Difference between revisions of "Smoldering multiple myeloma"
Warner-admin (talk | contribs) m (Text replacement - "https://ashpublications.org/blood/article/112/8/3122/114933/Seven-year-median-time-to-progression-with" to "https://doi.org/10.1182/blood-2008-06-164228") |
m |
||
Line 29: | Line 29: | ||
*'''2022:''' Vaxman & Gertz [https://doi.org/10.1182/blood.2021011670 How I approach smoldering multiple myeloma] | *'''2022:''' Vaxman & Gertz [https://doi.org/10.1182/blood.2021011670 How I approach smoldering multiple myeloma] | ||
=All lines of therapy= | =All lines of therapy= | ||
− | |||
==Lenalidomide monotherapy {{#subobject:bec321|Regimen=1}}== | ==Lenalidomide monotherapy {{#subobject:bec321|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen {{#subobject:45c352|Variant=1}}=== | ===Regimen {{#subobject:45c352|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 48: | Line 46: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Aspirin]] 325 mg PO once per day | *[[Aspirin]] 325 mg PO once per day | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1200/JCO.19.01740 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7145586/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31652094 PubMed] NCT01169337 | # '''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. [https://doi.org/10.1200/JCO.19.01740 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7145586/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31652094 PubMed] NCT01169337 | ||
− | |||
==Lenalidomide & Dexamethasone (Rd) {{#subobject:gac521|Regimen=1}}== | ==Lenalidomide & Dexamethasone (Rd) {{#subobject:gac521|Regimen=1}}== | ||
Rd: '''<u>R</u>'''evlimid (Lenalidomide) & low-dose '''<u>d</u>'''examethasone | Rd: '''<u>R</u>'''evlimid (Lenalidomide) & low-dose '''<u>d</u>'''examethasone | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:456A52|Variant=1}}=== | ===Regimen {{#subobject:456A52|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 78: | Line 74: | ||
|} | |} | ||
''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.'' | ''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.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | *[[Lenalidomide (Revlimid)]] 25 mg PO once per day on days 1 to 21 | ||
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
*[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4, 12 to 15 | *[[Dexamethasone (Decadron)]] 20 mg PO once per day on days 1 to 4, 12 to 15 | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Aspirin]] 100 mg PO once per day | *[[Aspirin]] 100 mg PO once per day | ||
− | |||
'''28-day cycle for 9 cycles''' | '''28-day cycle for 9 cycles''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*[[#Lenalidomide_monotherapy|Lenalidomide]] maintenance | *[[#Lenalidomide_monotherapy|Lenalidomide]] maintenance | ||
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1056/NEJMoa1300439 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23902483 PubMed] NCT00480363 | # '''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. [https://doi.org/10.1056/NEJMoa1300439 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23902483 PubMed] NCT00480363 | ||
Line 96: | Line 92: | ||
#'''EFC15992:''' NCT03941860 | #'''EFC15992:''' NCT03941860 | ||
#'''ITHACA:''' NCT04270409 | #'''ITHACA:''' NCT04270409 | ||
− | |||
==Melphalan & Prednisone (MP) {{#subobject:4d7e74|Regimen=1}}== | ==Melphalan & Prednisone (MP) {{#subobject:4d7e74|Regimen=1}}== | ||
− | |||
MP: '''<u>M</u>'''elphalan & '''<u>P</u>'''rednisone | MP: '''<u>M</u>'''elphalan & '''<u>P</u>'''rednisone | ||
− | |||
''Note: This regimen is of historical significance'' | ''Note: This regimen is of historical significance'' | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #1, Six cycles of therapy {{#subobject:f71nh0|Variant=1}}=== | ===Regimen variant #1, Six cycles of therapy {{#subobject:f71nh0|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 119: | Line 112: | ||
|} | |} | ||
''Note: Patients on the observation arm of this study received this regimen at progression to symptomatic MM'' | ''Note: Patients on the observation arm of this study received this regimen at progression to symptomatic MM'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Melphalan (Alkeran)]] 0.21 mg/kg PO once per day on days 1 to 4 | *[[Melphalan (Alkeran)]] 0.21 mg/kg PO once per day on days 1 to 4 | ||
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 0.5 mg/kg PO once per day on days 1 to 10 | *[[Prednisone (Sterapred)]] 0.5 mg/kg PO once per day on days 1 to 10 | ||
− | |||
'''42-day cycle for six cycles''' | '''42-day cycle for six cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, Indefinite therapy {{#subobject:f79d0f|Variant=1}}=== | ===Regimen variant #2, Indefinite therapy {{#subobject:f79d0f|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 141: | Line 135: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 4 | *[[Melphalan (Alkeran)]] 0.25 mg/kg PO once per day on days 1 to 4 | ||
====Glucocorticoid therapy==== | ====Glucocorticoid therapy==== | ||
*[[Prednisone (Sterapred)]] 2 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''' | '''42-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1111/j.1600-0609.1993.tb00148.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8440364 PubMed] | # 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. [https://doi.org/10.1111/j.1600-0609.1993.tb00148.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8440364 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. [https://doi.org/10.1054/bjoc.1999.1087 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10755397 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. [https://doi.org/10.1054/bjoc.1999.1087 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10755397 PubMed] | ||
− | |||
==Observation== | ==Observation== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen=== | ===Regimen=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 192: | Line 186: | ||
|- | |- | ||
|} | |} | ||
− | |||
''No treatment.'' | ''No treatment.'' | ||
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1111/j.1600-0609.1993.tb00148.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8440364 PubMed] | # 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. [https://doi.org/10.1111/j.1600-0609.1993.tb00148.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8440364 PubMed] | ||
Line 202: | Line 195: | ||
# '''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. [https://doi.org/10.1200/JCO.19.01740 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7145586/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31652094 PubMed] NCT01169337 | # '''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. [https://doi.org/10.1200/JCO.19.01740 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7145586/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31652094 PubMed] NCT01169337 | ||
# '''AQUILA:''' NCT03301220 | # '''AQUILA:''' NCT03301220 | ||
− | |||
==Thalidomide monotherapy {{#subobject:bacb11|Regimen=1}}== | ==Thalidomide monotherapy {{#subobject:bacb11|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
===Regimen variant #1, 200 mg/d, indefinite therapy {{#subobject:fabn70|Variant=1}}=== | ===Regimen variant #1, 200 mg/d, indefinite therapy {{#subobject:fabn70|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
Line 228: | Line 219: | ||
|} | |} | ||
''Note: Zoledronic acid was received in both the control and experimental arms.'' | ''Note: Zoledronic acid was received in both the control and experimental arms.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Thalidomide (Thalomid)]] 200 mg PO once per day | *[[Thalidomide (Thalomid)]] 200 mg PO once per day | ||
− | |||
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Zoledronic acid (Zometa)]] 4 mg IV once every three months | *[[Zoledronic acid (Zometa)]] 4 mg IV once every three months | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 200 -> 600 mg/d, indefinite therapy {{#subobject:atn1d0|Variant=1}}=== | ===Regimen variant #2, 200 -> 600 mg/d, indefinite therapy {{#subobject:atn1d0|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 248: | Line 239: | ||
|} | |} | ||
''Note: The median maximal tolerated dose in this study for patients with smoldering myeloma was 400 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'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Thalidomide (Thalomid)]] as follows: | *[[Thalidomide (Thalomid)]] as follows: | ||
**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 28 | **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 28 | ||
**Cycle 2 onwards: 600 mg PO once per day | **Cycle 2 onwards: 600 mg PO once per day | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 200 -> 800 mg/d, indefinite therapy {{#subobject:fabc10|Variant=1}}=== | ===Regimen variant #3, 200 -> 800 mg/d, indefinite therapy {{#subobject:fabc10|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
Line 266: | Line 258: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Thalidomide (Thalomid)]] as follows: | *[[Thalidomide (Thalomid)]] as follows: | ||
Line 271: | Line 264: | ||
**Cycle 2: 600 mg PO once per day on days 1 to 14, then 800 mg PO once per day on days 15 to 28 | **Cycle 2: 600 mg PO once per day on days 1 to 14, then 800 mg PO once per day on days 15 to 28 | ||
**Cycle 3 onwards: 800 mg PO once per day | **Cycle 3 onwards: 800 mg PO once per day | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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 [https://doi.org/10.1038/sj.leu.2402183 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/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://doi.org/10.1038/sj.leu.2402183 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11480571 PubMed] | ||
Line 279: | Line 271: | ||
# '''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://doi.org/10.1182/blood-2008-06-164228 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18669874 PubMed] NCT00083382 | # '''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://doi.org/10.1182/blood-2008-06-164228 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/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 dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22902362 PubMed] NCT00432458 | ||
− | |||
[[Category:Smoldering multiple myeloma regimens]] | [[Category:Smoldering multiple myeloma regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Plasma cell dyscrasias]] | [[Category:Plasma cell dyscrasias]] |
Revision as of 01:10, 25 January 2023
Page editor | Section editor | ||
---|---|---|---|
Samuel M. Rubinstein, MD University of North Carolina Chapel Hill, NC ![]() |
Andrew J. Cowan, MD University of Washington Seattle, WA ![]() |
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
|
Guidelines
"How I Treat"
- 2022: Vaxman & Gertz How I approach smoldering multiple myeloma
All lines of therapy
Lenalidomide monotherapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lonial et al. 2019 (ECOG E3A06) | 2011-2013 | Phase 3 (E-esc) | Observation | Superior PFS PFS36: 91% vs 66% (HR 0.28, 95% CI 0.12-0.62) |
Targeted therapy
- Lenalidomide (Revlimid) 25 mg PO once per day on days 1 to 21
Supportive therapy
- 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 dosing details in manuscript link to PMC article PubMed NCT01169337
Lenalidomide & Dexamethasone (Rd)
Rd: Revlimid (Lenalidomide) & low-dose dexamethasone
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Mateos et al. 2013 (QUIREDEX) | 2007-2010 | Phase 3 (E-esc) | Observation | Superior OS OS36: 94% vs 80% (HR 0.31, 95% CI 0.10-0.91) |
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
Glucocorticoid therapy
- Dexamethasone (Decadron) 20 mg PO once per day on days 1 to 4, 12 to 15
Supportive therapy
- Aspirin 100 mg PO once per day
28-day cycle for 9 cycles
Subsequent treatment
- Lenalidomide maintenance
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 dosing details in manuscript PubMed NCT00480363
- DETER-SMM: NCT03937635
- EFC15992: NCT03941860
- ITHACA: NCT04270409
Melphalan & Prednisone (MP)
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 3 (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
Glucocorticoid therapy
- 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 3 (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
Glucocorticoid therapy
- 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 dosing details in abstract 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 dosing details in abstract PubMed
Observation
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hjorth et al. 1993 | 1983-1988 | Phase 3 (C) | MP | Did not meet endpoint of OS |
Riccardi et al. 2000 (MM87/MM90) | 1987-1993 | Phase 3 (C) | MP | Did not meet endpoint of OS |
Witzig et al 2012 (MC0289) | 2003-2008 | Phase 3 (C) | Thalidomide | Seems to have inferior TTP |
Mateos et al. 2013 (QUIREDEX) | 2007-2010 | Phase 3 (C) | Rd | Inferior OS |
Lonial et al. 2019 (ECOG E3A06) | 2011-2013 | Phase 3 (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 dosing details in abstract 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 dosing details in abstract 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 dosing details in manuscript 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 dosing details in manuscript 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 dosing details in manuscript link to PMC article PubMed NCT01169337
- AQUILA: NCT03301220
Thalidomide monotherapy
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 2 | ||
Witzig et al. 2012 (MC0289) | 2003-2008 | Phase 3 (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 therapy
- Zoledronic acid (Zometa) 4 mg IV once every three months
Continued indefinitely
Regimen variant #2, 200 -> 600 mg/d, indefinite therapy
Study | Years of enrollment | Evidence |
---|---|---|
Weber et al. 2003 | 1999-2001 | Phase 2 |
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: 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 28
- Cycle 2 onwards: 600 mg PO once per day
28-day cycles
Regimen variant #3, 200 -> 800 mg/d, indefinite therapy
Study | Years of enrollment | Evidence |
---|---|---|
Rajkumar et al. 2001 | NR | Phase 2 |
Targeted therapy
- Thalidomide (Thalomid) as follows:
- 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
- Cycle 2: 600 mg PO once per day on days 1 to 14, then 800 mg PO once per day on days 15 to 28
- Cycle 3 onwards: 800 mg PO once per day
28-day cycles
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 dosing details in abstract 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 dosing details in abstract 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 dosing details in abstract 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 dosing details in manuscript PubMed NCT00432458