Difference between revisions of "Cold agglutinin disease"

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=Guidelines=
 
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=="How I Treat"==
 
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*'''2021:''' Berentsen [https://doi.org/10.1182/blood.2019003809 How I treat cold agglutinin disease]
 
 
=All lines of therapy=
 
=All lines of therapy=
 
==Bendamustine & Rituximab (BR) {{#subobject:0fde6d|Regimen=1}}==
 
==Bendamustine & Rituximab (BR) {{#subobject:0fde6d|Regimen=1}}==
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<div class="toccolours" style="background-color:#eeeeee">
 
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===Regimen {{#subobject:95a0a9|Variant=1}}===
 
===Regimen {{#subobject:95a0a9|Variant=1}}===
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{| class="wikitable" style="width: 40%; text-align:center;"  
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{| class="wikitable sortable" style="width: 60%; text-align:center;"  
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! style="width: 25%" |Study
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!style="width: 33%"|Study
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! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 33%"|Dates of enrollment
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!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
|-
 
|-
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6177646/ Röth et al. 2018 (DECADE)]
 
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6177646/ Röth et al. 2018 (DECADE)]
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| style="background-color:#ffffbe" |Phase 2, <20 pts
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|2011-01-06 to 2014-01-14
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====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
 
*[[Eculizumab (Soliris)]] as follows:
 
*[[Eculizumab (Soliris)]] as follows:
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**Cycle 1: 600 mg IV once per day on days 1, 8, 15, 22
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**Cycles 1 to 4: 600 mg IV once on day 1
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**Cycles 2 to 11: 900 mg IV once on day 1
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**Cycles 5 to 15: 900 mg IV once on day 1
 
====Supportive therapy====
 
====Supportive therapy====
 
*Patients were vaccinated against ''Neisseria meningitidis'' or received "appropriate antibiotics" if vaccination occurred within 14 days of the first dose
 
*Patients were vaccinated against ''Neisseria meningitidis'' or received "appropriate antibiotics" if vaccination occurred within 14 days of the first dose
−
'''28-day cycle for 1 cycle, then 14-day cycle for 11 cycles'''
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'''7-day cycle for 4 cycles, then 14-day cycle for 11 cycles (26 weeks total)'''
 
</div></div>
 
</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] [https://pubmed.ncbi.nlm.nih.gov/30291112/ PubMed] [https://clinicaltrials.gov/study/NCT01303952 NCT01303952]
+
#'''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 (FR) {{#subobject:96c221|Regimen=1}}==
 
==Fludarabine & Rituximab (FR) {{#subobject:96c221|Regimen=1}}==
 
FR: '''<u>F</u>'''ludarabine & '''<u>R</u>'''ituximab
 
FR: '''<u>F</u>'''ludarabine & '''<u>R</u>'''ituximab
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<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
 
===Regimen===
 
===Regimen===
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{| class="wikitable" style="width: 60%; text-align:center;"  
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{| class="wikitable sortable" style="width: 100%; text-align:center;"  
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! style="width: 33%" |Study
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!style="width: 20%"|Study
−
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 20%"|Dates of enrollment
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! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
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!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
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!style="width: 20%"|Comparator
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!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
 
|[https://doi.org/10.1056/nejmoa2027760 Röth et al. 2021 (CARDINAL)]
 
|[https://doi.org/10.1056/nejmoa2027760 Röth et al. 2021 (CARDINAL)]
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| style="background-color:#91cf61" |Phase 2
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|NR
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| style="background-color:#91cf61" |Phase 2 (RT)
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| style="background-color:#d3d3d3" |
 
| style="background-color:#9ebcda" |ORR: 54%
 
| style="background-color:#9ebcda" |ORR: 54%
 +
|-
 +
|[https://doi.org/10.1182/blood.2021014955 Röth et al. 2022 (CADENZA)]
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|2018-03-06 to 2020-09-29
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| style="background-color:#1a9851" |Phase 3 (E-esc)
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|Placebo
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| style="background-color:#1a9850" |Superior composite primary endpoint
 
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====Immunosuppressive therapy====
 
====Immunosuppressive therapy====
 
*[[Sutimlimab (Enjaymo)]] by the following weight-based criteria:  
 
*[[Sutimlimab (Enjaymo)]] by the following weight-based criteria:  
−
**Patients who weighed less than 75 kg at baseline: 6500 mg IV once on day 1
+
**Less than 75 kg: 6500 mg IV once on day 1
−
**Patients who weighed 75 kg or more: 7500 mg IV once on day 1
+
**75 kg or more: 7500 mg IV once on day 1
−
'''7-day cycle, then 14-day cycle for 12 cycles (26 weeks)'''
+
'''7-day course, then 14-day cycle for 12 cycles (26 weeks)'''
 
</div></div>
 
</div></div>
 +
 
===References===
 
===References===
 
#'''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]
 
#'''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]
 
#'''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]
 
#'''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]
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=Investigational agents=
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−
*[[Sutimlimab (BIVV009)]]
 
 
[[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]]
 
[[Category:Hemolytic process]]

Latest 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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