib 70mg/m2 (max 154mg) IV over 30 minutes

Days 1,8,15,22: Dexamethasone 40mg IV or orally once daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1,8,15: Carfilzomib 70mg/m2 (max 154mg) IV over 30 minutes

Days 1,8,15,22: Dexamethasone 40mg IV or orally once daily.

Repeat cycle every 4 weeks for 7 cycles (Cycles 2-8), followed by:

Days 1,8,15: Carfilzomib 70mg/m2 (max 154mg) IV over 30 minutes

Days 1,8,15: Dexamethasone 40mg IV or orally once daily.

Repeat cycle every 4 weeks (beginning with Cycle 9).

Daratumumab12,100,f,t

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 2 cycles (Cycles 1 and 2), followed by:

Days 1,15: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 4 cycles (Cycles 3-6), followed by:

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks (Cycle 7 and beyond).

Dexamethasone + Cyclophosphamide + Etoposide + Cisplatin (DCEP)101,102,f,g

Days 1-4: Dexamethasone 40mg orally once daily

Days 1-4: Cyclophosphamide 400mg/m2 IV continuous infusion over 24 hours

Days 1-4: Etoposide 40mg/m2 IV continuous infusion over 24 hours

Days 1-4: Cisplatin 10-15mg/m2 IV continuous infusion over 24 hours.

Repeat cycle every 4 weeks.

Dexamethasone + Thalidomide + Cisplatin + Doxorubicin + Cyclophosphamide + Etoposide (DT-PACE)2,19,103-105,f,g,l

Days 1-4: Dexamethasone 40mg orally once daily

Days 1-28: Thalidomide 50-200mg orally once daily at bedtime

Days 1-4: Cisplatin 10mg/m2 IV continuous infusion over 24 hours

Days 1-4: Doxorubicin 10mg/m2 IV continuous infusion over 24 hours

Days 1-4: Cyclophosphamide 400mg/m2 IV continuous infusion over 24 hours

Days 1-4: Etoposide 40mg/m2 IV continuous infusion over 24 hours.

Repeat cycle every 4 weeks.

Dexamethasone + Thalidomide + Cisplatin + Doxorubicin + Cyclophosphamide + Etoposide + Bortezomib (VTD-PACE)2,19,29,31,f,g

Days 1,4,8,11: Bortezomib 1mg/m2 subcutaneous

Days 1-4: Thalidomide 100-200mg orally once daily at bedtime, followed by:

Day 5 and beyond: Thalidomide 50-100mg orally once daily at bedtime

Days 1-4: Dexamethasone 40mg orally once daily

Days 1-4: Cisplatin 10mg/m2 IV continuous infusion over 24 hours daily

Days 1-4: Doxorubicin 10mg/m2 IV continuous infusion over 24 hours daily

Days 1-4: Cyclophosphamide 400mg/m2 IV continuous infusion over 24 hours daily

Days 1-4: Etoposide 40mg/m2 IV continuous infusion over 24 hours daily.

Repeat cycle every 4- to 6-weeks.

High-Dose Cyclophosphamide106

Days 1-4: Cyclophosphamide 600mg/m2 IV over 60 minutes.

Repeat cycle every 4 weeks for 2 cycles, followed by every 3-month cycle.

Ixazomib + Dexamethasone14,107

Days 1,8,15: Ixazomib 4mg orally once daily

Days 1-2,8-9,15-16: Dexamethasone 20mg orally once daily.

Repeat cycle every 4 weeks.

Lenalidomide + Dexamethasone
(Category 1)6,108, 109,r

Days 1-21: Lenalidomide 25mg orally once daily

Days 1-4,9-12,17-20: Dexamethasone 40mg orally once daily (Cycles 1-4), followed by:

Days 1-4: Dexamethasone 40mg orally once daily (Cycle 5 and beyond).

Repeat cycle every 4 weeks.

Panobinostats + Carfilzomib9,110,b,c

Days 1-2: Carfilzomib 20mg/m2 (max 44mg) IV over 10-30 minutes, followed by:

Days 8-9,15-16: Carfilzomib 45mg/m2 (max 99mg) IV over 10-30 minutes.

Days 1,3,5,15,17,19: Panobinostat 20mg orally once daily.

Administer for one 4-week cycle (Cycle 1), followed by:

Days 1-2,8-9,15-16: Carfilzomib 45mg/m2 (max 99mg) IV over 10-30 minutes

Days 1,3,5,15,17,19: Panobinostat 20mg orally once daily.

Repeat cycle every 4 weeks (Cycle 2 and beyond).

Panobinostats + Lenalidomide + Dexamethasone6,111

Days 1-21: Lenalidomide 25mg orally once daily

Days 1,3,5,15,17,19: Panobinostat 20mg orally once daily

Days 1,8,15: Dexamethasone 40mg orally once daily.

Repeat cycle every 4 weeks.

Pomalidomiden + Dexamethasone
(Category 1)52,112-114,r

Days 1-21: Pomalidomide 4mg orally once daily

Days 1,8,15,22: Dexamethasone (age ≤75 years) 40mg orally once daily OR

Days 1,8,15,22: Dexamethasone (age >75 years) 20mg orally once daily.

Repeat cycle every 4 weeks.

Selinexor + Daratumumab + Dexamethasone87,115

Days 1,8,15,22: Selinexor 100mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily or IV OR

Days 1-2,8-9,15-16,22-23: Dexamethasone 20mg orally once daily or IV

Days 1,8,15,22: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 2 cycles (Cycles 1-2), followed by:

Days 1,8,15,22: Selinexor 100mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily or IV OR

Days 1-2,8-9,15-16,22-23: Dexamethasone 20mg orally once daily or IV

Days 1,15: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks for 4 cycles (Cycles 3-6), followed by:

Days 1,8,15,22: Selinexor 100mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily or IV OR

Days 1-2,8-9,15-16,22-23: Dexamethasone 20mg orally once daily or IV

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks (Cycle 7 and beyond).

Selinexor + Dexamethasone89,116,117,u

Days 1,3,8,10,15,17,22,24: Selinexor 80mg orally once daily

Days 1,3,8,10,15,17,22,24: Dexamethasone 20mg orally once daily.

Repeat cycle every 4 weeks.

Selinexor + Pomalidomide + Dexamethasone89,118

Days 1-21: Pomalidomide 4mg orally once daily

Days 1,8,15,22: Selinexor 60mg orally once daily

Days 1,8,15,22: Dexamethasone 40mg orally once daily or IV OR

Days 1-2,8-9,15-16,22-23: Dexamethasone 20mg orally once daily or IV.

Repeat cycle every 4 weeks.

Venetoclax + Dexamethasone (only for t(11;14) patients)119,120

Days 1-21: Venetoclax 800mg orally once daily

Days 1,8,15: Dexamethasone (age <75 years) 40mg orally once daily OR

Days 1,8,15: Dexamethasone (age ≥75 years) 20mg orally once daily.

Repeat cycle every 3 weeks.

  a Preferred primarily as initial treatment in patients with acute renal insufficiency or those who have no access to bortezomib/lenalidomide/dexamethasone. Consider switching to bortezomib/lenalidomide/dexamethasone after renal function improved.

  b Hydration is recommended pre-and post-administration of carfilzomib.

  c Carfilzomib can potentially cause cardiac and pulmonary toxicity, especially in elderly patients.

  d Includes both daratumumab for intravenous infusion and daratumuab and hyaluronidase-fihj for subcutaneous injection. Daratumumab and hyaluronidase-fihj for subcutaneous injection have different dosing and administration instructions compared to daratumumab for intravenous infusion.

  e Treatment option for patients with renal insufficiency and/or peripheral neuropathy.

  f Hydration is required with supplemental electrolytes pre- and post-administration of Cisplatin.

  g Generally reserved for the treatment of aggressive multiple myeloma.

  h There appears to be an increased risk for secondary cancers, especially with lenalidomide maintenance following transplant. The risks and benefits of maintenance therapy vs. secondary cancers should be discussed with patients.

  i Continuously until progression. Benboubker L, Dimopoulos MA, Dispenzieri A, et al. Lendalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371:906-917.

  j Consideration for appropriate regimen is based on the context of clinical relapse.

  k If a regimen in this section was used as a primary induction therapy and relapse is >6 mo, the same regimen may be repeated.

  l Clinical trials with these regimens primarily included patients who were lenalidomide-naïve or with lenalidomide-sensitive multiple myeloma.

  m Indicated for patients who have received at least two prior therapies, including lenalidomide and a proteasome inhibitor.

  n Indicated for the treatment of patients who have received at least two prior therapies including an immunomodulatory agent and a proteasome inhibitor and who have demonstrated disease progression within 60 days of completion of the last therapy.

  o Indicated for patients who have received at least four prior therapies, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent.

  p Indicated for the treatment of patients who have received at least two prior therapies including an immunomodulatory agent and a proteasome inhibitor.

  q Indicated for those who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody.

  r Consider single-agent lenalidomide or pomalidomide for patients with steroid intolerance.

  s Indicated for the treatment of patients who have received at least two prior therapies, including bortezomib and an immunomodulatory agent.

  t Indicated for the treatment of patients who have received at least three prior therapies, including a proteasome inhibitor and an immunomodulatory agent or who are double refractory to a proteasome inhibitor and an immunomodulatory agent.

  u Indicated for patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.