Multiple Myeloma Treatment Regimens

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MULTIPLE MYELOMA TREATMENT REGIMENS

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient's care or treatment. The National Comprehensive Cancer Network makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

General treatment note: Exposure to myelotoxic agents—including alkylating agents and nitrosoureas—should be limited to avoid compromising stem-cell reserve prior to stem-cell harvest in patients who may be candidates for transplant.1

(Revised 3/2017)

© 2017 by Haymarket Media, Inc.

Primary Therapy for Transplant Candidates1

Note: All recommendations are Category 2A unless otherwise indicated.

Preferred Regimens

REGIMEN

DOSING

Bortezomib + Doxorubicin + Dexamethasone (Category 1)2ab

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC, plus

Days 1–4: Doxorubicin 9mg/m2 IV push or continuous IV infusion over 24 hours daily, plus

Days 1–4, 9–12, and 17–20: Dexamethasone 40mg orally daily for cycle 1, followed by dexamethasone on days 1–4 for cycles 2–4.

Repeat cycle every 3 weeks for 3–4 cycles.

OR

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC, plus

Days 1–4: Doxorubicin 9mg/m2 IV push or continuous IV infusion over 24 hours daily, plus

Days 1–4, 9–12, and 17–20: Dexamethasone 40mg orally daily.

Repeat cycle every 4 weeks for 3–4 cycles.

Bortezomib + Lenalidomide + Dexamethasone (RVD) (Category 1)3-6abc

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Days 1–14: Lenalidomide 25mg orally daily, plus

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

OR

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

Repeat cycle every 3 weeks for 3–4 cycles.

Bortezomib + Cyclophosphamide + Dexamethasone (BCD)7-10ab

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

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

Days 1–4, 9–12, and 17–20: Dexamethasone 40mg orally daily.

Repeat cycle every 4 weeks for 3–4 cycles.

OR

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Days 1, 8, and 15: Cyclophosphamide 500mg/m2/day orally

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

Repeat cycle every 3 weeks for 3–4 cycles.

OR

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Day 1: Cyclophosphamide 900mg/m2 IV over 60 minutes

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

Repeat cycle every 3 weeks for 3–4 cycles.

Other Regimens

Bortezomib + Dexamethasone (Category 1)11,12abd

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC, plus

Days 1–4 (all cycles) and 9–12 (cycles 1 and 2): Dexamethasone 40mg orally daily.

OR

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

Repeat cycle every 3 weeks for 3–4 cycles.

Carfilzomib + Lenalidomide + Dexamethasone (CRD)13,14ac

Cycle 1:

Days 1 and 2: Carfilzomib 20mg/m2 IV over 10 minutes

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

Days 1–21: Lenalidomide 25mg orally daily

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

Cycles 2–12:

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

Days 1–21: Lenalidomide 25mg orally daily

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

Repeat cycle every 4 weeks.

Subsequent Cycles:

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

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

Days 1–21: Lenalidomide 25 mg orally daily.

Repeat cycle every 4 weeks through cycle 13, then continue lenalidomide and dexamethasone only thereafter.

Ixazomib + Lenalidomide + Dexamethasone15c

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

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

Days 1–21: Lenalidomide 25mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Lenalidomide + Dexamethasone (Category 1)16-18cd

Days 1–21: Lenalidomide 25mg orally daily, plus

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

OR

Days 1–4, 9–12, and 17–20: Dexamethasone 40mg orally daily.

Repeat cycle every 4 weeks for 3–4 cycles.

OR

Days 1–28: Lenalidomide 25mg orally daily

Days 1–4, 9–12, and 17–20: Dexamethasone 40mg orally daily.

Repeat cycle every 5 weeks for 3–4 cycles.

Bortezomib + Thalidomide + Dexamethasone (Category 1)19-22abc

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Days 1–21: Thalidomide 50–200mg orally daily at bedtime, plus

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

OR

Days 1–4 and 9–12: Dexamethasone 40mg orally daily.

OR

Days 1–4 (all cycles) and 9–12 (cycles 1 and 2): Dexamethasone 40mg orally daily.

Repeat cycle every 3 weeks for 3–4 cycles.

Primary Therapy for Non-Transplant Candidates1

Preferred Regimens

Lenalidomide + Low-dose Dexamethasone (Category 1)23,24cd

Days 1–21: Lenalidomide 25mg orally daily

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

Repeat cycle every 4 weeks until maximal response, disease progression, or unacceptable toxicity.

Bortezomib + Cyclophosphamide + Dexamethasone25ab

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

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

Days 1–4, 9–12, and 17–20: Dexamethasone 40mg orally daily.

Repeat cycle every 4 weeks for 3–4 cycles.

OR

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Days 1, 8, and 15: Cyclophosphamide 500mg/m2/day orally

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

Repeat cycle every 3 weeks for 3–4 cycles.

OR

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Day 1: Cyclophosphamide 900mg/m2 IV over 60 minutes

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

Repeat cycle every 3 weeks for 3–4 cycles.

Bortezomib + Lenalidomide + Dexamethasone (Category 1)26abc

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Days 1–21: Lenalidomide 25mg orally daily, plus

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

OR

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

Repeat cycle every 3 weeks for 3–4 cycles.

Other Regimens

Bortezomib + Dexamethasone27abd

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC, plus

Days 1–4 (all cycles) and 9–12 (cycles 1 and 2): Dexamethasone 40mg orally daily.

OR

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

Repeat cycle every 3 weeks until maximal response, disease progression, or unacceptable toxicity.

Carfilzomib + Lenalidomide + Dexamethasone (Category 2B)13ac

Cycle 1:

Days 1 and 2: Carfilzomib 20mg/m2 IV over 10 minutes

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

Days 1–21: Lenalidomide 25mg orally daily

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

Cycles 2–12:

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

Days 1–21: Lenalidomide 25mg orally daily

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

Repeat cycle every 4 weeks.

Subsequent Cycles:

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

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

Days 1–21: Lenalidomide 25 mg orally daily.

Repeat cycle every 4 weeks through cycle 13, then continue lenalidomide and dexamethasone only thereafter.

Ixazomib + Lenalidomide + Dexamethasone15ac

Days 1, 8, and 15: Ixazomib 4mg orally

Days 1, 8, 15, and 22: Dexamethasone 40mg orally

Days 1–21: Lenalidomide 25mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Maintenance Therapy1

Bortezomib28ab

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC.

Repeat cycle every 2 weeks for 2 years or until disease progression or unacceptable toxicity.

OR

Days 1, 8, 15, and 22: Bortezomib 1.6mg/m2 IV push over 3–5 seconds or SC.

Repeat cycle every 5 weeks for 6 months or until disease progression or unacceptable toxicity.

Lenalidomide (Category 1)29,30c

Days 1–28: Lenalidomide 10mg orally daily for 3 cycles, followed by 15mg for subsequent cycles.

OR

Days 1–21: Lenalidomide 10mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Therapy for Previously Treated Multiple Myeloma1

Preferred Regimens

Repeat induction therapy if relapse > 6 months.

Bortezomib + Dexamethasone (Category 1)31,32abd

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC, plus

Days 1–4 (all cycles) and 9–12 (cycles 1 and 2): Dexamethasone 40mg orally daily.

OR

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

Repeat cycle every 3 weeks for 3–4 cycles.

Bortezomib + Cyclophosphamide + Dexamethasone33,34ab

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Days 1, 8, and 15: Cyclophosphamide 500mg orally daily

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

Repeat cycle every 3 weeks until maximal response, disease progression, or unacceptable toxicity.

OR

Cycles 1–8:

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Days 1–21: Cyclophosphamide 50mg orally daily

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

Repeat cycle every 3 weeks for 8 cycles.

Subsequent Cycles:

Days 1, 8, 15, and 22: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Days 1–35: Cyclophosphamide 50mg orally daily

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

Repeat cycle every 5 weeks until maximal response, disease progression, or unacceptable toxicity.

Bortezomib + Lenalidomide + Dexamethasone35,36abc

Cycles 1–8:

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Days 1–14: Lenalidomide 25mg orally daily, plus

Days 1, 2, 4, 5, 8, 9, 11, and 12: Dexamethasone 40mg orally daily for cycles 1–4, followed by dexamethasone 20mg orally daily for cycles 5–8

OR

Days 1, 8, and 15: Dexamethasone 20–40mg orally daily

Repeat cycle every 3 weeks for 8 cycles.

Subsequent Cycles:

Days 1 and 8: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Days 1–14: Lenalidomide 15mg orally daily

Days 1, 2, 8, and 9: Dexamethasone 40mg orally daily.

Repeat cycle every 3 weeks until maximal response, disease progression, or unacceptable toxicity.

Carfilzomib + Dexamethasone (Category 1)37ad

Cycle 1:

Days 1 and 2: Carfilzomib 20mg/m2 IV over 30 minutes

Days 8, 9, 15, and 16: Carfilzomib 56mg/m2 IV over 30 minutes

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

Subsequent Cycles:

Days 1, 2, 8, 9, 15, and 16: Carfilzomib 56mg/m2 IV over 30 minutes

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

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Carfilzomib + Lenalidomide + Dexamethasone (Category 1)38ac

Cycle 1:

Days 1 and 2: Carfilzomib 20mg/m2 IV over 10 minutes.

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

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

Days 1-21: Lenalidomide 25mg orally daily

Cycles 2–12:

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

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

Days 1-21: Lenalidomide 25mg orally daily

Subsequent Cycles:

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

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

Days 1–21: Lenalidomide 25mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Daratumumab39,40e

Weeks 1–8:Daratumumab 16mg/kg IV once weekly

Weeks 9–24: Daratumumab 16mg/kg IV every 2 weeks

Subsequent Weeks: Daratumumab 16mg/kg IV every 4 weeks until disease progression or unacceptable toxicity.

Daratumumab + Bortezomib + Dexamethasone (Category 1)41ab

Cycles 1–3:

Days 1, 2, 4, 5, 8, 9, 11, and 12: Dexamethasone 20mg IV or orally daily (20mg weekly in patients >75 years old)

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

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

Repeat cycle every 3 weeks.

Cycles 4–8:

Day 1: Daratumumab 16mg/kg IV

Days 1, 2, 4, 5, 8, 9, 11, and 12: Dexamethasone 20mg IV or orally daily (20mg weekly in patients >75 years old)

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

Repeat cycle every 3 weeks.

Subsequent Cycles:

Day 1: Daratumumab 16mg/kg IV.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Daratumumab + Lenalidomide + Dexamethasone (Category 1)42c

Cycles 1 and 2:

Days 1, 8, 15, and 22: Daratumumab 16mg/kg IV + dexamethasone 40mg orally daily (20mg in patients >75 years old)

Days 1–21: Lenalidomide 25mg orally once daily

Repeat cycle every 4 weeks.

Cycles 3–6:

Days 1, 8, 15, and 22: Dexamethasone 40mg orally daily (20mg in patients >75 years old)

Days 1 and 15: Daratumumab 16mg/kg IV

Days 1–21: Lenalidomide 25mg orally once daily

Repeat cycle every 4 weeks.

Subsequent Cycles:

Day 1: Daratumumab 16mg/kg IV

Days 1–21: Lenalidomide 25mg orally once daily

Days 1, 8, 15, and 22: Dexamethasone 40mg orally daily (20mg in patients >75 years old).

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Elotuzumab + Lenalidomide + Dexamethasone (Category 1)43,44cf

Cycles 1 and 2:

Days 1, 8, 15, and 22: Elotuzumab 10mg/kg IV + dexamethasone 28mg orally between 3 and 24 hours before elotuzumab + 8mg IV between 45 and 90 minutes before elotuzumab

Days 1–21: Lenalidomide 25mg orally daily.

Subsequent Cycles:

Days 1 and 15: Elotuzumab 10mg/kg IV + dexamethasone 28mg orally between 3 and 24 hours before elotuzumab + 8mg IV between 45 and 90 minutes before elotuzumab

Days 1–21: Lenalidomide 25mg orally daily

Days 8 and 22: Dexamethasone 40mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Ixazomib + Lenalidomide + Dexamethasone (Category 1)45acg

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

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

Days 1–21: Lenalidomide 25mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Lenalidomide + Dexamethasone (Category 1)46,47cdh

Days 1–21: Lenalidomide 25mg orally daily

Days 1–4 (all cycles), 9–12, and 17–20 (cycles 1–4): Dexamethasone 40mg orally daily.

Repeat cycle every 4 weeks until maximal response, disease progression, or unacceptable toxicity.

Pomalidomide + Dexamethasone (Category 1)48-53dhi

Days 1–21: Pomalidomide 4mg orally daily

Days 1, 8, 15, and 22: Dexamethasone 40mg (age ≤75 years) or 20mg (age >75 years) orally daily.

Repeat cycle every 4 weeks until maximal response, disease progression, or

unacceptable toxicity.

Pomalidomide + Bortezomib + Dexamethasone54-56i

Days 1–21: Pomalidomide 4mg orally daily

Days 1, 8, 15, and 22: Bortezomib 1.3mg/m2 SC or IV + dexamethasone 40mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Pomalidomide + Carfilzomib + Dexamethasone57,58i

Days 1–21: Pomalidomide 4mg orally daily

Days 1, 2, 8, 9, 15, and 16: Carfilzomib 20 or 27mg/m2 IV

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

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Other Regimens

Bendamustine59,60

Days 1 and 2: Bendamustine 80–150mg/m2 IV over 30 minutes.

Repeat cycle every 4 weeks until maximal response, disease progression, or unacceptable toxicity.

Bendamustine + Bortezomib + Dexamethasone61

Days 1 and 4: Bendamustine 70mg/m2 IV

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV + dexamethasone 20mg IV or orally daily.

Repeat cycle every 4 weeks for a maximum of 8 cycles, or until disease progression or unacceptable toxicity.

Bendamustine + Lenalidomide + Dexamethasone62

Days 1 and 2: Bendamustine 75mg/m2 IV over 30 minutes

Days 1–21: Lenalidomide 10mg orally daily

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

Repeat cycle every 4 weeks until maximal response, disease progression, or unacceptable toxicity.

Bortezomib + Liposomal Doxorubicin (Category 1)63

Days 1, 4, 8, and 11: Bortezomib 1.3mg/m2 IV push over 3–5 seconds or SC

Day 4: Pegylated liposomal doxorubicin 30mg/m2 IV over 60 minutes.

Repeat cycle every 3 weeks until maximal response, disease progression, or unacceptable toxicity.

Cyclophosphamide + Lenalidomide + Dexamethasone64

Days 1, 8, 15, and 22: Cyclophosphamide 500mg orally daily

Day 1–21: Lenalidomide 25mg orally daily

Days 1–4 and 12–15: Dexamethasone 40mg orally daily.

Repeat cycle every 4 weeks until maximal response, disease progression, or unacceptable toxicity.

Dexamethasone + Cyclophosphamide + Etoposide + Cisplatin (DCEP)65,66

Days 1–4: Dexamethasone 40mg/m2 orally daily

Days 1–4: Cyclophosphamide 400mg/m2 continuous IV infusion over 24 hours daily + etoposide 40mg/m2 continuous IV infusion over 24 hours daily + cisplatin 10–15mg/m2 continuous IV infusion over 24 hours daily.

Repeat cycle every 4 weeks until maximal response, disease progression, or unacceptable toxicity.

Dexamethasone + Thalidomide + Cisplatin + Doxorubicin + Cyclophosphamide + Etoposide (DT-PACE)67cj

Days 1–4: Dexamethasone 40mg orally daily

Days 1–4: Cyclophosphamide 400mg/m2 continuous IV infusion over 24 hours daily + etoposide 40mg/m2 continuous IV infusion over 24 hours daily + cisplatin 10mg/m2 continuous IV infusion over 24 hours daily + doxorubicin 10mg/m2 continuous IV infusion over 24 hours daily

Day 1–28: Thalidomide 50–200mg orally daily at bedtime.

Repeat cycle every 4 weeks until maximal response, disease progression, or unacceptable toxicity.

Dexamethasone + Thalidomide + Cisplatin + Doxorubicin + Cyclophosphamide + Etoposide + Bortezomib (VTD-PACE)68cj

Induction:

Days 1, 4, 8, and 11: Bortezomib 1mg/m2 IV push over 3–5 seconds or SC

Day 4–7: Thalidomide 50–200mg orally daily at bedtime + dexamethasone 40mg orally daily

Days 4–7: Cyclophosphamide 400mg/m2 continuous IV infusion over 24 hours daily + etoposide 40mg/m2 continuous IV infusion over 24 hours daily + cisplatin 10mg/m2 continuous IV infusion over 24 hours daily + doxorubicin 10mg/m2 continuous IV infusion over 24 hours daily.

Consolidation:

Cycle 1: Beginning 6 weeks–4 months after last transplant:

Days 1, 4, 8, and 11: Bortezomib 1mg/m2 IV push over 3–5 seconds or SC

Day 1–4: Thalidomide 50–200mg orally daily at bedtime + dexamethasone 40mg orally daily

Days 1–4: Cyclophosphamide 300mg/m2 continuous IV infusion over 24 hours daily + etoposide 30mg/m2 continuous IV infusion over 24 hours daily + cisplatin 7.5mg/m2 continuous IV infusion over 24 hours daily + doxorubicin 7.5mg/m2 continuous IV infusion over 24 hours daily.

Cycle 2: Beginning 2–4 months after cycle 1:

Days 1, 4, 8, and 11: Bortezomib 1mg/m2 IV push over 3–5 seconds or SC

Day 1–4: Thalidomide 50–200mg orally daily at bedtime + dexamethasone 40mg orally daily

Days 4–7: Cyclophosphamide 300mg/m2 continuous IV infusion over 24 hours daily + etoposide 30mg/m2 continuous IV infusion over 24 hours daily + cisplatin 7.5mg/m2 continuous IV infusion over 24 hours daily + doxorubicin 7.5mg/m2 continuous IV infusion over 24 hours daily.

Elotuzumab + Bortezomib + Dexamethasone69ab

Cycles 1 and 2:

Days 1, 8, and 15: Elotuzumab 10mg/kg IV + dexamethasone 8mg orally between 3 and 24 hours before elotuzumab + 8mg IV between 45 and 90 minutes before elotuzumab

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

Days 2, 4, 5, 8, 9, 11: Dexamethasone 20mg orally daily.

Repeat cycle every 3 weeks.

Cycles 3-8:

Days 1 and 11: Elotuzumab 10mg/kg IV + dexamethasone 8mg orally between 3 and 24 hours before elotuzumab + 8mg IV between 45 and 90 minutes before elotuzumab

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

Days 2, 4, 5, 9, 12: Dexamethasone 20mg orally daily.

Repeat cycle every 3 weeks.

Cycles 9 and Later:

Days 1 and 15: Elotuzumab 10mg/kg IV + dexamethasone 8mg orally between 3 and 24 hours before elotuzumab + 8mg IV between 45 and 90 minutes before elotuzumab

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

Days 1, 8, and 15: Bortezomib 1.3mg/m2 SC

Days 2, 8, 9, 16: Dexamethasone 20mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

High-dose Cyclophosphamide70

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

Repeat cycle every 4 weeks for 2 cycles, then every 3 months until maximal response, disease progression, or unacceptable toxicity.

Ixazomib + Dexamethasone71,72adg

Days 1, 8, and 15: Ixazomib 5.5mg orally daily

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

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Panobinostat + Bortezomib + Dexamethasone (Category 1)73,74abk

Cycles 1–8:

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

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

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

Repeat cycle every 3 weeks.

Cycles 9-16:

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

Days 1 and 8: Bortezomib 1.3mg/m2 IV

Days 1, 2, 8 and 9: Dexamethasone 20mg orally.

Repeat cycle every 3 weeks.

Panobinostat + Carfilzomib75,76ak

Cycle 1:

Days 1 and 2: Carfilzomib 20mg/m2 IV

Days 1, 3, 5, 15, 17, and 19: Panobinostat 30mg orally daily.

Days 8, 9, 15, and 16: Carfilzomib 45mg/m2 IV.

Subsequent Cycles:

Days 1, 2, 8, 9, 15, and 16: Carfilzomib 45mg/m2 IV

Days 1, 3, 5, 15, 17, and 19: Panobinostat 30mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

Pomalidomide + Cyclophosphamide + Dexamethasone77,78i

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

Days 1, 8, 15, and 22: Dexamethasone 40mg (20mg for patients >75 years old) orally daily

Days 1–21: Pomalidomide 4mg orally daily.

Repeat cycle every 4 weeks until disease progression or unacceptable toxicity.

a Recommend herpes zoster prophylaxis for patients treated with proteasome inhibitors.

b Subcutaneous bortezomib is the preferred method of administration for patients with pre-existing or high-risk peripheral neuropathy.

c Full-dose aspirin recommended with immunomodulator-based therapy. Therapeutic anticoagulation recommended for those at high risk for thrombosis.

d Triplet regimens should be used as the standard therapy for patients with multiple myeloma; however, elderly or frail patients may be treated with doublet regimens.

e Daratumumab monotherapy is indicated for the treatment of patients who have received at least 3 prior therapies, including a proteasome inhibitor and an immunomodulatory agent or who are double refractory to a proteasome inhibitor and immunomodulatory agent.

f Elotuzumab is indicated in combination with lenalidomide and dexamethasone for the treatment of patients who have received 1 to 3 prior therapies.

g Ixazomib is indicated in combination with lenalidomide and dexamethasone for the treatment of patients who have received at least 1 prior therapy.

h Consider single-agent lenalidomide or pomalidomide for steroid-intolerant individuals.

i Indicated for the treatment of patients who have received at least 2 prior therapies including an immunomodulatory agent and a proteasome inhibitor and who have demonstrated disease progression on or within 60 days of completion of the last therapy.

j Generally reserved for the treatment of aggressive multiple myeloma.

k Indicated for the treatment of patients who have received at least 2 prior regimens, including bortezomib and an immunomodulatory agent.

References

1. NCCN Clinical Practice Guidelines in OncologyTM. Multiple Myeloma. v 3.2017. Available at: https://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed March 2, 2017.

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3. Richardson PG, Weller E, Lonial S, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010;116:679–686.

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Hematologic Cancer Drug Monographs

Leukemias, Lymphomas, And Other Hematologic Cancers

ADCETRIS ALKERAN ALKERAN FOR INJECTION
ARRANON ARZERRA BELEODAQ
BENDEKA BEXXAR BICNU
BLEOMYCIN BLINCYTO BOSULIF
BUSULFEX CAMPATH CERUBIDINE
CLADRIBINE CLOLAR CYCLOPHOSPHAMIDE
CYTARABINE CYTOXAN INJECTION DACOGEN
DARZALEX DEPOCYT DOXIL
DOXORUBICIN HCL DOXORUBICIN HCL SOLUTION DTIC-DOME
EMPLICITI ERWINAZE EVOMELA
FARYDAK FLUDARA FOLOTYN
GAZYVA GLEEVEC GLEOSTINE
HYDREA ICLUSIG IDAMYCIN
IDAMYCIN PFS IMBRUVICA INTRON A
INTRON A SOLN ISTODAX JAKAFI
KEYTRUDA KYPROLIS LEUKERAN
MARQIBO MATULANE METHOTREXATE FOR INJECTION
METHOTREXATE INJECTION MITOXANTRONE HCL MUSTARGEN
MYLERAN NINLARO ONCASPAR
ONTAK OPDIVO PAMIDRONATE DISODIUM INJECTION
PENTOSTATIN POMALYST PURINETHOL
PURIXAN REVLIMID RITUXAN
SPRYCEL SYNRIBO TABLOID
TARGRETIN TARGRETIN GEL TASIGNA
THALOMID TREANDA TREXALL
TRISENOX UVADEX VALCHLOR
VELCADE VENCLEXTA VESANOID
VIDAZA VINBLASTINE FOR INJECTION VINBLASTINE INJECTION
VINCASAR PFS VUMON ZEVALIN
ZOLINZA ZOMETA ZYDELIG

Data provided by the Monthly Prescribing Reference (MPR) Hematology/Oncology Edition.