Difference between revisions of "Langerhans cell histiocytosis"
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''Note: the majority of the regimens on this page are intended for multi-system Langerhans cell histiocytosis (MS-LCH); many patients with other forms of LCH, such as pulmonary (PLCH) do not necessarily need antineoplastic treatment.'' | ''Note: the majority of the regimens on this page are intended for multi-system Langerhans cell histiocytosis (MS-LCH); many patients with other forms of LCH, such as pulmonary (PLCH) do not necessarily need antineoplastic treatment.'' | ||
=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.''' | ||
==[https://www.eurohistio.net/index_eng.html Euro-Histio-Net]== | ==[https://www.eurohistio.net/index_eng.html Euro-Histio-Net]== | ||
− | *'''2013:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667012/ Management of adult patients with Langerhans cell histiocytosis: Recommendations from an expert panel on behalf of Euro-Histio-Net] | + | |
− | *'''2013:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557042/ Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years] | + | *'''2013:''' Girschikofsky et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3667012/ Management of adult patients with Langerhans cell histiocytosis: Recommendations from an expert panel on behalf of Euro-Histio-Net] [https://pubmed.ncbi.nlm.nih.gov/23672541/ PubMed] |
+ | *'''2013:''' Haupt et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4557042/ Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years] [https://www.ncbi.nlm.nih.gov/pubmed/23109216 PubMed] | ||
+ | |||
+ | ==International Expert Consensus== | ||
+ | *'''2022:''' Goyal et al. [https://doi.org/10.1182/blood.2021014343 International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults] [https://www.ncbi.nlm.nih.gov/pubmed/35271698 PubMed] | ||
==[https://www.nccn.org NCCN]== | ==[https://www.nccn.org NCCN]== | ||
− | *[https://www.nccn.org/ | + | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1502 NCCN Guidelines - Histiocytic Neoplasms].'' |
=Untreated= | =Untreated= | ||
− | |||
==Cytarabine & Methotrexate (CYM) {{#subobject:b24b28|Regimen=1}}== | ==Cytarabine & Methotrexate (CYM) {{#subobject:b24b28|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CYM: '''<u>CY</u>'''tarabine, '''<u>M</u>'''ethotrexate | CYM: '''<u>CY</u>'''tarabine, '''<u>M</u>'''ethotrexate | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:d51545|Variant=1}}=== | ===Regimen {{#subobject:d51545|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
Line 40: | Line 39: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 500 mg/m<sup>2</sup>) | *[[Cytarabine (Ara-C)]] 100 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 500 mg/m<sup>2</sup>) | ||
*[[Methotrexate (MTX)]] 1000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | *[[Methotrexate (MTX)]] 1000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1 | ||
− | |||
'''35-day cycle for 6 cycles''' | '''35-day cycle for 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #'''MAALCH:''' Cao XX, Li J, Zhao AL, He TH, Gao XM, Cai HC, Zhang L, Zhang Y, Feng J, Zhu TN, Niu N, Sun J, Liang ZY, Duan MH, Zhou DB. Methotrexate and cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis: A single arm, single center, prospective phase 2 study. Am J Hematol. 2020 Sep;95(9):E235-E238. Epub 2020 Jun 20. [https://doi.org/10.1002/ajh.25864 link to original article] '''contains | + | #'''MAALCH:''' Cao XX, Li J, Zhao AL, He TH, Gao XM, Cai HC, Zhang L, Zhang Y, Feng J, Zhu TN, Niu N, Sun J, Liang ZY, Duan MH, Zhou DB. Methotrexate and cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis: A single arm, single center, prospective phase 2 study. Am J Hematol. 2020 Sep;95(9):E235-E238. Epub 2020 Jun 20. [https://doi.org/10.1002/ajh.25864 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32395858/ PubMed] [https://clinicaltrials.gov/study/NCT02389400 NCT02389400] |
− | |||
==Etoposide & Prednisone {{#subobject:566a87|Regimen=1}}== | ==Etoposide & Prednisone {{#subobject:566a87|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:#3c6b84|Variant=1}}=== | ===Regimen {{#subobject:#3c6b84|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://doi.org/10.1067/mpd.2001.111331 Gadner et al. 2001 (LCH-I)] |
|1991-1995 | |1991-1995 | ||
|style="background-color:#1a9851"|Phase 3 (E-switch-ic) | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
Line 70: | Line 64: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Etoposide (Vepesid)]] | + | *[[Etoposide (Vepesid)]] 150 mg/mg<sup>2</sup> IV once per day on days 1 to 3 |
− | *[[Prednisone (Sterapred)]] | + | ====Glucocorticoid therapy==== |
− | + | *[[Prednisone (Sterapred)]] as follows: | |
+ | **Cycles 1: (dose/route not specified) once | ||
+ | '''21-day cycle for 8 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. [ | + | # Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. [https://doi.org/10.1067/mpd.2001.111331 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11343051/ PubMed] |
==Etoposide, Vinblastine, Prednisone {{#subobject:5145a8|Regimen=1}}== | ==Etoposide, Vinblastine, Prednisone {{#subobject:5145a8|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:#7ace0e|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://doi.org/10.1182/blood-2007-08-106211 Gadner et al. 2007 (LCH-II)] |
|1996-2001 | |1996-2001 | ||
|style="background-color:#1a9851"|Phase 3 (E-esc) | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
Line 99: | Line 92: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ====Chemotherapy | + | ====Chemotherapy==== |
− | *[[Etoposide (Vepesid)]] 150 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36 | + | *[[Etoposide (Vepesid)]] as follows: |
− | *[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36 | + | **Cycle 1: 150 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36 |
− | * | + | **Cycles 2 to 7: 150 mg/m<sup>2</sup> IV over 60 minutes once on day 1 |
− | + | *[[Vinblastine (Velban)]] as follows: | |
− | + | **Cycle 1: 6 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36 | |
− | + | **Cycles 2 to 7: 6 mg/m<sup>2</sup> IV bolus once on day 1 | |
− | ==== | + | ====Glucocorticoid therapy==== |
− | *[[ | + | *[[Prednisone (Sterapred)]] as follows: |
− | * | + | **Cycle 1: 40 mg/m<sup>2</sup>/day split three times per day for 4 weeks, then tapering off over 2 weeks |
− | * | + | **Cycles 2 to 7: 40 mg/m<sup>2</sup>/day split three times per day on days 1 to 5 |
− | + | '''6-week course, then 21-day cycle for 6 cycles''' | |
− | '''21-day cycle for 6 cycles''' | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | # '''LCH-II:''' Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. [ | + | # '''LCH-II:''' Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. [https://doi.org/10.1182/blood-2007-08-106211 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18089850/ PubMed] ISRCTN57679341 |
− | |||
==Methotrexate, Vinblastine, Prednisone {{#subobject:2d772c|Regimen=1}}== | ==Methotrexate, Vinblastine, Prednisone {{#subobject:2d772c|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:#f569ce|Variant=1}}=== | ===Regimen {{#subobject:#f569ce|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://doi.org/10.1182/blood-2012-09-455774 Gadner et al. 2013 (LCH-III)] |
|2001-2008 | |2001-2008 | ||
|style="background-color:#1a9851"|Phase 3 (E-esc) | |style="background-color:#1a9851"|Phase 3 (E-esc) | ||
Line 138: | Line 125: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Methotrexate (MTX)]] | + | *[[Methotrexate (MTX)]] 500 mg/m<sup>2</sup> IV once per day on days 1, 15, 29 |
− | *[[Vinblastine (Velban)]] | + | *[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36 |
− | *[[Prednisone (Sterapred)]] | + | ====Glucocorticoid therapy==== |
− | + | *[[Prednisone (Sterapred)]] 40 mg/m<sup>2</sup>/day PO on days 1 to 28, then tapered off by day 42 | |
+ | '''6-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Subsequent treatment==== | ||
+ | *See paper for details of treatment beyond induction. | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''LCH-III:''' Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. [ | + | # '''LCH-III:''' Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. [https://doi.org/10.1182/blood-2012-09-455774 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23589673/ PubMed] [https://clinicaltrials.gov/study/NCT00276757 NCT00276757] |
==Vinblastine & Prednisone {{#subobject:378322|Regimen=1}}== | ==Vinblastine & Prednisone {{#subobject:378322|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:#bf6a74|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://doi.org/10.1067/mpd.2001.111331 Gadner et al. 2001 (LCH-I)] |
|1991-1995 | |1991-1995 | ||
|style="background-color:#1a9851"|Phase 3 (E-switch-ic) | |style="background-color:#1a9851"|Phase 3 (E-switch-ic) | ||
Line 167: | Line 156: | ||
|style="background-color:#ffffbf"|Did not meet efficacy endpoints | |style="background-color:#ffffbf"|Did not meet efficacy endpoints | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2007-08-106211 Gadner et al. 2007 (LCH-II)] |
|1996-2001 | |1996-2001 | ||
|style="background-color:#1a9851"|Phase 3 (C) | |style="background-color:#1a9851"|Phase 3 (C) | ||
Line 173: | Line 162: | ||
|style="background-color:#ffffbf"|Did not meet primary endpoint of rapid response | |style="background-color:#ffffbf"|Did not meet primary endpoint of rapid response | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1182/blood-2012-09-455774 Gadner et al. 2013 (LCH-III)] |
|2001-2008 | |2001-2008 | ||
|style="background-color:#1a9851"|Phase 3 (C) | |style="background-color:#1a9851"|Phase 3 (C) | ||
Line 180: | Line 169: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ====Chemotherapy | + | ====Chemotherapy==== |
− | *[[Vinblastine (Velban)]] 6 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36 | + | *[[Vinblastine (Velban)]] as follows: |
− | * | + | **Cycle 1: 6 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36 |
− | + | **Cycles 2 to 7: 6 mg/m<sup>2</sup> IV bolus once on day 1 | |
− | + | ====Glucocorticoid therapy==== | |
− | + | *[[Prednisone (Sterapred)]] as follows: | |
− | ==== | + | **Cycle 1: 40 mg/m<sup>2</sup>/day split three times per day for 4 weeks, then tapering off over 2 weeks |
− | *[[ | + | **Cycles 2 to 7: 40 mg/m<sup>2</sup>/day split three times per day on days 1 to 5 |
− | * | + | '''6-week course, then 21-day cycle for 6 cycles''' |
− | + | </div></div> | |
− | '''21-day cycle for 6 cycles''' | ||
− | |||
===References=== | ===References=== | ||
− | # '''LCH-I:''' Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. [ | + | # '''LCH-I:''' Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. [https://doi.org/10.1067/mpd.2001.111331 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11343051/ PubMed] |
− | # '''LCH-II:''' Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. [ | + | # '''LCH-II:''' Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. [https://doi.org/10.1182/blood-2007-08-106211 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18089850/ PubMed] ISRCTN57679341 |
− | # '''LCH-III:''' Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. [ | + | # '''LCH-III:''' Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. [https://doi.org/10.1182/blood-2012-09-455774 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23589673/ PubMed] [https://clinicaltrials.gov/study/NCT00276757 NCT00276757] |
− | |||
=Relapsed or refractory= | =Relapsed or refractory= | ||
− | |||
==Cladribine monotherapy {{#subobject:da32fb|Regimen=1}}== | ==Cladribine monotherapy {{#subobject:da32fb|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:1ef1c0|Variant=1}}=== | ===Regimen {{#subobject:1ef1c0|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/pbc.22229 Weitzman et al. 2009 (LCH-S-98)] |
+ | |1999-04 to NR | ||
|style="background-color:#91cf61"|Phase 2 | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cladribine (Leustatin)]] | + | *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 5 |
− | + | '''21-day cycle for up to 6 cycles''' | |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''LCH-S-98:''' Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Pötschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH): results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. [https:// | + | # '''LCH-S-98:''' Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Pötschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH): results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. [https://doi.org/10.1002/pbc.22229 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19731321/ PubMed] |
==Cladribine & Cytarabine {{#subobject:4c5b41|Regimen=1}}== | ==Cladribine & Cytarabine {{#subobject:4c5b41|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:7b85e8|Variant=1}}=== | ===Regimen {{#subobject:7b85e8|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015 (LCH-S-2005)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015 (LCH-S-2005)] | ||
+ | |2005-04 to 2010-11 | ||
|style="background-color:#91cf61"|Phase 2 | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Cladribine (Leustatin)]] 9 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 6, '''should not be administered simultaneously with cytarabine''' | + | *[[Cladribine (Leustatin)]] by the following weight-based criteria: |
− | ** | + | **10 kg or more: 9 mg/m<sup>2</sup> IV over 2 hours once per day on days 2 to 6, '''should not be administered simultaneously with cytarabine''' |
+ | **Less than 10 kg: 0.3 mg/kg IV over 2 hours once per day on days 2 to 6, '''should not be administered simultaneously with cytarabine''' | ||
*[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup> IV over 2 hours twice per day on days 1 to 5, '''should not be administered simultaneously with cladribine''' | *[[Cytarabine (Ara-C)]] 500 mg/m<sup>2</sup> IV over 2 hours twice per day on days 1 to 5, '''should not be administered simultaneously with cladribine''' | ||
+ | '''35-day cycle for 2 or more cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
− | |||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | * | + | *LCH-S-2005, patients with a good response: [[#Cladribine_monotherapy_2|Cladribine]] consolidation |
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. --> | <!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. --> | ||
− | # '''LCH-S-2005:''' Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. [ | + | # '''LCH-S-2005:''' Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. [https://doi.org/10.1182/blood-2015-03-635151 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26194764/ PubMed] |
− | |||
==Cobimetinib monotherapy {{#subobject:a6f6dd|Regimen=1}}== | ==Cobimetinib monotherapy {{#subobject:a6f6dd|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:#fecb7f|Variant=1}}=== | ||
+ | {| class="wikitable" style="color:white; background-color:#404040" | ||
+ | |<small>'''FDA-recommended dose'''</small> | ||
|- | |- | ||
− | |||
|} | |} | ||
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | {| class="wikitable" style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
− | !style="width: | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438729/ Diamond et al. 2019 (MSK 15-216)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438729/ Diamond et al. 2019 (MSK 15-216)] | ||
− | |style="background-color:#ffffbe"| | + | |2016-NR |
+ | |style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in this arm (RT) | ||
|- | |- | ||
|} | |} | ||
''Note: there were N=2 patients with LCH; it was unclear if they were untreated or previously treated.'' | ''Note: there were N=2 patients with LCH; it was unclear if they were untreated or previously treated.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Cobimetinib (Cotellic)]] 60 mg PO once per day on days 1 to 21 | *[[Cobimetinib (Cotellic)]] 60 mg PO once per day on days 1 to 21 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''MSK 15-216:''' Diamond EL, Durham BH, Ulaner GA, Drill E, Buthorn J, Ki M, Bitner L, Cho H, Young RJ, Francis JH, Rampal R, Lacouture M, Brody LA, Ozkaya N, Dogan A, Rosen N, Iasonos A, Abdel-Wahab O, Hyman DM. Efficacy of MEK inhibition in patients with histiocytic neoplasms. Nature. 2019 Mar;567(7749):521-524. Epub 2019 Mar 13. [https:// | + | # '''MSK 15-216:''' Diamond EL, Durham BH, Ulaner GA, Drill E, Buthorn J, Ki M, Bitner L, Cho H, Young RJ, Francis JH, Rampal R, Lacouture M, Brody LA, Ozkaya N, Dogan A, Rosen N, Iasonos A, Abdel-Wahab O, Hyman DM. Efficacy of MEK inhibition in patients with histiocytic neoplasms. Nature. 2019 Mar;567(7749):521-524. Epub 2019 Mar 13. [https://doi.org/10.1038/s41586-019-1012-y link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6438729/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30867592/ PubMed] [https://clinicaltrials.gov/study/NCT02649972 NCT02649972] |
− | |||
==Vemurafenib monotherapy {{#subobject:953978|Regimen=1}}== | ==Vemurafenib monotherapy {{#subobject:953978|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
===Regimen {{#subobject:#73ec1b|Variant=1}}=== | ===Regimen {{#subobject:#73ec1b|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ Hyman et al. 2015 (VE-BASKET)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ Hyman et al. 2015 (VE-BASKET)] | ||
− | |style="background-color:#ffffbe"|Phase 2, | + | |2012-2014 |
+ | |style="background-color:#ffffbe"|Phase 2, fewer than 20 pts in this arm | ||
|- | |- | ||
|} | |} | ||
− | ''This was part of a basket trial, all patients had BRAF p.V600E mutations. A minority (7/18, 39%) of participants were untreated.'' | + | ''Note: This was part of a basket trial, all patients had BRAF p.V600E mutations. A minority (7/18, 39%) of participants were untreated.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Vemurafenib (Zelboraf)]] 960 mg PO twice per day | *[[Vemurafenib (Zelboraf)]] 960 mg PO twice per day | ||
− | |||
'''Duration of treatment not specified''' | '''Duration of treatment not specified''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''VE-BASKET:''' Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. [https:// | + | # '''VE-BASKET:''' Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. [https://doi.org/10.1056/NEJMoa1502309 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971773/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26287849/ PubMed] |
− | |||
=Relapsed or refractory, consolidation= | =Relapsed or refractory, consolidation= | ||
==Cladribine monotherapy {{#subobject:7db44f|Regimen=1}}== | ==Cladribine monotherapy {{#subobject:7db44f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:77d734|Variant=1}}=== | ===Regimen {{#subobject:77d734|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015 (LCH-S-2005)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015 (LCH-S-2005)] | ||
+ | |2005-04 to 2010-11 | ||
|style="background-color:#91cf61"|Phase 2 | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Cladribine_.26_Cytarabine|Cladribine & Cytarabine]] | + | *Salvage [[#Cladribine_.26_Cytarabine|Cladribine & Cytarabine]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 3 | *[[Cladribine (Leustatin)]] 5 mg/m<sup>2</sup> IV once per day on days 1 to 3 | ||
− | |||
'''21-day cycle for 2 cycles''' | '''21-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Mercaptopurine.2C_Methotrexate.2C_Vinblastine.2C_Prednisolone|4-drug | + | *[[#Mercaptopurine.2C_Methotrexate.2C_Vinblastine.2C_Prednisolone|4-drug]] maintenance |
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. --> | <!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. --> | ||
− | # '''LCH-S-2005:''' Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. [ | + | # '''LCH-S-2005:''' Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. [https://doi.org/10.1182/blood-2015-03-635151 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26194764/ PubMed] |
− | |||
=Relapsed or refractory, maintenance= | =Relapsed or refractory, maintenance= | ||
==Mercaptopurine, Methotrexate, Vinblastine, Prednisolone {{#subobject:b3e901|Regimen=1}}== | ==Mercaptopurine, Methotrexate, Vinblastine, Prednisolone {{#subobject:b3e901|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:231bee|Variant=1}}=== | ===Regimen {{#subobject:231bee|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | !style="width: | + | !style="width: 33%"|Study |
− | !style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015 (LCH-S-2005)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ Donadieu et al. 2015 (LCH-S-2005)] | ||
+ | |2005-04 to 2010-11 | ||
|style="background-color:#91cf61"|Phase 2 | |style="background-color:#91cf61"|Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Cladribine_monotherapy_2|Cladribine]] x 2 | + | *Salvage [[#Cladribine_monotherapy_2|Cladribine]] x 2 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Mercaptopurine (6-MP)]] 50 mg/m<sup>2</sup> PO once per day | + | *[[Mercaptopurine (6-MP)]] 50 mg/m<sup>2</sup> PO once per day on days 1 to 14 |
*[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once per day on days 1 & 8 | *[[Methotrexate (MTX)]] 20 mg/m<sup>2</sup> PO once per day on days 1 & 8 | ||
*[[Vinblastine (Velban)]] as follows: | *[[Vinblastine (Velban)]] as follows: | ||
**Cycles 1 to 13: 6 mg/m<sup>2</sup> IV once on day 1 | **Cycles 1 to 13: 6 mg/m<sup>2</sup> IV once on day 1 | ||
+ | ====Glucocorticoid therapy==== | ||
*[[Prednisolone (Millipred)]] as follows: | *[[Prednisolone (Millipred)]] as follows: | ||
**Cycles 1 to 13: 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 | **Cycles 1 to 13: 40 mg/m<sup>2</sup> PO once per day on days 1 to 5 | ||
− | + | '''14-day cycle for 39 cycles (18 months)''' | |
− | '''14-day | + | </div></div> |
− | |||
===References=== | ===References=== | ||
<!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. --> | <!-- Preliminary data from this study were presented orally at the 30th meeting of the Histiocyte Society, Washington, DC, 22 October 2013. --> | ||
− | # '''LCH-S-2005:''' Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. [ | + | # '''LCH-S-2005:''' Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. [https://doi.org/10.1182/blood-2015-03-635151 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624454/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26194764/ PubMed] |
− | |||
[[Category:Langerhans cell histiocytosis regimens]] | [[Category:Langerhans cell histiocytosis regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Histiocytoses]] | [[Category:Histiocytoses]] |
Revision as of 23:36, 24 June 2024
Section editor | |
---|---|
Gaurav Goyal, MD UAB Birmingham, AL, USA |
12 regimens on this page
12 variants on this page
|
Note: the majority of the regimens on this page are intended for multi-system Langerhans cell histiocytosis (MS-LCH); many patients with other forms of LCH, such as pulmonary (PLCH) do not necessarily need antineoplastic treatment.
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.
Euro-Histio-Net
- 2013: Girschikofsky et al. Management of adult patients with Langerhans cell histiocytosis: Recommendations from an expert panel on behalf of Euro-Histio-Net PubMed
- 2013: Haupt et al. Langerhans cell histiocytosis (LCH): Guidelines for diagnosis, clinical work-up, and treatment for patients till the age of 18 years PubMed
International Expert Consensus
- 2022: Goyal et al. International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults PubMed
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Histiocytic Neoplasms.
Untreated
Cytarabine & Methotrexate (CYM)
CYM: CYtarabine, Methotrexate
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Cao et al. 2020 (MAALCH) | 2014-2018 | Phase 2 |
Chemotherapy
- Cytarabine (Ara-C) 100 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 500 mg/m2)
- Methotrexate (MTX) 1000 mg/m2 IV continuous infusion over 24 hours, started on day 1
35-day cycle for 6 cycles
References
- MAALCH: Cao XX, Li J, Zhao AL, He TH, Gao XM, Cai HC, Zhang L, Zhang Y, Feng J, Zhu TN, Niu N, Sun J, Liang ZY, Duan MH, Zhou DB. Methotrexate and cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis: A single arm, single center, prospective phase 2 study. Am J Hematol. 2020 Sep;95(9):E235-E238. Epub 2020 Jun 20. link to original article contains dosing details in manuscript PubMed NCT02389400
Etoposide & Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gadner et al. 2001 (LCH-I) | 1991-1995 | Phase 3 (E-switch-ic) | Vinblastine & Prednisone | Did not meet efficacy endpoints |
Chemotherapy
- Etoposide (Vepesid) 150 mg/mg2 IV once per day on days 1 to 3
Glucocorticoid therapy
- Prednisone (Sterapred) as follows:
- Cycles 1: (dose/route not specified) once
21-day cycle for 8 cycles
References
- Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. link to original article contains dosing details in abstract PubMed
Etoposide, Vinblastine, Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gadner et al. 2007 (LCH-II) | 1996-2001 | Phase 3 (E-esc) | Vinblastine & Prednisone | Did not meet primary endpoint of rapid response |
Chemotherapy
- Etoposide (Vepesid) as follows:
- Cycle 1: 150 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
- Cycles 2 to 7: 150 mg/m2 IV over 60 minutes once on day 1
- Vinblastine (Velban) as follows:
- Cycle 1: 6 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36
- Cycles 2 to 7: 6 mg/m2 IV bolus once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) as follows:
- Cycle 1: 40 mg/m2/day split three times per day for 4 weeks, then tapering off over 2 weeks
- Cycles 2 to 7: 40 mg/m2/day split three times per day on days 1 to 5
6-week course, then 21-day cycle for 6 cycles
References
- LCH-II: Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. link to original article contains dosing details in manuscript PubMed ISRCTN57679341
Methotrexate, Vinblastine, Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gadner et al. 2013 (LCH-III) | 2001-2008 | Phase 3 (E-esc) | Vinblastine & Prednisone | Did not meet primary endpoint of early progression at week 6 and response at week 12 |
Chemotherapy
- Methotrexate (MTX) 500 mg/m2 IV once per day on days 1, 15, 29
- Vinblastine (Velban) 6 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36
Glucocorticoid therapy
- Prednisone (Sterapred) 40 mg/m2/day PO on days 1 to 28, then tapered off by day 42
6-week course
Subsequent treatment
- See paper for details of treatment beyond induction.
References
- LCH-III: Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. link to original article contains dosing details in manuscript PubMed NCT00276757
Vinblastine & Prednisone
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gadner et al. 2001 (LCH-I) | 1991-1995 | Phase 3 (E-switch-ic) | Etoposide & Prednisone | Did not meet efficacy endpoints |
Gadner et al. 2007 (LCH-II) | 1996-2001 | Phase 3 (C) | Etoposide, Vinblastine, Prednisone | Did not meet primary endpoint of rapid response |
Gadner et al. 2013 (LCH-III) | 2001-2008 | Phase 3 (C) | Methotrexate, Vinblastine, Prednisone | Did not meet primary endpoint of early progression at week 6 and response at week 12 |
Chemotherapy
- Vinblastine (Velban) as follows:
- Cycle 1: 6 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36
- Cycles 2 to 7: 6 mg/m2 IV bolus once on day 1
Glucocorticoid therapy
- Prednisone (Sterapred) as follows:
- Cycle 1: 40 mg/m2/day split three times per day for 4 weeks, then tapering off over 2 weeks
- Cycles 2 to 7: 40 mg/m2/day split three times per day on days 1 to 5
6-week course, then 21-day cycle for 6 cycles
References
- LCH-I: Gadner H, Grois N, Arico M, Broadbent V, Ceci A, Jakobson A, Komp D, Michaelis J, Nicholson S, Pötschger U, Pritchard J, Ladisch S; Histiocyte Society. A randomized trial of treatment for multisystem Langerhans' cell histiocytosis. J Pediatr. 2001 May;138(5):728-34. Erratum in: J Pediatr 2001 Jul;139(1):170. link to original article PubMed
- LCH-II: Gadner H, Grois N, Pötschger U, Minkov M, Aricò M, Braier J, Broadbent V, Donadieu J, Henter JI, McCarter R, Ladisch S; Histiocyte Society. Improved outcome in multisystem Langerhans cell histiocytosis is associated with therapy intensification. Blood. 2008 Mar 1;111(5):2556-62. Epub 2007 Dec 18. link to original article contains dosing details in manuscript PubMed ISRCTN57679341
- LCH-III: Gadner H, Minkov M, Grois N, Pötschger U, Thiem E, Aricò M, Astigarraga I, Braier J, Donadieu J, Henter JI, Janka-Schaub G, McClain KL, Weitzman S, Windebank K, Ladisch S; Histiocyte Society. Therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis. Blood. 2013 Jun 20;121(25):5006-14. Epub 2013 Apr 15. link to original article PubMed NCT00276757
Relapsed or refractory
Cladribine monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Weitzman et al. 2009 (LCH-S-98) | 1999-04 to NR | Phase 2 |
Chemotherapy
- Cladribine (Leustatin) 5 mg/m2 IV over 2 hours once per day on days 1 to 5
21-day cycle for up to 6 cycles
References
- LCH-S-98: Weitzman S, Braier J, Donadieu J, Egeler RM, Grois N, Ladisch S, Pötschger U, Webb D, Whitlock J, Arceci RJ. 2'-Chlorodeoxyadenosine (2-CdA) as salvage therapy for Langerhans cell histiocytosis (LCH): results of the LCH-S-98 protocol of the Histiocyte Society. Pediatr Blood Cancer. 2009 Dec 15;53(7):1271-6. link to original article contains dosing details in manuscript PubMed
Cladribine & Cytarabine
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Donadieu et al. 2015 (LCH-S-2005) | 2005-04 to 2010-11 | Phase 2 |
Chemotherapy
- Cladribine (Leustatin) by the following weight-based criteria:
- 10 kg or more: 9 mg/m2 IV over 2 hours once per day on days 2 to 6, should not be administered simultaneously with cytarabine
- Less than 10 kg: 0.3 mg/kg IV over 2 hours once per day on days 2 to 6, should not be administered simultaneously with cytarabine
- Cytarabine (Ara-C) 500 mg/m2 IV over 2 hours twice per day on days 1 to 5, should not be administered simultaneously with cladribine
35-day cycle for 2 or more cycles
Subsequent treatment
- LCH-S-2005, patients with a good response: Cladribine consolidation
References
- LCH-S-2005: Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. link to original article contains dosing details in manuscript link to PMC article PubMed
Cobimetinib monotherapy
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence |
---|---|---|
Diamond et al. 2019 (MSK 15-216) | 2016-NR | Phase 2, fewer than 20 pts in this arm (RT) |
Note: there were N=2 patients with LCH; it was unclear if they were untreated or previously treated.
References
- MSK 15-216: Diamond EL, Durham BH, Ulaner GA, Drill E, Buthorn J, Ki M, Bitner L, Cho H, Young RJ, Francis JH, Rampal R, Lacouture M, Brody LA, Ozkaya N, Dogan A, Rosen N, Iasonos A, Abdel-Wahab O, Hyman DM. Efficacy of MEK inhibition in patients with histiocytic neoplasms. Nature. 2019 Mar;567(7749):521-524. Epub 2019 Mar 13. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02649972
Vemurafenib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Hyman et al. 2015 (VE-BASKET) | 2012-2014 | Phase 2, fewer than 20 pts in this arm |
Note: This was part of a basket trial, all patients had BRAF p.V600E mutations. A minority (7/18, 39%) of participants were untreated.
References
- VE-BASKET: Hyman DM, Puzanov I, Subbiah V, Faris JE, Chau I, Blay JY, Wolf J, Raje NS, Diamond EL, Hollebecque A, Gervais R, Elez-Fernandez ME, Italiano A, Hofheinz RD, Hidalgo M, Chan E, Schuler M, Lasserre SF, Makrutzki M, Sirzen F, Veronese ML, Tabernero J, Baselga J. Vemurafenib in multiple nonmelanoma cancers with BRAF V600 mutations. N Engl J Med. 2015 Aug 20;373(8):726-736. link to original article contains dosing details in manuscript link to PMC article PubMed
Relapsed or refractory, consolidation
Cladribine monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Donadieu et al. 2015 (LCH-S-2005) | 2005-04 to 2010-11 | Phase 2 |
Preceding treatment
- Salvage Cladribine & Cytarabine
Chemotherapy
- Cladribine (Leustatin) 5 mg/m2 IV once per day on days 1 to 3
21-day cycle for 2 cycles
Subsequent treatment
- 4-drug maintenance
References
- LCH-S-2005: Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. link to original article contains dosing details in manuscript link to PMC article PubMed
Relapsed or refractory, maintenance
Mercaptopurine, Methotrexate, Vinblastine, Prednisolone
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Donadieu et al. 2015 (LCH-S-2005) | 2005-04 to 2010-11 | Phase 2 |
Preceding treatment
- Salvage Cladribine x 2
Chemotherapy
- Mercaptopurine (6-MP) 50 mg/m2 PO once per day on days 1 to 14
- Methotrexate (MTX) 20 mg/m2 PO once per day on days 1 & 8
- Vinblastine (Velban) as follows:
- Cycles 1 to 13: 6 mg/m2 IV once on day 1
Glucocorticoid therapy
- Prednisolone (Millipred) as follows:
- Cycles 1 to 13: 40 mg/m2 PO once per day on days 1 to 5
14-day cycle for 39 cycles (18 months)
References
- LCH-S-2005: Donadieu J, Bernard F, van Noesel M, Barkaoui M, Bardet O, Mura R, Arico M, Piguet C, Gandemer V, Armari Alla C, Clausen N, Jeziorski E, Lambilliote A, Weitzman S, Henter JI, Van Den Bos C; Salvage Group of the Histiocyte Society. Cladribine and cytarabine in refractory multisystem Langerhans cell histiocytosis: results of an international phase 2 study. Blood. 2015 Sep 17;126(12):1415-23. Epub 2015 Jul 20. link to original article contains dosing details in manuscript link to PMC article PubMed