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.

Did this answer your question?

Yes No

Additional feedback? (Optional)

Thank you for your feedback!

Kumar A, Galeb S, Djulbegovic B. Treatment of patients with multiple myeloma: an overview of systematic reviews. Acta Haematol. 2011. 125(1-2):8-22. [Medline].
Nadal E, Giné E, Bladé J, Esteve J, et al. High-dose therapy/autologous stem cell transplantation in patients with chemosensitive multiple myeloma: predictors of complete remission. Bone Marrow Transplant. 2004 Jan. 33(1):61-4. [Medline].
[Guideline] NCCN Clinical Practice Guidelines in Oncology: Multiple Myeloma. V3 2019. Available at http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. 2019 June 19; Accessed: July 1, 2019.
Reeder CB, Reece DE, Kukreti V, Chen C, Trudel S, Hentz J, et al. Cyclophosphamide, bortezomib and dexamethasone induction for newly diagnosed multiple myeloma: high response rates in a phase II clinical trial. Leukemia. 2009 Jul. 23(7):1337-41. [Medline]. [Full Text].
Cavo M, et al; International Myeloma Working Group. International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation. Blood. 2011 Jun 9. 117 (23):6063-73. [Medline]. [Full Text].
Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10. 119(19):4375-82. [Medline]. [Full Text].
Harousseau JL, et al. VELCADE/Dexamethasone (Vel/D) Versus VAD as Induction Treatment Prior to Autologous Stem Cell Transplantation (ASCT) in Newly Diagnosed Multiple Myeloma (MM): Updated Results of the IFM 2005/01 Trial. Blood (ASH Annual Meeting Abstracts) 2007 110: Abstract 450.
Harousseau JL, et al. High Complete and Very Good Partial Response Rates with Bortezomib—Dexamethasone as Induction Prior to ASCT in Newly Diagnosed Patients with High-Risk Myeloma: Results of the IFM2005-01 Phase 3 Trial. Blood (ASH Annual Meeting Abstracts) 2009 114: Abstract 353.
Popat R, Oakervee HE, Hallam S, Curry N, Odeh L, Foot N, et al. Bortezomib, doxorubicin and dexamethasone (PAD) front-line treatment of multiple myeloma: updated results after long-term follow-up. Br J Haematol. 2008 May. 141(4):512-6. [Medline].
Sonneveld P, et al. First analysis of HOVON-65/GMMG-HD4 randomized phase III trial comparing bortezomib, adriamycine, dexamethasone (PAD) vs VAD as induction treatment prior to high dose melphalan (HDM) in patietns with newly diagnosed multiple myeloma. Haematologica 2009; 94[suppl.2]:191 abs. 0473.
Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood. 2010 Aug 5. 116(5):679-86. [Medline]. [Full Text].
Kumar S, Flinn I, Richardson PG, Hari P, Callander N, Noga SJ, et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood. 2012 May 10. 119(19):4375-82. [Medline].
Cavo M, Tacchetti P, Patriarca F, Petrucci MT, Pantani L, Galli M, et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet. 2010 Dec 18. 376(9758):2075-85. [Medline].
Kaufman JL, Nooka A, Vrana M, Gleason C, Heffner LT, Lonial S. Bortezomib, thalidomide, and dexamethasone as induction therapy for patients with symptomatic multiple myeloma: a retrospective study. Cancer. 2010 Jul 1. 116(13):3143-51. [Medline].
Rajkumar SV, Jacobus S, Callander NS, Fonseca R, Vesole DH, Williams ME, et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol. 2010 Jan. 11(1):29-37. [Medline]. [Full Text].
Zonder JA, Crowley J, Hussein MA, Bolejack V, Moore DF Sr, Whittenberger BF, et al. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood. 2010 Dec 23. 116(26):5838-41. [Medline]. [Full Text].
Facon T, Mary JY, Pégourie B, Attal M, Renaud M, Sadoun A, et al. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006 Feb 15. 107(4):1292-8. [Medline].
Rajkumar SV, Hayman SR, Lacy MQ, Dispenzieri A, Geyer SM, Kabat B, et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood. 2005 Dec 15. 106(13):4050-3. [Medline]. [Full Text].
Ludwig H, Hajek R, Tóthová E, Drach J, Adam Z, Labar B, et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood. 2009 Apr 9. 113(15):3435-42. [Medline].
San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008 Aug 28. 359(9):906-17.
Kyle RA, Rajkumar SV. Multiple myeloma. N Engl J Med. 2004 Oct 28. 351(18):1860-73. [Medline].
Hari P, Pasquini MC, Vesole DH. New questions about transplantation in multiple myeloma. Oncology (Williston Park). 2006 Sep. 20(10):1230-42; discussion 1242, 1244, 1249-50. [Medline].
Mateos MV, Hernández JM, Hernández MT, Gutiérrez NC, Palomera L, Fuertes M, et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood. 2006 Oct 1. 108(7):2165-72. [Medline].
Wijermans P, Schaafsma M, Termorshuizen F, Ammerlaan R, Wittebol S, Sinnige H, et al. Phase III study of the value of thalidomide added to melphalan plus prednisone in elderly patients with newly diagnosed multiple myeloma: the HOVON 49 Study. J Clin Oncol. Jul 1, 2010, Epub Jun 1, 2010. 28(19):3160-6. [Medline].
Facon T, Mary JY, Hulin C, Benboubker L, Attal M, Pegourie B, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet. 2007 Oct 6. 370(9594):1209-18. [Medline].
Merchionne F, Perosa F, Dammacco F. New therapies in multiple myeloma. Clin Exp Med. 2007 Sep. 7(3):83-97. [Medline]. [Full Text].
Facon T, Mary JY, Pégourie B, Attal M, Renaud M, Sadoun A, et al. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood. 2006 Feb 15. 107(4):1292-8. [Medline].
Darzalex (daratumumab) [package insert]. Horsham, PA: Janssen Biotech, Inc. June 2019. Available at [Full Text].
Rifkin RM, Gregory SA, Mohrbacher A, Hussein MA. Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: a Phase III multicenter randomized trial. Cancer. 2006 Feb 15. 106(4):848-58. [Medline].
Cavo M, Zamagni E, Tosi P, Tacchetti P, Cellini C, Cangini D, et al. Superiority of thalidomide and dexamethasone over vincristine-doxorubicindexamethasone (VAD) as primary therapy in preparation for autologous transplantation for multiple myeloma. Blood. 2005 Jul 1. 106(1):35-9. [Medline].
Hicks LK, Haynes AE, Reece DE, Walker IR, Herst JA, Meyer RM. A meta-analysis and systematic review of thalidomide for patients with previously untreated multiple myeloma. Cancer Treat Rev. 2008 Aug. 34(5):442-52. [Medline].
Benevolo G, Larocca A, Gentile M, Pregno P, Gay F, Botto B, et al. The efficacy and safety of bortezomib and dexamethasone as a maintenance therapy in patients with advanced multiple myeloma who are responsive to salvage bortezomib-containing regimens. Cancer. 2010 Nov 18. [Medline].
Ghobrial IM, Stewart AK. ASH evidence-based guidelines: what is the role of maintenance therapy in the treatment of multiple myeloma?. Hematology Am Soc Hematol Educ Program. 2009. 587-9. [Medline].
Palumbo A, Gay F, Falco P, Crippa C, Montefusco V, Patriarca F, et al. Bortezomib as induction before autologous transplantation, followed by lenalidomide as consolidation-maintenance in untreated multiple myeloma patients. J Clin Oncol. 2010 Feb 10. 28(5):800-7. [Medline].
Attal M, Harousseau JL, Leyvraz S, Doyen C, Hulin C, Benboubker L, et al. Maintenance therapy with thalidomide improves survival in patients with multiple myeloma. Blood. 2006 Nov 15. 108(10):3289-94. [Medline].
San-Miguel JF, Hungria VT, Yoon SS, Beksac M, Dimopoulos MA, Elghandour A, et al. Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma: a multicentre, randomised, double-blind phase 3 trial. Lancet Oncol. 2014 Oct. 15(11):1195-206. [Medline].
Leleu X, Attal M, Arnulf B, Moreau P, Traulle C, Marit G, et al. Pomalidomide plus low dose dexamethasone is active and well tolerated in bortezomib and lenalidomide refractory multiple myeloma: IFM 2009-02. Blood. 2013 Jan 14. [Medline].
Kyprolis (carfilzomib) [package insert]. South San Francisco, CA: Onyx Pharmaceuticals. July 2012. Available at [Full Text].
Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015 Jan 8. 372 (2):142-52. [Medline]. [Full Text].
Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hájek R, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016 Jan. 17 (1):27-38. [Medline].
Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Oct 6. 375 (14):1319-1331. [Medline]. [Full Text].
Presented at the ASCO Annual Meeting, June 2, 2015. Chicago, IL. Single-agent daratumumab active in heavily pretreated, refractory multiple myeloma (SIRIUS trial). Available at https://am.asco.org/single-agent-daratumumab-active-heavily-pretreated-refractory-multiple-myeloma.
Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med. 2015 Sep 24. 373 (13):1207-19. [Medline].
Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, et al. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Aug 25. 375 (8):754-66. [Medline]. [Full Text].
Moreau P, et al. Ixazomib, an Investigational Oral Proteasome Inhibitor (PI), in Combination with Lenalidomide and Dexamethasone (IRd), Significantly Extends Progression-Free Survival (PFS) for Patients (Pts) with Relapsed and/or Refractory Multiple Myeloma (RRMM): The Phase 3 Tourmaline-MM1 Study (NCT01564537). Presented at the 57th Annual Meeting of the American Society of Hematology. Orlando, FL. Available at https://ash.confex.com/ash/2015/webprogram/Paper79829.html. December 7, 2015;
Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, et al. Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2015 Aug 13. 373 (7):621-31. [Medline].
Dimopoulos MA, Dytfeld D, Grosicki S, Moreau P, Takezako N, Hori M, et al. Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. N Engl J Med. 2018 Nov 8. 379 (19):1811-1822. [Medline].
Ajai C, Vogl DT, et al. Results of the Pivotal STORM Study (Part 2) in Penta-Refractory Multiple Myeloma (MM): Deep and Durable Responses with Oral Selinexor Plus Low Dose Dexamethasone in Patients with Penta-Refractory MM. Blood 2018 132:598. [Full Text].
Xpovio (selinexor) [package insert]. Newton, MA: Karyopharm Therapeutics, Inc. July 2019. Available at [Full Text].
Dimopoulos MA, Terpos E, Chanan-Khan A, Leung N, Ludwig H, Jagannath S, et al. Renal impairment in patients with multiple myeloma: a consensus statement on behalf of the International Myeloma Working Group. J Clin Oncol. 2010 Nov 20. 28(33):4976-84. [Medline].
Palumbo A, Rajkumar SV, Dimopoulos MA, Richardson PG, San Miguel J, Barlogie B, et al. Prevention of thalidomide- and lenalidomide-associated thrombosis in myeloma. Leukemia. 2008 Feb. 22(2):414-23. [Medline].
[Guideline] Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI, et al. Venous Thromboembolism Prophylaxis and Treatment in Patients With Cancer: ASCO Clinical Practice Guideline Update. J Clin Oncol. 2019 Aug 5. JCO1901461. [Medline]. [Full Text].
Kim SJ, Kim K, Do YR, Bae SH, Yang DH, Lee JJ. Low-dose acyclovir is effective for prevention of herpes zoster in myeloma patients treated with bortezomib: a report from the Korean Multiple Myeloma Working Party (KMMWP) Retrospective Study. Jpn J Clin Oncol. 2011 Mar. 41(3):353-7. [Medline].
Terpos E, Roodman GD, Willenbacher W, Shimizu K, Garcia-Sanz R, Durie B, et al. Comparison of denosumab (DMB) with zoledronic acid (ZA) for the treatment of bone disease in patients with newly diagnosed multiple myeloma; an international, randomized, double blind trial (oral presentation S782). Presented at the 22nd Annual Congress of the European Hematology Association, Madrid Spain. 2017 June 25. [Full Text].
Oakervee HE, Popat R, Curry N, Smith P, Morris C, Drake M, et al. PAD combination therapy (PS-341/bortezomib, doxorubicin and dexamethasone) for previously untreated patients with multiple myeloma. Br J Haematol. 2005 Jun. 129(6):755-62. [Medline].

Media Gallery

of 0

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

Answer

Related Questions:

About

Membership

Apps

WebMD Network

Editions

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

Answer

Related Questions:

References

Tables

Contributor Information and Disclosures

Find Us On

About

Membership

Apps

WebMD Network

Editions