Difference between revisions of "Smoldering multiple myeloma"
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# Rajkumar SV, Dispenzieri A, Fonseca R, Lacy MQ, Geyer S, Lust JA, Kyle RA, Greipp PR, Gertz MA, Witzig TE. Thalidomide for previously untreated indolent or smoldering multiple myeloma. Leukemia. 2001 Aug;15(8):1274-6 [https://www.nature.com/articles/2402183 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11480571 PubMed] | # Rajkumar SV, Dispenzieri A, Fonseca R, Lacy MQ, Geyer S, Lust JA, Kyle RA, Greipp PR, Gertz MA, Witzig TE. Thalidomide for previously untreated indolent or smoldering multiple myeloma. Leukemia. 2001 Aug;15(8):1274-6 [https://www.nature.com/articles/2402183 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11480571 PubMed] | ||
# Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol. 2003 Jan 1;21(1):16-9. [https://doi.org/10.1200/jco.2003.03.139 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506164 PubMed] | # Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol. 2003 Jan 1;21(1):16-9. [https://doi.org/10.1200/jco.2003.03.139 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506164 PubMed] | ||
− | # '''UARK 98-036:''' Barlogie B, van Rhee F, Shaughnessy JD Jr, Epstein J, Yaccoby S, Pineda-Roman M, Hollmig K, Alsayed Y, Hoering A, Szymonifka J, Anaissie E, Petty N, Kumar NS, Srivastava G, Jenkins B, Crowley J, Zeldis JB. Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease. Blood. 2008 Oct 15;112(8):3122-5 | + | # '''UARK 98-036:''' Barlogie B, van Rhee F, Shaughnessy JD Jr, Epstein J, Yaccoby S, Pineda-Roman M, Hollmig K, Alsayed Y, Hoering A, Szymonifka J, Anaissie E, Petty N, Kumar NS, Srivastava G, Jenkins B, Crowley J, Zeldis JB. Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease. Blood. 2008 Oct 15;112(8):3122-5. Epub 2008 Jul 31. [https://ashpublications.org/blood/article/112/8/3122/114933/Seven-year-median-time-to-progression-with link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18669874 PubMed] NCT00083382 |
# '''MC0289:''' Witzig TE, Laumann KM, Lacy MQ, Hayman SR, Dispenzieri A, Kumar S, Reeder CB, Roy V, Lust JA, Gertz MA, Greipp PR, Hassoun H, Mandrekar SJ, Rajkumar SV. A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma. Leukemia. 2013 Jan;27(1):220-5. Epub 2012 Aug 20 [https://www.nature.com/articles/leu2012236 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22902362 PubMed] NCT00432458 | # '''MC0289:''' Witzig TE, Laumann KM, Lacy MQ, Hayman SR, Dispenzieri A, Kumar S, Reeder CB, Roy V, Lust JA, Gertz MA, Greipp PR, Hassoun H, Mandrekar SJ, Rajkumar SV. A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma. Leukemia. 2013 Jan;27(1):220-5. Epub 2012 Aug 20 [https://www.nature.com/articles/leu2012236 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22902362 PubMed] NCT00432458 | ||
Revision as of 18:52, 24 April 2021
Page editor | Section editor | ||
---|---|---|---|
Samuel M. Rubinstein, MD University of North Carolina Chapel Hill, NC rubinstein_md |
Andrew J. Cowan, MD University of Washington Seattle, WA andrewcowanmd |
Note: due to its size/complexity, multiple myeloma has been split into sub-pages:
- Induction (transplant eligible and ineligible)
- First-line consolidation and maintenance
- Relapsed/refractory, including subsequent consolidation and maintenance
- Smoldering multiple myeloma [this page]
4 regimens on this page
7 variants on this page
|
All lines of therapy
Lenalidomide monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lonial et al. 2019 (ECOG E3A06) | 2011-2013 | Phase III (E-esc) | Observation | Superior PFS |
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
Supportive medications
- Aspirin 325 mg PO once per day
28-day cycles
References
- ECOG E3A06: Lonial S, Jacobus S, Fonseca R, Weiss M, Kumar S, Orlowski RZ, Kaufman JL, Yacoub AM, Buadi FK, O'Brien T, Matous JV, Anderson DM, Emmons RV, Mahindra A, Wagner LI, Dhodapkar MV, Rajkumar SV. Randomized trial of lenalidomide versus observation in smoldering multiple myeloma. J Clin Oncol. 2020 Apr 10;38(11):1126-1137. Epub 2019 Oct 25. link to original article contains verified protocol link to PMC article PubMed NCT01169337
MP
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MP: Melphalan & Prednisone
Note: This regimen is of historical significance
Regimen variant #1, Six cycles of therapy
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Riccardi et al. 2000 (MM87/MM90) | 1987-1993 | Phase III (E-esc) | Observation | Did not meet endpoint of OS |
Note: Patients on the observation arm of this study received this regimen at progression to symptomatic MM
Chemotherapy
- Melphalan (Alkeran) 0.21 mg/kg PO once per day on days 1 to 4
- Prednisone (Sterapred) 0.5 mg/kg PO once per day on days 1 to 10
42-day cycle for six cycles
Regimen variant #2, Indefinite therapy
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hjorth et al. 1993 | 1983-1988 | Phase III (E-esc) | Observation | Did not meet endpoint of OS |
Chemotherapy
- Melphalan (Alkeran) 0.25 mg/kg PO once per day on days 1 to 4
- Prednisone (Sterapred) 2 mg/kg PO once per day on days 1 to 4
42-day cycles
References
- Hjorth M, Hellquist L, Holmberg E, Magnusson B, Rödjer S, Westin J; Myeloma Group of Western Sweden. Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I--a randomized study. Eur J Haematol. 1993 Feb;50(2):95-102. link to original article contains protocol PubMed
- MM87/MM90: Riccardi A, Mora O, Tinelli C, Valentini D, Brugnatelli S, Spanedda R, De Paoli A, Barbarano L, Di Stasi M, Giordano M, Delfini C, Nicoletti G, Bergonzi C, Rinaldi E, Piccinini L, Ascari E; Cooperative Group of Study and Treatment of Multiple Myeloma. Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Br J Cancer. 2000 Apr;82(7):1254-60. link to original article contains protocol PubMed
Observation
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hjorth et al. 1993 | 1983-1988 | Phase III (C) | MP | Did not meet endpoint of OS |
Riccardi et al. 2000 (MM87/MM90) | 1987-1993 | Phase III (C) | MP | Did not meet endpoint of OS |
Witzig et al 2012 (MC0289) | 2003-2008 | Phase III (C) | Thalidomide | Seems to have inferior TTP |
Mateos et al. 2013 (QUIREDEX) | 2007-2010 | Phase III (C) | Rd | Seems to have inferior OS |
Lonial et al. 2019 (ECOG E3A06) | 2011-2013 | Phase III (C) | Lenalidomide | Inferior PFS |
No treatment.
References
- Hjorth M, Hellquist L, Holmberg E, Magnusson B, Rödjer S, Westin J; Myeloma Group of Western Sweden. Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I--a randomized study. Eur J Haematol. 1993 Feb;50(2):95-102. link to original article contains protocol PubMed
- MM87/MM90: Riccardi A, Mora O, Tinelli C, Valentini D, Brugnatelli S, Spanedda R, De Paoli A, Barbarano L, Di Stasi M, Giordano M, Delfini C, Nicoletti G, Bergonzi C, Rinaldi E, Piccinini L, Ascari E; Cooperative Group of Study and Treatment of Multiple Myeloma. Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Br J Cancer. 2000 Apr;82(7):1254-60. link to original article contains protocol PubMed
- MC0289: Witzig TE, Laumann KM, Lacy MQ, Hayman SR, Dispenzieri A, Kumar S, Reeder CB, Roy V, Lust JA, Gertz MA, Greipp PR, Hassoun H, Mandrekar SJ, Rajkumar SV. A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma. Leukemia. 2013 Jan;27(1):220-5. Epub 2012 Aug 20 link to original article contains verified protocol PubMed NCT00432458
- QUIREDEX: Mateos MV, Hernández MT, Giraldo P, de la Rubia J, de Arriba F, López Corral L, Rosiñol L, Paiva B, Palomera L, Bargay J, Oriol A, Prosper F, López J, Olavarría E, Quintana N, García JL, Bladé J, Lahuerta JJ, San Miguel JF. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013 Aug 1;369(5):438-47. link to original article contains verified protocol PubMed NCT00480363
- ECOG E3A06: Lonial S, Jacobus S, Fonseca R, Weiss M, Kumar S, Orlowski RZ, Kaufman JL, Yacoub AM, Buadi FK, O'Brien T, Matous JV, Anderson DM, Emmons RV, Mahindra A, Wagner LI, Dhodapkar MV, Rajkumar SV. Randomized trial of lenalidomide versus observation in smoldering multiple myeloma. J Clin Oncol. 2020 Apr 10;38(11):1126-1137. Epub 2019 Oct 25. link to original article contains verified protocol link to PMC article PubMed NCT01169337
Lenalidomide & Dexamethasone (Rd)
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mateos et al. 2013 (QUIREDEX) | 2007-2010 | Phase III (E-esc) | Observation | Seems to have superior OS |
Note: QUIREDEX did not require modern imaging modalities (such as MRI) to rule out active myeloma, and therefore it is probable that many patients on this study had active as opposed to smoldering multiple myeloma.
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 12 to 15
Supportive medications
- Aspirin 100 mg PO once per day
28-day cycle for 9 cycles
Subsequent treatment
References
- QUIREDEX: Mateos MV, Hernández MT, Giraldo P, de la Rubia J, de Arriba F, López Corral L, Rosiñol L, Paiva B, Palomera L, Bargay J, Oriol A, Prosper F, López J, Olavarría E, Quintana N, García JL, Bladé J, Lahuerta JJ, San Miguel JF. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. N Engl J Med. 2013 Aug 1;369(5):438-47. link to original article contains verified protocol PubMed NCT00480363
Thalidomide monotherapy
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Regimen variant #1, 200 mg/d, indefinite therapy
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Barlogie et al. 2008 (UARK 98-036) | 1998-NR | Phase II | ||
Witzig et al. 2012 (MC0289) | 2003-2008 | Phase III (E-esc) | Observation | Seems to have superior TTP |
Note: Zoledronic acid was received in both the control and experimental arms.
Targeted therapy
- Thalidomide (Thalomid) 200 mg PO once per day
Supportive medications
- Zoledronic acid (Zometa) 4 mg IV once every three months
Continued indefinitely
Regimen variant #2, 200 -> 600 mg/d, indefinite therapy
Study | Evidence |
---|---|
Weber et al. 2003 | Phase II |
Note: The median maximal tolerated dose in this study for patients with smoldering myeloma was 400 mg PO once per day
Targeted therapy
- Thalidomide (Thalomid) as follows:
- Cycle 1: Cycle 1: 200 mg PO once per day on days 1 to 7, then 300 mg PO once per day on days 8 to 14, then 400 mg PO once per day on days 15 to 21, then 500 mg PO once per day on days 22 to 29
- Cycle 2 onwards: 600 mg PO once per day
Continued indefinitely
Regimen variant #3, 200 -> 800 mg/d, indefinite therapy
Study | Evidence |
---|---|
Rajkumar et al. 2001 | Phase II |
Targeted therapy
- Thalidomide (Thalomid) as follows:
- Cycle 1: Cycle 1: 200 mg PO once per day on days 1 to 14, then 400 mg PO once per day on days 15 to 28, then 600 mg PO once per day on days 29 to 42
- Cycle 2 onwards: 800 mg PO once per day
Continued indefinitely
References
- Rajkumar SV, Dispenzieri A, Fonseca R, Lacy MQ, Geyer S, Lust JA, Kyle RA, Greipp PR, Gertz MA, Witzig TE. Thalidomide for previously untreated indolent or smoldering multiple myeloma. Leukemia. 2001 Aug;15(8):1274-6 link to original article contains protocol PubMed
- Weber D, Rankin K, Gavino M, Delasalle K, Alexanian R. Thalidomide alone or with dexamethasone for previously untreated multiple myeloma. J Clin Oncol. 2003 Jan 1;21(1):16-9. link to original article contains protocol PubMed
- UARK 98-036: Barlogie B, van Rhee F, Shaughnessy JD Jr, Epstein J, Yaccoby S, Pineda-Roman M, Hollmig K, Alsayed Y, Hoering A, Szymonifka J, Anaissie E, Petty N, Kumar NS, Srivastava G, Jenkins B, Crowley J, Zeldis JB. Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease. Blood. 2008 Oct 15;112(8):3122-5. Epub 2008 Jul 31. link to original article contains protocol PubMed NCT00083382
- MC0289: Witzig TE, Laumann KM, Lacy MQ, Hayman SR, Dispenzieri A, Kumar S, Reeder CB, Roy V, Lust JA, Gertz MA, Greipp PR, Hassoun H, Mandrekar SJ, Rajkumar SV. A phase III randomized trial of thalidomide plus zoledronic acid versus zoledronic acid alone in patients with asymptomatic multiple myeloma. Leukemia. 2013 Jan;27(1):220-5. Epub 2012 Aug 20 link to original article contains verified protocol PubMed NCT00432458