Difference between revisions of "Cold agglutinin disease"

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Is there a regimen missing from this list?  Would you like to share a different dosage/schedule or an additional reference for a regimen?  Have you noticed an error?  Do you have an idea that will help the site grow to better meet your needs and the needs of many others?  You are [[How_to_contribute|invited to contribute to the site]].
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[[#top|Back to Top]]
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{{#lst:Editorial board transclusions|heme}}
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*''We have moved [[How I Treat]] articles to a dedicated page.''
 
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|<div style="background-color: #66FF66; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} regimens on this page</b></font></div>
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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<div style="background-color: #66CCFF; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} variants on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
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=All lines of therapy=
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=All lines of treatment=
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==Bendamustine & Rituximab (BR) {{#subobject:0fde6d|Regimen=1}}==
−
 
 
−
==BR {{#subobject:0fde6d|Regimen=1}}==
 
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{| class="wikitable" style="float:right; margin-left: 5px;"
 
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|-
 
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|[[#top|back to top]]
 
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BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 
BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:47595c|Variant=1}}===
 
===Regimen {{#subobject:47595c|Variant=1}}===
−
{| border="1" style="text-align:center;" !align="left"  
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{| class="wikitable" style="width: 40%; text-align:center;"  
−
|'''Study'''
+
! style="width: 25%" |Study
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
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! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/130/4/537.long Berentsen et al. 2017]
+
|[http://www.bloodjournal.org/content/130/4/537.long Berentsen et al. 2017 (CAD5)]
−
|style="background-color:#eeee00"|Phase II
+
| style="background-color:#91cf61" |Phase 2
 
|-
 
|-
 
|}
 
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
 +
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 +
====Targeted therapy====
 
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
 
−
 
 
'''28-day cycle for 4 cycles'''
 
'''28-day cycle for 4 cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# Berentsen S, Randen U, Oksman M, Birgens H, Tvedt THA, Dalgaard J, Galteland E, Haukås E, Brudevold R, Sørbø JH, Næss IA, Malecka A, Tjønnfjord GE. Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial. Blood. 2017 Jul 27;130(4):537-541. Epub 2017 May 22. [http://www.bloodjournal.org/content/130/4/537.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28533306 PubMed]
+
#'''CAD5:''' Berentsen S, Randen U, Oksman M, Birgens H, Tvedt THA, Dalgaard J, Galteland E, Haukås E, Brudevold R, Sørbø JH, Næss IA, Malecka A, Tjønnfjord GE. Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial. Blood. 2017 Jul 27;130(4):537-541. Epub 2017 May 22. [http://www.bloodjournal.org/content/130/4/537.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28533306/ PubMed] [https://clinicaltrials.gov/study/NCT02689986 NCT02689986]
−
 
 
−
==Eculizumab (Soliris) {{#subobject:08ef07|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
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|[[#top|back to top]]
 
−
|}
 
  
 +
==Eculizumab monotherapy {{#subobject:08ef07|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:95a0a9|Variant=1}}===
 
===Regimen {{#subobject:95a0a9|Variant=1}}===
−
{| border="1" style="text-align:center;" !align="left"  
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{| class="wikitable sortable" style="width: 60%; text-align:center;"  
−
|'''Study'''
+
!style="width: 33%"|Study
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
!style="width: 33%"|Dates of enrollment
 +
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
−
|[https://ash.confex.com/ash/2015/webprogram/Paper79420.html Röth et al. 2015 (DECADE)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6177646/ Röth et al. 2018 (DECADE)]
−
|style="background-color:#ff0000"|Phase II, <20 pts
+
|2011-01-06 to 2014-01-14
 +
| style="background-color:#ffffbe" |Phase 2, fewer than 20 pts
 
|-
 
|-
 
|}
 
|}
−
 
+
''Note: Eligible patients had symptomatic cold agglutinin-mediated hemolysis with a serum lactate dehydrogenase (LDH) level greater than or equal to 2 x upper limit of normal and a cold agglutinin titer greater than 1:64 at 4°C.''
−
''Eligible patients had symptomatic cold agglutinin-mediated hemolysis with a serum lactate dehydrogenase (LDH) level greater than or equal to 2 x upper limit of normal and a cold agglutinin titer greater than 1:64 at 4°C.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
 
+
====Immunosuppressive therapy====
−
*[[Eculizumab (Soliris)]] 600 mg IV once per week for 4 weeks, then 900 mg IV once on week 5, then 900 mg IV every 2 weeks
+
*[[Eculizumab (Soliris)]] as follows:
−
 
+
**Cycles 1 to 4: 600 mg IV once on day 1
−
Supportive medications:
+
**Cycles 5 to 15: 900 mg IV once on day 1
−
* Patients were vaccinated against ''Neisseria meningitidis'' or received "appropriate antibiotics" if vaccination occurred within 14 days of the first dose
+
====Supportive therapy====
−
 
+
*Patients were vaccinated against ''Neisseria meningitidis'' or received "appropriate antibiotics" if vaccination occurred within 14 days of the first dose
−
'''26-week course'''
+
'''7-day cycle for 4 cycles, then 14-day cycle for 11 cycles (26 weeks total)'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# '''Abstract:''' Alexander Röth, MD, Martin Bommer, MD, Andreas Hüttmann, MD, Dörte Herich-Terhürne, Nils Kuklik, PhD, Lenz Veronika, Hubert Schrezenmeier, MD and Ulrich Dührsen, MD. Complement Inhibition with Eculizumab in Patients with Cold Agglutinin Disease (CAD): Results from a Prospective Phase II Trial (DECADE Trial). ASH Annual Meeting 2015 Abstract 274 [https://ash.confex.com/ash/2015/webprogram/Paper79420.html link to abstract]
+
<!-- # '''Abstract:''' Alexander Röth, MD, Martin Bommer, MD, Andreas Hüttmann, MD, Dörte Herich-Terhürne, Nils Kuklik, PhD, Lenz Veronika, Hubert Schrezenmeier, MD and Ulrich Dührsen, MD. Complement Inhibition with Eculizumab in Patients with Cold Agglutinin Disease (CAD): Results from a Prospective Phase II Trial (DECADE Trial). ASH Annual Meeting 2015 Abstract 274 [https://ash.confex.com/ash/2015/webprogram/Paper79420.html link to abstract] -->
−
 
+
#'''DECADE:''' Röth A, Bommer M, Hüttmann A, Herich-Terhürne D, Kuklik N, Rekowski J, Lenz V, Schrezenmeier H, Dührsen U. Eculizumab in cold agglutinin disease (DECADE): an open-label, prospective, bicentric, nonrandomized phase 2 trial. Blood Adv. 2018 Oct 9;2(19):2543-2549. [https://doi.org/10.1182/bloodadvances.2018024190 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6177646/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30291112/ PubMed] [https://clinicaltrials.gov/study/NCT01303952 NCT01303952]
−
==Fludarabine & Rituximab {{#subobject:96c221|Regimen=1}}==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
  
 +
==Fludarabine & Rituximab (FR) {{#subobject:96c221|Regimen=1}}==
 +
FR: '''<u>F</u>'''ludarabine & '''<u>R</u>'''ituximab
 +
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen {{#subobject:645885|Variant=1}}===
 
===Regimen {{#subobject:645885|Variant=1}}===
−
{| border="1" style="text-align:center;" !align="left"  
+
{| class="wikitable" style="width: 60%; text-align:center;"  
−
|'''Study'''
+
! style="width: 33%" |Study
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
 
|[http://www.bloodjournal.org/content/116/17/3180.long Berentsen et al. 2010]
 
|[http://www.bloodjournal.org/content/116/17/3180.long Berentsen et al. 2010]
−
|style="background-color:#EEEE00"|Phase II
+
| style="background-color:#91cf61" |Phase 2
 +
| style="background-color:#e0ecf4" |ORR: 76%
 
|-
 
|-
 
|}
 
|}
−
 
+
''Note: Eligible patients had to be diagnosed with cold agglutinin disease and require therapy because of anemia, substantial cold-induced circulatory symptoms, or both.''
−
''Eligible patients had to be diagnosed with cold agglutinin disease and require therapy because of anemia, substantial cold-induced circulatory symptoms, or both.''
+
<div class="toccolours" style="background-color:#b3e2cd">
−
 
+
====Chemotherapy====
−
*[[Fludarabine (Fludara)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5, 29 to 34, 57 to 61, 85 to 89
+
*[[Fludarabine (Fludara)]] 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 29, 57, 85
+
====Targeted therapy====
−
 
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
−
'''One course'''
+
'''28-day cycle for 4 cycles'''
−
 
+
</div></div>
 
===References===
 
===References===
−
# Berentsen S, Randen U, Vågan AM, Hjorth-Hansen H, Vik A, Dalgaard J, Jacobsen EM, Thoresen AS, Beiske K, Tjønnfjord GE. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood. 2010 Oct 28;116(17):3180-4. Epub 2010 Jul 15. [http://www.bloodjournal.org/content/116/17/3180.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20634373 PubMed]
+
#Berentsen S, Randen U, Vågan AM, Hjorth-Hansen H, Vik A, Dalgaard J, Jacobsen EM, Thoresen AS, Beiske K, Tjønnfjord GE. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood. 2010 Oct 28;116(17):3180-4. Epub 2010 Jul 15. [http://www.bloodjournal.org/content/116/17/3180.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20634373/ PubMed] [https://clinicaltrials.gov/study/NCT00373594 NCT00373594]
−
 
 
 
==Rituximab monotherapy {{#subobject:65c6f1|Regimen=1}}==
 
==Rituximab monotherapy {{#subobject:65c6f1|Regimen=1}}==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:372fe5|Variant=1}}===
 +
{| class="wikitable" style="width: 60%; text-align:center;"  
 +
! style="width: 33%" |Study
 +
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|[http://www.bloodjournal.org/content/103/8/2925.long Berentsen et al. 2003]
 +
| style="background-color:#91cf61" |Phase 2
 +
| style="background-color:#9ebcda" |ORR: 54%
 +
|-
 +
|[https://doi.org/10.1080/10428190500286481 Schöllkopf et al. 2006]
 +
| style="background-color:#91cf61" |Phase 2
 +
| style="background-color:#8c96c6" |ORR: 45%
 
|-
 
|-
−
|[[#top|back to top]]
 
 
|}
 
|}
−
 
+
''Note: Patients in Berentsen et al. 2003 were required to have cold agglutinin disease, as defined by the combination of chronic hemolysis and a cold agglutinin titer of 1:64 or higher, and a typical pattern for the direct antiglobulin test (DAT).''
−
===Regimen {{#subobject:372fe5|Variant=1}}===
+
<div class="toccolours" style="background-color:#b3e2cd">
−
{| border="1" style="text-align:center;" !align="left"  
+
====Immunosuppressive therapy====
−
|'''Study'''
+
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
−
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+
'''28-day course'''
 +
</div></div>
 +
===References===
 +
#Berentsen S, Ulvestad E, Gjertsen BT, Hjorth-Hansen H, Langholm R, Knutsen H, Ghanima W, Shammas FV, Tjønnfjord GE. Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood. 2004 Apr 15;103(8):2925-8. Epub 2003 Dec 30. [http://www.bloodjournal.org/content/103/8/2925.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15070665/ PubMed]
 +
#Schöllkopf C, Kjeldsen L, Bjerrum OW, Mourits-Andersen HT, Nielsen JL, Christensen BE, Jensen BA, Pedersen BB, Taaning EB, Klausen TW, Birgens H. Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients. Leuk Lymphoma. 2006 Feb;47(2):253-60. [https://doi.org/10.1080/10428190500286481 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16321854/ PubMed]
 +
==Sutimlimab monotherapy==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen===
 +
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 +
!style="width: 20%"|Study
 +
!style="width: 20%"|Dates of enrollment
 +
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 20%"|Comparator
 +
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/103/8/2925.long Berentsen et al. 2003]
+
|[https://doi.org/10.1056/nejmoa2027760 Röth et al. 2021 (CARDINAL)]
−
|style="background-color:#EEEE00"|Phase II
+
|NR
 +
| style="background-color:#91cf61" |Phase 2 (RT)
 +
| style="background-color:#d3d3d3" |
 +
| style="background-color:#9ebcda" |ORR: 54%
 
|-
 
|-
−
|[http://www.tandfonline.com/doi/full/10.1080/10428190500286481 Schöllkopf et al. 2006]
+
|[https://doi.org/10.1182/blood.2021014955 Röth et al. 2022 (CADENZA)]
−
|style="background-color:#EEEE00"|Phase II
+
|2018-03-06 to 2020-09-29
 +
| style="background-color:#1a9851" |Phase 3 (E-esc)
 +
|Placebo
 +
| style="background-color:#1a9850" |Superior composite primary endpoint
 
|-
 
|-
 
|}
 
|}
−
 
+
<div class="toccolours" style="background-color:#b3e2cd">
−
''Patients in '''Berentsen et al. 2003''' were required to have cold agglutinin disease, as defined by the combination of chronic hemolysis and a cold agglutinin titer of 1:64 or higher, and a typical pattern for the direct antiglobulin test (DAT).''
+
====Immunosuppressive therapy====
−
 
+
*[[Sutimlimab (Enjaymo)]] by the following weight-based criteria:
−
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per week
+
**Less than 75 kg: 6500 mg IV once on day 1
−
 
+
**75 kg or more: 7500 mg IV once on day 1
−
'''4-week course'''
+
'''7-day course, then 14-day cycle for 12 cycles (26 weeks)'''
 +
</div></div>
  
 
===References===
 
===References===
−
# Berentsen S, Ulvestad E, Gjertsen BT, Hjorth-Hansen H, Langholm R, Knutsen H, Ghanima W, Shammas FV, Tjønnfjord GE. Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood. 2004 Apr 15;103(8):2925-8. Epub 2003 Dec 30. [http://www.bloodjournal.org/content/103/8/2925.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15070665 PubMed]
+
#'''CARDINAL:''' Röth A, Barcellini W, D'Sa S, Miyakawa Y, Broome CM, Michel M, Kuter DJ, Jilma B, Tvedt THA, Fruebis J, Jiang X, Lin S, Reuter C, Morales-Arias J, Hobbs W, Berentsen S. Sutimlimab in Cold Agglutinin Disease. N Engl J Med. 2021 Apr 8;384(14):1323-1334. [https://doi.org/10.1056/nejmoa2027760 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33826820/ PubMed] [https://clinicaltrials.gov/study/NCT03347396 NCT03347396]
−
# Schöllkopf C, Kjeldsen L, Bjerrum OW, Mourits-Andersen HT, Nielsen JL, Christensen BE, Jensen BA, Pedersen BB, Taaning EB, Klausen TW, Birgens H. Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients. Leuk Lymphoma. 2006 Feb;47(2):253-60. [http://www.tandfonline.com/doi/full/10.1080/10428190500286481 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16321854 PubMed]
+
#'''CADENZA:''' Röth A, Berentsen S, Barcellini W, D'Sa S, Jilma B, Michel M, Weitz IC, Yamaguchi M, Nishimura JI, Vos JMI, Storek M, Wong N, Patel P, Jiang X, Vagge DS, Wardęcki M, Shafer F, Lee M, Broome CM. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial. Blood. 2022 Sep 1;140(9):980-991. [https://doi.org/10.1182/blood.2021014955 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35687757/ PubMed] [https://clinicaltrials.gov/study/NCT03347422 NCT03347422]
  
 
[[Category:Cold agglutinin disease regimens]]
 
[[Category:Cold agglutinin disease regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
 
[[Category:Complementopathies]]
 
[[Category:Complementopathies]]
 +
[[Category:Hemolytic process]]

Revision as of 11:32, 15 May 2024

Back to Top

Section editor
Tillman Benjamin-2.jpg
 Benjamin Tillman, MD
Vanderbilt University
Nashville, TN, USA
LinkedIn
  • We have moved How I Treat articles to a dedicated page.
4 regimens on this page
4 variants on this page


All lines of therapy

Bendamustine & Rituximab (BR)

BR: Bendamustine, Rituximab

Regimen

Study Evidence
Berentsen et al. 2017 (CAD5) Phase 2

Chemotherapy

Targeted therapy

28-day cycle for 4 cycles

References

  1. CAD5: Berentsen S, Randen U, Oksman M, Birgens H, Tvedt THA, Dalgaard J, Galteland E, Haukås E, Brudevold R, Sørbø JH, Næss IA, Malecka A, Tjønnfjord GE. Bendamustine plus rituximab for chronic cold agglutinin disease: results of a Nordic prospective multicenter trial. Blood. 2017 Jul 27;130(4):537-541. Epub 2017 May 22. link to original article contains dosing details in manuscript PubMed NCT02689986

Eculizumab monotherapy

Regimen

Study Dates of enrollment Evidence
Röth et al. 2018 (DECADE) 2011-01-06 to 2014-01-14 Phase 2, fewer than 20 pts

Note: Eligible patients had symptomatic cold agglutinin-mediated hemolysis with a serum lactate dehydrogenase (LDH) level greater than or equal to 2 x upper limit of normal and a cold agglutinin titer greater than 1:64 at 4°C.

Immunosuppressive therapy

  • Eculizumab (Soliris) as follows:
    • Cycles 1 to 4: 600 mg IV once on day 1
    • Cycles 5 to 15: 900 mg IV once on day 1

Supportive therapy

  • Patients were vaccinated against Neisseria meningitidis or received "appropriate antibiotics" if vaccination occurred within 14 days of the first dose

7-day cycle for 4 cycles, then 14-day cycle for 11 cycles (26 weeks total)

References

  1. DECADE: Röth A, Bommer M, Hüttmann A, Herich-Terhürne D, Kuklik N, Rekowski J, Lenz V, Schrezenmeier H, Dührsen U. Eculizumab in cold agglutinin disease (DECADE): an open-label, prospective, bicentric, nonrandomized phase 2 trial. Blood Adv. 2018 Oct 9;2(19):2543-2549. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01303952

Fludarabine & Rituximab (FR)

FR: Fludarabine & Rituximab

Regimen

Study Evidence Efficacy
Berentsen et al. 2010 Phase 2 ORR: 76%

Note: Eligible patients had to be diagnosed with cold agglutinin disease and require therapy because of anemia, substantial cold-induced circulatory symptoms, or both.

Chemotherapy

Targeted therapy

28-day cycle for 4 cycles

References

  1. Berentsen S, Randen U, Vågan AM, Hjorth-Hansen H, Vik A, Dalgaard J, Jacobsen EM, Thoresen AS, Beiske K, Tjønnfjord GE. High response rate and durable remissions following fludarabine and rituximab combination therapy for chronic cold agglutinin disease. Blood. 2010 Oct 28;116(17):3180-4. Epub 2010 Jul 15. link to original article contains dosing details in manuscript PubMed NCT00373594

Rituximab monotherapy

Regimen

Study Evidence Efficacy
Berentsen et al. 2003 Phase 2 ORR: 54%
Schöllkopf et al. 2006 Phase 2 ORR: 45%

Note: Patients in Berentsen et al. 2003 were required to have cold agglutinin disease, as defined by the combination of chronic hemolysis and a cold agglutinin titer of 1:64 or higher, and a typical pattern for the direct antiglobulin test (DAT).

Immunosuppressive therapy

28-day course

References

  1. Berentsen S, Ulvestad E, Gjertsen BT, Hjorth-Hansen H, Langholm R, Knutsen H, Ghanima W, Shammas FV, Tjønnfjord GE. Rituximab for primary chronic cold agglutinin disease: a prospective study of 37 courses of therapy in 27 patients. Blood. 2004 Apr 15;103(8):2925-8. Epub 2003 Dec 30. link to original article contains dosing details in manuscript PubMed
  2. Schöllkopf C, Kjeldsen L, Bjerrum OW, Mourits-Andersen HT, Nielsen JL, Christensen BE, Jensen BA, Pedersen BB, Taaning EB, Klausen TW, Birgens H. Rituximab in chronic cold agglutinin disease: a prospective study of 20 patients. Leuk Lymphoma. 2006 Feb;47(2):253-60. link to original article contains dosing details in abstract PubMed

Sutimlimab monotherapy

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Röth et al. 2021 (CARDINAL) NR Phase 2 (RT) ORR: 54%
Röth et al. 2022 (CADENZA) 2018-03-06 to 2020-09-29 Phase 3 (E-esc) Placebo Superior composite primary endpoint

Immunosuppressive therapy

  • Sutimlimab (Enjaymo) by the following weight-based criteria:
    • Less than 75 kg: 6500 mg IV once on day 1
    • 75 kg or more: 7500 mg IV once on day 1

7-day course, then 14-day cycle for 12 cycles (26 weeks)

References

  1. CARDINAL: Röth A, Barcellini W, D'Sa S, Miyakawa Y, Broome CM, Michel M, Kuter DJ, Jilma B, Tvedt THA, Fruebis J, Jiang X, Lin S, Reuter C, Morales-Arias J, Hobbs W, Berentsen S. Sutimlimab in Cold Agglutinin Disease. N Engl J Med. 2021 Apr 8;384(14):1323-1334. link to original article PubMed NCT03347396
  2. CADENZA: Röth A, Berentsen S, Barcellini W, D'Sa S, Jilma B, Michel M, Weitz IC, Yamaguchi M, Nishimura JI, Vos JMI, Storek M, Wong N, Patel P, Jiang X, Vagge DS, Wardęcki M, Shafer F, Lee M, Broome CM. Sutimlimab in patients with cold agglutinin disease: results of the randomized placebo-controlled phase 3 CADENZA trial. Blood. 2022 Sep 1;140(9):980-991. link to original article PubMed NCT03347422
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