Nursing Considerations for Common Therapeutic Agents Used in Multiple Myeloma SELECT REGIMENS DOSING COMMENTS

Agent Considerations Induction Therapy—Transplantation Eligible
n Acyclovir or valacyclovir for HSV prophylaxis is recommended Bortezomib/dexamethasone (VD/Vd)[9] n Bortezomib 1.3 mg/m2 IV* n Some patients
n Adjust dosing for hepatic insufficiency per package insert on Days 1, 4, 8, 11 experience diarrhea,
n Weekly bortezomib (IV) appears less toxic in terms of neuropathy yet may be as effective n Dexamethasone 20/40 mg while others complain
n SQ administration appears less toxic in terms of neuropathy yet may be as effective of constipation
PO on Days 1-4, 9-12 (cycles

Bortezomib[1]
n Techniques to improve SQ administration:
• Adjust needle size to ensure that it corresponds to amount of subcutaneous fat 1-2); Days 1-4 (cycles 3-4) n No dose reductions

Guidance on • Consider using a 90° angle for needles 4-6 mm and a 45° angle for needles ≥ 8 mm to ensure that n Repeat cycle q21d x 4 cycles are necessary for
medication is administered in subcutaneous tissue and not muscle *Note: Bortezomib can be given SC for all
renal insufficiency;
• Use air sandwich technique for creating pockets of air in the needle and syringe before and after regimens however, should be
the drug to prevent seeding of irritating medication into the injection tract given after dialysis

Dosing and
• Offer the IV formulation (1 mg/mL instead of 2.5 mg/mL) split between 2 SQ injections on dialysis days if
• Use topical hydrocortisone cream renal failure
• Administer once it reaches room temperature
n Patients with history of CHF or cardiac disease must be watched closely Bortezomib/cyclophosphamide/ n Bortezomib 1.3 mg/m2 IV* n Same as VD/Vd

Administration
n Start CFZ at 20 mg/m2 for C1 and escalate as tolerated dexamethasone (CyBorD)[10,11] on Days 1, 4, 8, 11 except more
n TLS is rare, but patients with high tumor burden should be screened n Cyclophosphamide 300 mg/ myelosuppression

Carfilzomib[2]
n Those at risk should receive allopurinol 100-300 mg PO on Days 1-21 m2 PO on Days 1, 8, 15, 22 can occur with the
n Consider VTE prophylaxis using risk stratification addition of
n Dexamethasone 40 mg PO

of Therapy
n All patients on carfilzomib should receive HSV prophylaxis (acyclovir, valacyclovir) cyclophosphamide
n Nausea, vomiting can occur; therefore, premedication with 5HT3 receptor antagonist is recommended on Days 1-4, 9-12, 17-20 on
n CFZ can be given after dialysis on dialysis days, but caution should be exercised in renal impairment; a 28-day cycle x 4 cycles,
oral hydration should be encouraged followed by HCT
n Edema is fairly common; diuretics can be used to manage as well as compression stockings and ambulation

for Multiple
Bortezomib/doxorubicin/ n Bortezomib 1.3 mg/m2 IV n Same as VD/Vd
n Low doses of cyclophosphamide are generally well tolerated
dexamethasone[12] on Days 1, 4, 8, 11 except watch for
phosphamide[3]
n Cyclophosphamide can be given orally at a dose of 50 mg PO daily or on a weekly dosing schedule
The higher the cyclophosphamide dose, the higher the risk of myelosuppression. For patients with n Dexamethasone 40 mg PO cardiotoxicity with
Cyclo-

n
cytopenias due to disease or treatment, CBC diff should be obtained weekly on Days 1-4 cumulative doses of

Myeloma
n Educate patients on the risk of infection and exercise precautions (hand washing, avoid people with colds) n Doxorubicin 9 mg/m2 on doxorubicin
Days 1-4

n Screen patients for mood disorders and diabetes before steroids are initiated. Common adverse events Bortezomib/lenalidomide/ n Lenalidomide 25 mg PO n Same as VD/Vd
Dexamethasone,

include hyperglycemia, insomnia, mood swings, flushing, sweating, increased risk of infection dexamethasone (VRD/VRd)[13] on Days 1-14 except watch for
Prednisone[4]

n Patients should not stop steroids abruptly n Bortezomib 1.3 mg/m2 IVP myelosuppression
n Dose reductions are encouraged if steroids negatively affect quality of life on Days 1, 4, 8, 11 with CBC weekly x
n Dexamethasone 20 mg 8 wks
PO on Days 1, 2, 4, 5, 8, 9, n Patients at high risk
Curious which regimens 5 expert 11, 12 for VTE should
Available only through REMS program receive LMWH or
oncologists would choose for
n
n Repeat cycle q21d
n Teratogenic; women should avoid pregnancy warfarin (see
Lenalidomide[5]

specific patient situations? n
n
Alert patient to increased risk of VTE and strategies to minimize
Patients should take ASA 81-325 mg/day and be risk-stratified to determine if therapeutic anticoagulation
checklist)
is warranted per IMWG guidelines Bortezomib/thalidomide/ n Bortezomib 1.3 mg/m2 bolus n Same as VD except
n Adjust dose as necessary for renal function dexamethasone (BTD/BTd)[14] IV on Days 1, 4, 8, 11 (3 no dose reductions
Visit clinicaloptions.com/ n Rash can occur; typically responds to nonsedating antihistamines (loratadine, cetirizine) or diphenhydramine
courses, 21 days each) are required for
Diarrhea with long-term use can be managed with loperamide, diphenoxylate-atropine, and dietary
decisionsupporttools
n
modifications n Thalidomide 100 mg/day on thalidomide
Days 1-14; 200 mg/day on n Start bowel regimen
n Melphalan should be administered on an empty stomach due to variable absorption with food
Melphalan[6]

n Dose-reduce melphalan based on creatinine clearance
Days 15-63 (if tolerated) as increased risk of
n Administer antacids to decrease dyspepsia n Dexamethasone 40 mg/day constipation exists
n Promptly report signs of infection on Days 1, 2, 4, 5, 8, 9, 11,
12 (3 cycles, 21 days each)
n Available only through REMS program
Lenalidomide/dexamethasone (Rd)[15] n Lenalidomide 25 mg PO on Days 1-21
n Teratogenic; women should avoid pregnancy
Pomalidomide[7]

n Patients should take ASA 81-325 mg/day and be risk-stratified to determine if therapeutic n Dexamethasone 40 mg PO on Days 1, 8, 15, 22
anticoagulation is warranted per IMWG guidelines n Repeat cycle q28d
n Alert patient to increased risk of VTE and strategies to minimize
n Fatigue and myelosuppression are major adverse events Cyclophosphamide/lenalidomide/ n Lenalidomide 25 mg PO on Days 1-21 q28d cycle
n Use caution in renal insufficiency, although patients were allowed to participate in clinical trials with dexamethasone[16] n Dexamethasone 40 mg on Days 1, 8, 15, 22 q28d
creatinine ≤ 3.0
n Cyclophosphamide 300 mg/m2 PO on Days 1, 8, 15 of
n Rash can occur; typically responds to nonsedating antihistamines (loratadine, cetirizine) or diphenhydramine
each cycle
n Available only through REMS program
Teratogenic; women should avoid pregnancy Carfilzomib/lenalidomide/ n Carfilzomib 20-36 mg/m2 IV on Days 1, 2, 8, 9, 15, 16
Thalidomide[8]

n
n Patients should take ASA 81-325 mg/day and be risk-stratified to determine if therapeutic anticoagulation dexamethasone[17] q28d. For cycles 8-24 on Days 1, 2, 15, 16.
is warranted per IMWG guidelines n Lenalidomide 25 mg PO on Days 1-21
n Alert patient to increased risk of VTE and strategies to minimize
n Dexamethasone 40/20 mg PO weekly (cycles 1-4/5-8)
n Titration at 50- to 100-mg increments weekly to achieve target dose improves tolerability
n Thalidomide should be dosed at bedtime as it is highly sedating Note: Carfilzomib should be started at 20 mg/m2 IV for the first cycle and
n Use caution with elderly escalated slowly as tolerated

Popat R.115:3416-3417. 22. Bortezomib/dexamethasone (VD/Vd)[18] n Bortezomib 1. n Repeat cycle q21d within 48 hrs of dosing) 21.11:831-840.366: n Risk for cardiotoxicity increases with cumulative 1759-1769. doxorubicin[28] n PLD 30 mg/m2 IV on Day 4 syndrome (advise against warm baths. San Miguel JF. 9-12. 12 (cycles 1-4). Bringhen S.23:1337-1341.367:825-831. 11. Relapsed/Refractory 13. dose 22. et al. 4. 5. bortezomib on Days 1. et al. and fatigue 35.86:640-645.20] n Prednisone 60 mg/m2 PO on Days 1-4 n Alternatively. (MPR/MPL)[21] n Prednisone 2 mg/kg PO on Days 1-4 wks 9.348: Lenalidomide/dexamethasone n Lenalidomide 25 mg PO on Days 1-21 n Use same dosing and consideration as NDMM 2609-2617. n Use same dosing and consideration as NDMM dexamethasone (VTD/VTd)[29] 8. 2010. 8. 4. 12 40/20 mg PO (cycles 1-4/5-8) as above 16.359: Bortezomib/pegylated liposomal n Bortezomib 1. N Engl J Med. 29. Cavo M.24:431-436. Alkeran [package insert]. 8. Blood. 8. 11 n Alternatively lenalidomide 15 mg/m2 PO on Days 1-14.21:16-19. Lee CK. Deerfield. Summit. et al. lenalidomide (V. GlaxoSmithKline. (RD/Rd)[30. Melphalan/prednisone/lenalidomide n Nine 28-day cycles of melphalan 0. 11. Velcade [package insert].25:3892-3901. et al. 8. Bortezomib/thalidomide/ n Bortezomib 1. 8 and dexamethasone on Days 1. Siegel DS. 8. n Dexamethasone 20 mg/m2 PO on Days 1-4. 2008. IL: Baxter. 15. N Engl J Med. Rajkumar SV. N Engl J Med. VRD/VRd)[25-27] n Dexamethasone 20/40 mg PO on Days 1. NJ: Celgene. VD/Vd.11:29-37. 2008. Br J Haematol. 2006. 2006. 15. Kumar SK. ASH 2012.28: n Lenalidomide 10 mg PO on Days 1-21 4621-4629. 2010. Melphalan/prednisone/bortezomib n Melphalan 9 mg/m2 PO on Days 1-4 n Repeat cycles q42d x 9 cycles n Myelosuppression may be prolonged 6. Thalidomide/dexamethasone[35. n Dexamethasone 40 mg PO on Days 1. Pineda-Roman M. n Bortezomib 1.357: n Etoposide 40 mg/m2/day CIV on Days 1-4 etoposide ± bortezomib (DT-PACE. N Engl J Med. 22 q35d x 3 cycles 3. 9-12 (cycles 1-4). 29 (cycles 5-9) 5-wk cycles 2013. et al. Kyprolis [package insert]. et al. n Repeat cycle q28-42d VTD-PACE)[34] n Cisplatin 10 mg/m2/day CIV on Days 1-4 n Consider VTE prophylaxis using risk stratification 32. 4. et al. Jagannath S. 2003. Blood. 8. Palumbo A. 2012. et al. *Note: Bortezomib can be given SC for all regimens 4. 17-20 5. J Clin Oncol. Harousseau JL. Blood. Days 1.111:3968-3977. et al. 2012. 9. Faiman B. bortezomib 1. 2010. 4. 2. Pomalyst [package insert]. ASCO 2009. et al. 2010. 17-20 (cycles 1-4) n Repeat cycle q28d 26. 15. 2011. Summit. NJ: Celgene. Melphalan/prednisone/thalidomide n Melphalan 4 mg/m2 PO on Days 1-7 n Thalidomide 100 mg PO nightly n Similar to MPR/MPL except less myelosuppressive 10. Leukemia. et al. et al.23] n Prednisone 40 mg/m2 PO on Days 1-7 n Repeat cycle q28d x 6 cycles n Start bowel regimen as increased risk of constipation 11. Bortezomib ± dexamethasone ± n Bortezomib 1. Revlimid [package insert]. Dexamethasone/thalidomide/cisplatin/ n Dexamethasone 40 mg PO on Days 1-4 n Cyclophosphamide 400 mg/m2/day CIV on Days 1-4 n Myelosuppression is possible doxorubicin/cyclophosphamide/ n Thalidomide 200-400 mg PO nightly on Days 1-4 n Must be given in the hospital by continuous infusion 31. South San Francisco. 9. Abstract 3055. 2008. 2009. Orlowski RZ. (or as tolerated) through central venous catheter 2123-2132. 2010.18 mg/kg PO on Days 1-4 n CBC with differential checked weekly x at least 8 2013. n Thalidomide 50-200 mg/day PO qAM beginning in cycle 2 n The study evaluated 8 cycles 24.8:1053-1072. Weber D. ASH 2011. 12. Dimopoulos M. Lancet Oncol. et al. et al. Cambridge. 5. Rajkumar SV. CA: n Dexamethasone 20 mg PO on Days 1. 17-20 constipation. 2013. 22 q28d 14. n Lenalidomide 25 mg PO on Days 1-21 n ASA 81 mg/day for DVT prophylaxis 30. 8.116:4745-4753. Expert Rev Anticancer Ther. immersing hands and feet in warm water.3 mg/m2 on Days 1. et al. thrombosis. ASH 2010.0 mg/m2 IV on Days 1. Anderson KC. n Repeat cycle q21d x 8 cycles followed by maintenance bortezomib on Days 1. 15 29. et al. Abstract 8536.3 mg/m2 IV* on Days 1. (MPT)[22. then 27 mg/m2 for ≤ 12 cycles 27. Weber D. 9 18. et al. Richardson PG. et al. et al. restrictive clothing 20. Carfilzomib/dexamethasone[32] n Carfilzomib 20 mg/m2 IV twice weekly for 3 of 4 wks in cycle 1. 4. 11. n Repeat cycle q28d x 6 cycles n Doxorubicin 10 mg/m2/day CIV on Days 1-4 n Consider LMWH. 11 q21d n Dexamethasone 20 mg PO qAM on Days 1. Lenalidomide/dexamethasone (RD/Rd)[15] n Lenalidomide 25 mg PO on Days 1-21 q28d n Dexamethasone 40 mg PO on Days 1-4. *Note: Bortezomib can be given SC for all regimens 19. 2007. 2012. Lancet. 8. 2. Pomalidomide + dexamethasone[24] n Pomalidomide 4 mg PO on Days 1-21 q28d 2008. this dose of steroids can also be used in relapsed MM 28. 8. et al. 8. 15. 2003. J Clin Oncol. 25. 2008. MA: Millennium. Research Triangle Park.3 mg/m2 IV* on Days 1.3 mg/m2 IV on Days 1. et al. et al. et al. 22. bortezomib 1. 32 (cycles 1-4) and on Days 1. . Niesvizky R. Am J Hematol. 2007. n Repeat cycle q21d x 8 cycles followed by maintenance n Repeat q21d for 8 cycles followed by maintenance 17. Induction Therapy—Transplantation Ineligible 2012.36] n Thalidomide 200-400 mg PO nightly n Adverse events include infection. 8. 2. Richardson PG. 11. n Dexamethasone 4 mg IV prior to carfilzomib for the first cycle Note: Newly diagnosed MM studies use dexamethasone 20 mg PO on carfilzomib days. Jakubowiak AJ. 4. n Repeat cycle q28d 36.91: 929-934. 2003. Reeder CB. J Clin Oncol. Reece DE. N Engl J Med.3 mg/m2 on Days 1. 2. 9-12. Abstract 478. 11 2. Abstract 8543. Abstract 4053.141:512-516.0 mg/m2 IV and dexamethasone 9.21:2732-2739. J Clin Oncol. 25.376:2075-2085. bortezomib on Days 1. 8. 15. et al. NJ: Celgene. ASCO 2013. 22 q35d × 5 cycles lenalidomide on Days 1-14.22: n Prednisone 100 mg q2d in a 28-day cycle lenalidomide[33] 1419-1427. Leukemia. Lancet. et al. Blood. Reeder CB. 4. 4. Richardson PG. 2. Thalomid [package insert]. Palumbo A. Cyclophosphamide/prednisone/ n Cyclophosphamide 300 mg/m2 on Days 1. 4.120:2817-2825. References REGIMEN DOSING COMMENTS 1.31] n Dexamethasone 40 mg PO on Days 1-4. 5 (cycles 5-8) Onyx. Note: Transplantation-eligible patients should NOT receive prolonged doses of melphalan 8. 2007. et al. 2011. 12 beginning in cycle 4 23. 8. Clin J Oncol Nurs. 2013. 5. et al. 34. et al. Haematologica. Cytoxan [package insert]. J Clin Oncol. Palumbo A. 22 with melphalan and prednisone as above x nine 7. 2007. NC: (VMP/MPB)[19. 11 n PLD: Watch for myelosuppression. 2006. 8. especially when hospitalized 33. Summit. hand–foot 906-917.357:2133-2142.

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