Smoldering multiple myeloma
Revision as of 16:22, 7 November 2019 by Samuelrubinstein (talk | contribs) (→MP {{#subobject:4d7e74|Regimen=2}})
| Page editor | Section editor | ||
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Samuel M. Rubinstein, MD Vanderbilt University Nashville, TN  rubinstein_md
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Andrew J. Cowan, MD University of Washington Seattle, WA andrewcowanmd |
4 regimens on this page
7 variants on this page
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All lines of therapy
Lenalidomide monotherapy
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Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Lonial et al. 2019 (ECOG E3A06) | Phase III (E) | Observation | Superior PFS |
Chemotherapy
- 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. 2019 Oct 25:JCO1901740. [Epub ahead of print] link to original article contains verified protocol PubMed
MP
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MP: Melphalan & Prednisone
Note: This regimen is of historical significance
Variant #1: Six cycles of therapy
Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Riccardi et al. 2000 (MM87/MM90) | Phase III (E) | Observation | Seems not superior |
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 cycles for six cycles
Note: Patients on the observation arm of this study received this regimen at progression to symptomatic MM
Variant #2: Indefinite therapy
Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Hjorth et al. 1993 | Phase III (E) | Observation | Seems not superior |
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, continued until progression
References
- Hjorth M, Hellquist L, Holmberg E, Magnusson B, Rödjer S, Westin J. Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I--a randomized study. Myeloma Group of Western Sweden. 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. Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative Group of Study and Treatment of Multiple Myeloma. Br J Cancer. 2000 Apr;82(7):1254-60. [Epub ahead of print] link to original article contains protocol PubMed
Rd
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Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Mateos et al. 2013 (QUIREDEX) | Phase III (E) | 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.
Chemotherapy
- 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
Thalidomide monotherapy
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Variant #1, 200 mg/d, indefinite therapy
Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Witzig et al. 2012 (MC0289) | Phase III (E) | Observation | Seems to have superior TTP |
| Barlogie et al. 2008 | Phase II |
Note: Zoledronic acid was received in both the control and experimental arms.
Chemotherapy
- Thalidomide (Thalomid) 200 mg PO once per day
Supportive medications
- Zoledronic acid (Zometa) 4 mg IV once every three months
Continued indefinitely
Variant #2, 200 -> 600 mg/d, indefinite therapy
Regimen
| Study | Evidence |
|---|---|
| Weber et al. 2003 | Phase II |
Chemotherapy
- 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
Note: The median maximal tolerated dose in this study for patients with smoldering myeloma was 400 mg PO once per day
Continued indefinitely
Variant #3, 200 -> 800 mg/d, indefinite therapy
Regimen
| Study | Evidence |
|---|---|
| Rajkumar et al. 2001 | Phase II |
Chemotherapy
- 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
- 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
- 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
- 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
- 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. doi: 10.1182/blood-2008-06-164228. Epub 2008 Jul 31. link to original article contains protocol PubMed
Observation
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Regimen
| Study | Evidence | Comparator | Comparative Efficacy |
|---|---|---|---|
| Lonial et al. 2019 (ECOG E3A06) | Phase III (C) | Lenalidomide | Inferior PFS |
| Mateos et al. 2013 (QUIREDEX) | Phase III (C) | Rd | Seems to have inferior OS |
| Witzig et al 2012 (MC0289) | Phase III (C) | Thalidomide | Seems to have inferior TTP |
| Riccardi et al. 2000 (MM87/MM90) | Phase III (C) | MP | Seems not superior |
| Hjorth et al. 1993 | Phase III (C) | MP | Seems not superior |
No treatment.
References
- Hjorth M, Hellquist L, Holmberg E, Magnusson B, Rödjer S, Westin J. Initial versus deferred melphalan-prednisone therapy for asymptomatic multiple myeloma stage I--a randomized study. Myeloma Group of Western Sweden. Eur J Haematol. 1993 Feb;50(2):95-102. link to original article contains protocol PubMed
- 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. 2019 Oct 25:JCO1901740. [Epub ahead of print] link to original article PubMed
- 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
- 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. Long-term survival of stage I multiple myeloma given chemotherapy just after diagnosis or at progression of the disease: a multicentre randomized study. Cooperative Group of Study and Treatment of Multiple Myeloma. Br J Cancer. 2000 Apr;82(7):1254-60. [Epub ahead of print] 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