Difference between revisions of "Sickle cell anemia"
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− | + | <span id="BackToTop"></span> | |
− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | {{#lst:Editorial board transclusions|heme}} | |
− | + | ''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Sickle cell anemia - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''<br> | |
− | + | *''We have moved [[How I Treat]] articles to a dedicated page.'' | |
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
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{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
=Guidelines= | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
==ASH== | ==ASH== | ||
− | *''' | + | *'''2021:''' Kanter et al. [https://doi.org/10.1182/bloodadvances.2021004394 American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945587/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34581773/ PubMed] |
− | *''' | + | *'''2020:''' Chou et al. [https://doi.org/10.1182/bloodadvances.2019001143 American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988392/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31985807/ PubMed] |
− | + | *'''2020:''' DeBaun et al. [https://doi.org/10.1182/bloodadvances.2019001142 American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7189278/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32298430/ PubMed] | |
− | + | *'''2020:''' Brandow et al. [https://doi.org/10.1182/bloodadvances.2020001851 American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7322963/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32559294/ PubMed] | |
− | *'''2019:''' | + | *'''2019:''' Liem et al. [https://doi.org/10.1182/bloodadvances.2019000916 American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963257/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31794601/ PubMed] |
+ | ==BSH== | ||
+ | *'''2021:''' Oteng-Ntim et al. [https://doi.org/10.1111/bjh.17671 Management of sickle cell disease in pregnancy. A British Society for Haematology Guideline] [https://pubmed.ncbi.nlm.nih.gov/34409598 PubMed] | ||
==NHLBI== | ==NHLBI== | ||
− | *'''2014:''' [https:// | + | *'''2014:''' [https://doi.org/10.1182/bloodadvances.2019000916 Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6963257/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25203083/ PubMed] |
=All lines of therapy= | =All lines of therapy= | ||
==Crizanlizumab monotherapy {{#subobject:76agc4|Regimen=1}}== | ==Crizanlizumab monotherapy {{#subobject:76agc4|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:cbzecd|Variant=1}}=== | ===Regimen {{#subobject:cbzecd|Variant=1}}=== | ||
{| class="wikitable" style="color:white; background-color:#404040" | {| class="wikitable" style="color:white; background-color:#404040" | ||
Line 36: | Line 36: | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 43: | Line 43: | ||
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481200/ Ataga et al. 2016 (SUSTAIN)] | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481200/ Ataga et al. 2016 (SUSTAIN)] | ||
|rowspan=2|2013-2015 | |rowspan=2|2013-2015 | ||
− | |rowspan=2 style="background-color:#1a9851"|Randomized Phase | + | |rowspan=2 style="background-color:#1a9851"|Randomized Phase 2 (E-RT-esc) |
− | |Placebo | + | |1. [[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]] |
− | |style="background-color:#1a9850"|Superior annual rate of crises | + | |style="background-color:#1a9850"|Superior annual rate of crises (primary endpoint) |
|- | |- | ||
− | |[[#Crizanlizumab_monotherapy|Crizanlizumab]]; 2.5 mg/kg | + | |2. [[#Crizanlizumab_monotherapy|Crizanlizumab]]; 2.5 mg/kg |
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
|- | |- | ||
|} | |} | ||
− | ==== | + | <div class="toccolours" style="background-color:#f2f3f4"> |
+ | ====Supportive therapy==== | ||
*[[Crizanlizumab (Adakveo)]] 5 mg/kg IV once on day 1 | *[[Crizanlizumab (Adakveo)]] 5 mg/kg IV once on day 1 | ||
− | |||
'''14-day cycle for 26 cycles (1 year)''' | '''14-day cycle for 26 cycles (1 year)''' | ||
− | + | </div></div> | |
+ | ===References=== | ||
+ | # '''SUSTAIN:''' Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR, Gualandro S, Colella MP, Smith WR, Rollins SA, Stocker JW, Rother RP. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017 Feb 2;376(5):429-439. Epub 2016 Dec 3. [https://doi.org/10.1056/NEJMoa1611770 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481200/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27959701/ PubMed] [https://clinicaltrials.gov/study/NCT01895361 NCT01895361] | ||
+ | ==Exagamglogene autotemcel monotherapy {{#subobject:8dgex1|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:excbt2|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
+ | !style="width: 33%"|Study | ||
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/nejmoa2309676 Frangoul et al. 2024 (CLIMB SCD-121)] | ||
+ | |2018-11-27 to not reported | ||
+ | | style="background-color:#91cf61" |Non-randomized phase 3 (RT) | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#f2f3f4"> | ||
+ | ====Targeted therapy==== | ||
+ | *[[Exagamglogene autotemcel (Casgevy)]] | ||
+ | '''One course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # ''' | + | #'''CLIMB SCD-121:''' Frangoul H, Locatelli F, Sharma A, Bhatia M, Mapara M, Molinari L, Wall D, Liem RI, Telfer P, Shah AJ, Cavazzana M, Corbacioglu S, Rondelli D, Meisel R, Dedeken L, Lobitz S, de Montalembert M, Steinberg MH, Walters MC, Eckrich MJ, Imren S, Bower L, Simard C, Zhou W, Xuan F, Morrow PK, Hobbs WE, Grupp SA; CLIMB SCD-121 Study Group. Exagamglogene Autotemcel for Severe Sickle Cell Disease. N Engl J Med. 2024 May 9;390(18):1649-1662. Epub 2024 Apr 24. [https://doi.org/10.1056/nejmoa2309676 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38661449/ PubMed] [https://clinicaltrials.gov/study/NCT03745287 NCT03745287] |
==Hydroxyurea monotherapy {{#subobject:762af4|Regimen=1}}== | ==Hydroxyurea monotherapy {{#subobject:762af4|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:d87ecd|Variant=1}}=== | ===Regimen {{#subobject:d87ecd|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199505183322001 Charache et al. 1995 (MSH)] |
|1992-1994 | |1992-1994 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |Placebo | + | |[[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]] |
|style="background-color:#1a9850"|Superior annual rate of crises | |style="background-color:#1a9850"|Superior annual rate of crises | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3133619/ Wang et al. 2011 (BABY HUG)] | ||
+ | |2003-2009 | ||
+ | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
+ | |[[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]] | ||
+ | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of splenic and renal function | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#f2f3f4"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Hydroxyurea (Hydrea)]] 15 mg/kg/day PO | *[[Hydroxyurea (Hydrea)]] 15 mg/kg/day PO | ||
− | + | '''Continued indefinitely''' | |
− | ''Doses were subsequently adjusted, see | + | </div> |
− | + | <div class="toccolours" style="background-color:#fff2ae"> | |
+ | ====Dose and schedule modifications==== | ||
+ | ''Doses were subsequently adjusted, see articles for details.'' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''MSH:''' Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med. 1995 May 18;332(20):1317-22. [https:// | + | # '''MSH:''' Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med. 1995 May 18;332(20):1317-22. [https://doi.org/10.1056/NEJM199505183322001 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/7715639/ PubMed] |
− | ## '''Update:''' Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eckman J, Varma M, Ramirez G, Adler B, Smith W, Carlos T, Ataga K, DeCastro L, Bigelow C, Saunthararajah Y, Telfer M, Vichinsky E, Claster S, Shurin S, Bridges K, Waclawiw M, Bonds D, Terrin M. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA. 2003 Apr 2;289(13):1645-51. Erratum in: JAMA. 2003 Aug 13;290(6):756. [ | + | ## '''Update:''' Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eckman J, Varma M, Ramirez G, Adler B, Smith W, Carlos T, Ataga K, DeCastro L, Bigelow C, Saunthararajah Y, Telfer M, Vichinsky E, Claster S, Shurin S, Bridges K, Waclawiw M, Bonds D, Terrin M. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA. 2003 Apr 2;289(13):1645-51. Erratum in: JAMA. 2003 Aug 13;290(6):756. [https://doi.org/10.1001/jama.289.13.1645 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12672732/ PubMed] |
− | ## ''' | + | ## '''HRQoL analysis:''' Ballas SK, Barton FB, Waclawiw MA, Swerdlow P, Eckman JR, Pegelow CH, Koshy M, Barton BA, Bonds DR. Hydroxyurea and sickle cell anemia: effect on quality of life. Health Qual Life Outcomes. 2006 Aug 31;4:59. [https://doi.org/10.1186/1477-7525-4-59 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1569824/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16942629/ PubMed] |
− | #'''NOHARM MTD:''' John CC, Opoka RO, Latham TS, Hume HA, Nabaggala C, Kasirye P, Ndugwa CM, Lane A, Ware RE. Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med. 2020 Jun 25;382(26):2524-2533. [https://doi.org/10.1056/nejmoa2000146 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32579813/ PubMed] | + | #'''BABY HUG:''' Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW; BABY HUG investigators. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011 May 14;377(9778):1663-72. [https://doi.org/10.1016/s0140-6736(11)60355-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3133619/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21571150/ PubMed] [https://clinicaltrials.gov/study/NCT00006400 NCT00006400] |
+ | #'''NOHARM MTD:''' John CC, Opoka RO, Latham TS, Hume HA, Nabaggala C, Kasirye P, Ndugwa CM, Lane A, Ware RE. Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med. 2020 Jun 25;382(26):2524-2533. [https://doi.org/10.1056/nejmoa2000146 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32579813/ PubMed] [https://clinicaltrials.gov/study/NCT03128515 NCT03128515] | ||
==Hydroxyurea & Voxelotor {{#subobject:4eugac|Regimen=1}}== | ==Hydroxyurea & Voxelotor {{#subobject:4eugac|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:f1g718|Variant=1}}=== | ===Regimen {{#subobject:f1g718|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 104: | Line 129: | ||
|- | |- | ||
|rowspan=2|[https://doi.org/10.1056/nejmoa1903212 Vichinsky et al. 2019 (HOPE)] | |rowspan=2|[https://doi.org/10.1056/nejmoa1903212 Vichinsky et al. 2019 (HOPE)] | ||
− | |rowspan=2|2017-2018 | + | |rowspan=2|2017-01 to 2018-05 |
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |1. Placebo | + | |1. [[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]] |
− | | style="background-color:#1a9850" |Superior hemoglobin response | + | | style="background-color:#1a9850" |Superior hemoglobin response (primary endpoint) |
|- | |- | ||
|2. [[#Voxelotor_monotherapy|Voxelotor]]; 900 mg/day | |2. [[#Voxelotor_monotherapy|Voxelotor]]; 900 mg/day | ||
Line 114: | Line 139: | ||
|} | |} | ||
''Note: no specific dose of hydroxyurea is specified, just that the dose had to be stable for at least 3 months prior to trial enrollment. Approximately two-thirds of the patients were noted to be on hydroxyurea at baseline.'' | ''Note: no specific dose of hydroxyurea is specified, just that the dose had to be stable for at least 3 months prior to trial enrollment. Approximately two-thirds of the patients were noted to be on hydroxyurea at baseline.'' | ||
− | ==== | + | <div class="toccolours" style="background-color:#f2f3f4"> |
+ | ====Chemotherapy==== | ||
*[[Hydroxyurea (Hydrea)]] | *[[Hydroxyurea (Hydrea)]] | ||
+ | ====Targeted therapy==== | ||
*[[Voxelotor (Oxbryta)]] 1500 mg PO once per day | *[[Voxelotor (Oxbryta)]] 1500 mg PO once per day | ||
+ | '''Continued indefinitely''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''HOPE:''' Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J; HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. Epub 2019 Jun 14. [https://doi.org/10.1056/nejmoa1903212 link to original article] ''' | + | # '''HOPE:''' Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J; HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. Epub 2019 Jun 14. [https://doi.org/10.1056/nejmoa1903212 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31199090/ PubMed] [https://clinicaltrials.gov/study/NCT03036813 NCT03036813] |
− | ## '''Update:''' Howard J, Ataga KI, Brown RC, Achebe M, Nduba V, El-Beshlawy A, Hassab H, Agodoa I, Tonda M, Gray S, Lehrer-Graiwer J, Vichinsky E. Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2021 | + | ## '''Update:''' Howard J, Ataga KI, Brown RC, Achebe M, Nduba V, El-Beshlawy A, Hassab H, Agodoa I, Tonda M, Gray S, Lehrer-Graiwer J, Vichinsky E. Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2021 May;8(5):e323-e333. Epub 2021 Apr 7. [https://doi.org/10.1016/s2352-3026(21)00059-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33838113/ PubMed] |
− | |||
==L-glutamine monotherapy {{#subobject:4eb49b|Regimen=1}}== | ==L-glutamine monotherapy {{#subobject:4eb49b|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:feca18|Variant=1}}=== | ===Regimen {{#subobject:feca18|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa1715971 Niihara et al. 2018 (GLUSCC09-01)] |
|2010-2013 | |2010-2013 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-switch-ooc) |
− | |Placebo +/- Hydroxyurea | + | |[[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]] +/- Hydroxyurea |
− | |style="background-color:#1a9850"|Superior reduction in the number of sickle cell crises through week 48 | + | |style="background-color:#1a9850"|Superior reduction in the number of sickle cell crises through week 48 (primary endpoint) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#f2f3f4"> | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[L-glutamine (Endari)]] 300 mg/kg PO twice per day | *[[L-glutamine (Endari)]] 300 mg/kg PO twice per day | ||
− | |||
'''48-week course''' | '''48-week course''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''GLUSCC09-01:''' Niihara Y, Miller ST, Kanter J, Lanzkron S, Smith WR, Hsu LL, Gordeuk VR, Viswanathan K, Sarnaik S, Osunkwo I, Guillaume E, Sadanandan S, Sieger L, Lasky JL, Panosyan EH, Blake OA, New TN, Bellevue R, Tran LT, Razon RL, Stark CW, Neumayr LD, Vichinsky EP; Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease. A phase 3 trial of l-glutamine in sickle cell disease. N Engl J Med. 2018 Jul 19;379(3):226-235. [https:// | + | # '''GLUSCC09-01:''' Niihara Y, Miller ST, Kanter J, Lanzkron S, Smith WR, Hsu LL, Gordeuk VR, Viswanathan K, Sarnaik S, Osunkwo I, Guillaume E, Sadanandan S, Sieger L, Lasky JL, Panosyan EH, Blake OA, New TN, Bellevue R, Tran LT, Razon RL, Stark CW, Neumayr LD, Vichinsky EP; Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease. A phase 3 trial of l-glutamine in sickle cell disease. N Engl J Med. 2018 Jul 19;379(3):226-235. [https://doi.org/10.1056/NEJMoa1715971 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30021096/ PubMed] [https://clinicaltrials.gov/study/NCT01179217 NCT01179217] |
==RBC transfusions== | ==RBC transfusions== | ||
− | + | <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;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 167: | Line 187: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195437/ DeBaun et al. 2014 (SIT)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195437/ DeBaun et al. 2014 (SIT)] | ||
|2004-2010 | |2004-2010 | ||
− | |style="background-color:#1a9851"|Phase | + | |style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |Observation | + | |[[Sickle_cell_anemia_-_null_regimens#Observation|Observation]] |
− | |style="background-color:#91cf60"|Seems to have fewer cerebral infarcts | + | |style="background-color:#91cf60"|Seems to have fewer cerebral infarcts (primary endpoint) |
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#f2f3f4"> | |
====Supportive therapy==== | ====Supportive therapy==== | ||
− | *RBC transfusions | + | *[[Red blood cells|RBC]] transfusions |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''SIT:''' DeBaun MR, Gordon M, McKinstry RC, Noetzel MJ, White DA, Sarnaik SA, Meier ER, Howard TH, Majumdar S, Inusa BP, Telfer PT, Kirby-Allen M, McCavit TL, Kamdem A, Airewele G, Woods GM, Berman B, Panepinto JA, Fuh BR, Kwiatkowski JL, King AA, Fixler JM, Rhodes MM, Thompson AA, Heiny ME, Redding-Lallinger RC, Kirkham FJ, Dixon N, Gonzalez CE, Kalinyak KA, Quinn CT, Strouse JJ, Miller JP, Lehmann H, Kraut MA, Ball WS Jr, Hirtz D, Casella JF. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med. 2014 Aug 21;371(8):699-710. [https:// | + | # '''SIT:''' DeBaun MR, Gordon M, McKinstry RC, Noetzel MJ, White DA, Sarnaik SA, Meier ER, Howard TH, Majumdar S, Inusa BP, Telfer PT, Kirby-Allen M, McCavit TL, Kamdem A, Airewele G, Woods GM, Berman B, Panepinto JA, Fuh BR, Kwiatkowski JL, King AA, Fixler JM, Rhodes MM, Thompson AA, Heiny ME, Redding-Lallinger RC, Kirkham FJ, Dixon N, Gonzalez CE, Kalinyak KA, Quinn CT, Strouse JJ, Miller JP, Lehmann H, Kraut MA, Ball WS Jr, Hirtz D, Casella JF. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med. 2014 Aug 21;371(8):699-710. [https://doi.org/10.1056/NEJMoa1401731 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4195437/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25140956/ PubMed] [https://clinicaltrials.gov/study/NCT00072761 NCT00072761] |
==Voxelotor monotherapy {{#subobject:4eb50c|Regimen=1}}== | ==Voxelotor monotherapy {{#subobject:4eb50c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:fug718|Variant=1}}=== | ===Regimen {{#subobject:fug718|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 193: | Line 211: | ||
|- | |- | ||
|rowspan=2|[https://doi.org/10.1056/nejmoa1903212 Vichinsky et al. 2019 (HOPE)] | |rowspan=2|[https://doi.org/10.1056/nejmoa1903212 Vichinsky et al. 2019 (HOPE)] | ||
− | |rowspan=2|2017-2018 | + | |rowspan=2|2017-01 to 2018-05 |
− | |rowspan=2 style="background-color:#1a9851"|Phase | + | |rowspan=2 style="background-color:#1a9851"|Phase 3 (E-esc) |
− | |1. Placebo | + | |1. [[Sickle_cell_anemia_-_null_regimens#Placebo|Placebo]] |
− | | style="background-color:#1a9850" |Superior hemoglobin response | + | | style="background-color:#1a9850" |Superior hemoglobin response (primary endpoint) |
|- | |- | ||
|2. [[#Voxelotor_monotherapy|Voxelotor]]; 900 mg/day | |2. [[#Voxelotor_monotherapy|Voxelotor]]; 900 mg/day | ||
Line 202: | Line 220: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#f2f3f4"> | ||
====Supportive therapy==== | ====Supportive therapy==== | ||
*[[Voxelotor (Oxbryta)]] 1500 mg PO once per day | *[[Voxelotor (Oxbryta)]] 1500 mg PO once per day | ||
− | + | '''Continued indefinitely''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''HOPE:''' Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J; HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. Epub 2019 Jun 14. [https://doi.org/10.1056/nejmoa1903212 link to original article] ''' | + | # '''HOPE:''' Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J; HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. Epub 2019 Jun 14. [https://doi.org/10.1056/nejmoa1903212 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31199090/ PubMed] [https://clinicaltrials.gov/study/NCT03036813 NCT03036813] |
− | ## '''Update:''' Howard J, Ataga KI, Brown RC, Achebe M, Nduba V, El-Beshlawy A, Hassab H, Agodoa I, Tonda M, Gray S, Lehrer-Graiwer J, Vichinsky E. Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2021 | + | ## '''Update:''' Howard J, Ataga KI, Brown RC, Achebe M, Nduba V, El-Beshlawy A, Hassab H, Agodoa I, Tonda M, Gray S, Lehrer-Graiwer J, Vichinsky E. Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2021 May;8(5):e323-e333. Epub 2021 Apr 7. [https://doi.org/10.1016/s2352-3026(21)00059-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33838113/ PubMed] |
− | |||
[[Category:Sickle cell anemia regimens]] | [[Category:Sickle cell anemia regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Hemolytic process]] | [[Category:Hemolytic process]] | ||
[[Category:Inherited hemoglobinopathies]] | [[Category:Inherited hemoglobinopathies]] |
Latest revision as of 02:03, 31 July 2024
Section editor | |
---|---|
Benjamin Tillman, MD Vanderbilt University Nashville, TN, USA |
Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
- We have moved How I Treat articles to a dedicated page.
6 regimens on this page
6 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASH
- 2021: Kanter et al. American Society of Hematology 2021 guidelines for sickle cell disease: stem cell transplantation link to PMC article PubMed
- 2020: Chou et al. American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support link to PMC article PubMed
- 2020: DeBaun et al. American Society of Hematology 2020 guidelines for sickle cell disease: prevention, diagnosis, and treatment of cerebrovascular disease in children and adults link to PMC article PubMed
- 2020: Brandow et al. American Society of Hematology 2020 guidelines for sickle cell disease: management of acute and chronic pain link to PMC article PubMed
- 2019: Liem et al. American Society of Hematology 2019 guidelines for sickle cell disease: cardiopulmonary and kidney disease link to PMC article PubMed
BSH
- 2021: Oteng-Ntim et al. Management of sickle cell disease in pregnancy. A British Society for Haematology Guideline PubMed
NHLBI
- 2014: Evidence-Based Management of Sickle Cell Disease: Expert Panel Report, 2014 link to PMC article PubMed
All lines of therapy
Crizanlizumab monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ataga et al. 2016 (SUSTAIN) | 2013-2015 | Randomized Phase 2 (E-RT-esc) | 1. Placebo | Superior annual rate of crises (primary endpoint) |
2. Crizanlizumab; 2.5 mg/kg | Not reported |
Supportive therapy
- Crizanlizumab (Adakveo) 5 mg/kg IV once on day 1
14-day cycle for 26 cycles (1 year)
References
- SUSTAIN: Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR, Gualandro S, Colella MP, Smith WR, Rollins SA, Stocker JW, Rother RP. Crizanlizumab for the prevention of pain crises in sickle cell disease. N Engl J Med. 2017 Feb 2;376(5):429-439. Epub 2016 Dec 3. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT01895361
Exagamglogene autotemcel monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Frangoul et al. 2024 (CLIMB SCD-121) | 2018-11-27 to not reported | Non-randomized phase 3 (RT) |
References
- CLIMB SCD-121: Frangoul H, Locatelli F, Sharma A, Bhatia M, Mapara M, Molinari L, Wall D, Liem RI, Telfer P, Shah AJ, Cavazzana M, Corbacioglu S, Rondelli D, Meisel R, Dedeken L, Lobitz S, de Montalembert M, Steinberg MH, Walters MC, Eckrich MJ, Imren S, Bower L, Simard C, Zhou W, Xuan F, Morrow PK, Hobbs WE, Grupp SA; CLIMB SCD-121 Study Group. Exagamglogene Autotemcel for Severe Sickle Cell Disease. N Engl J Med. 2024 May 9;390(18):1649-1662. Epub 2024 Apr 24. link to original article PubMed NCT03745287
Hydroxyurea monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Charache et al. 1995 (MSH) | 1992-1994 | Phase 3 (E-esc) | Placebo | Superior annual rate of crises |
Wang et al. 2011 (BABY HUG) | 2003-2009 | Phase 3 (E-esc) | Placebo | Did not meet co-primary endpoints of splenic and renal function |
Dose and schedule modifications
Doses were subsequently adjusted, see articles for details.
References
- MSH: Charache S, Terrin ML, Moore RD, Dover GJ, Barton FB, Eckert SV, McMahon RP, Bonds DR; Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. N Engl J Med. 1995 May 18;332(20):1317-22. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Update: Steinberg MH, Barton F, Castro O, Pegelow CH, Ballas SK, Kutlar A, Orringer E, Bellevue R, Olivieri N, Eckman J, Varma M, Ramirez G, Adler B, Smith W, Carlos T, Ataga K, DeCastro L, Bigelow C, Saunthararajah Y, Telfer M, Vichinsky E, Claster S, Shurin S, Bridges K, Waclawiw M, Bonds D, Terrin M. Effect of hydroxyurea on mortality and morbidity in adult sickle cell anemia: risks and benefits up to 9 years of treatment. JAMA. 2003 Apr 2;289(13):1645-51. Erratum in: JAMA. 2003 Aug 13;290(6):756. link to original article PubMed
- HRQoL analysis: Ballas SK, Barton FB, Waclawiw MA, Swerdlow P, Eckman JR, Pegelow CH, Koshy M, Barton BA, Bonds DR. Hydroxyurea and sickle cell anemia: effect on quality of life. Health Qual Life Outcomes. 2006 Aug 31;4:59. link to original article link to PMC article PubMed
- BABY HUG: Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW; BABY HUG investigators. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011 May 14;377(9778):1663-72. link to original article link to PMC article PubMed NCT00006400
- NOHARM MTD: John CC, Opoka RO, Latham TS, Hume HA, Nabaggala C, Kasirye P, Ndugwa CM, Lane A, Ware RE. Hydroxyurea Dose Escalation for Sickle Cell Anemia in Sub-Saharan Africa. N Engl J Med. 2020 Jun 25;382(26):2524-2533. link to original article PubMed NCT03128515
Hydroxyurea & Voxelotor
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vichinsky et al. 2019 (HOPE) | 2017-01 to 2018-05 | Phase 3 (E-esc) | 1. Placebo | Superior hemoglobin response (primary endpoint) |
2. Voxelotor; 900 mg/day | Not reported |
Note: no specific dose of hydroxyurea is specified, just that the dose had to be stable for at least 3 months prior to trial enrollment. Approximately two-thirds of the patients were noted to be on hydroxyurea at baseline.
References
- HOPE: Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J; HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. Epub 2019 Jun 14. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT03036813
- Update: Howard J, Ataga KI, Brown RC, Achebe M, Nduba V, El-Beshlawy A, Hassab H, Agodoa I, Tonda M, Gray S, Lehrer-Graiwer J, Vichinsky E. Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2021 May;8(5):e323-e333. Epub 2021 Apr 7. link to original article PubMed
L-glutamine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Niihara et al. 2018 (GLUSCC09-01) | 2010-2013 | Phase 3 (E-switch-ooc) | Placebo +/- Hydroxyurea | Superior reduction in the number of sickle cell crises through week 48 (primary endpoint) |
References
- GLUSCC09-01: Niihara Y, Miller ST, Kanter J, Lanzkron S, Smith WR, Hsu LL, Gordeuk VR, Viswanathan K, Sarnaik S, Osunkwo I, Guillaume E, Sadanandan S, Sieger L, Lasky JL, Panosyan EH, Blake OA, New TN, Bellevue R, Tran LT, Razon RL, Stark CW, Neumayr LD, Vichinsky EP; Investigators of the Phase 3 Trial of l-Glutamine in Sickle Cell Disease. A phase 3 trial of l-glutamine in sickle cell disease. N Engl J Med. 2018 Jul 19;379(3):226-235. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01179217
RBC transfusions
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
DeBaun et al. 2014 (SIT) | 2004-2010 | Phase 3 (E-esc) | Observation | Seems to have fewer cerebral infarcts (primary endpoint) |
Supportive therapy
- RBC transfusions
References
- SIT: DeBaun MR, Gordon M, McKinstry RC, Noetzel MJ, White DA, Sarnaik SA, Meier ER, Howard TH, Majumdar S, Inusa BP, Telfer PT, Kirby-Allen M, McCavit TL, Kamdem A, Airewele G, Woods GM, Berman B, Panepinto JA, Fuh BR, Kwiatkowski JL, King AA, Fixler JM, Rhodes MM, Thompson AA, Heiny ME, Redding-Lallinger RC, Kirkham FJ, Dixon N, Gonzalez CE, Kalinyak KA, Quinn CT, Strouse JJ, Miller JP, Lehmann H, Kraut MA, Ball WS Jr, Hirtz D, Casella JF. Controlled trial of transfusions for silent cerebral infarcts in sickle cell anemia. N Engl J Med. 2014 Aug 21;371(8):699-710. link to original article link to PMC article PubMed NCT00072761
Voxelotor monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Vichinsky et al. 2019 (HOPE) | 2017-01 to 2018-05 | Phase 3 (E-esc) | 1. Placebo | Superior hemoglobin response (primary endpoint) |
2. Voxelotor; 900 mg/day | Not reported |
References
- HOPE: Vichinsky E, Hoppe CC, Ataga KI, Ware RE, Nduba V, El-Beshlawy A, Hassab H, Achebe MM, Alkindi S, Brown RC, Diuguid DL, Telfer P, Tsitsikas DA, Elghandour A, Gordeuk VR, Kanter J, Abboud MR, Lehrer-Graiwer J, Tonda M, Intondi A, Tong B, Howard J; HOPE Trial Investigators. A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease. N Engl J Med. 2019 Aug 8;381(6):509-519. Epub 2019 Jun 14. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT03036813
- Update: Howard J, Ataga KI, Brown RC, Achebe M, Nduba V, El-Beshlawy A, Hassab H, Agodoa I, Tonda M, Gray S, Lehrer-Graiwer J, Vichinsky E. Voxelotor in adolescents and adults with sickle cell disease (HOPE): long-term follow-up results of an international, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Haematol. 2021 May;8(5):e323-e333. Epub 2021 Apr 7. link to original article PubMed