Difference between revisions of "High-grade B-cell lymphoma"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
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{{#lst:Editorial board transclusions|anhl}}
 
<big>'''Note: High-grade B-cell lymphoma (HGBL) was not considered as a named entity until the 2016 revision of the WHO guidelines, and includes entities such as double-hit lymphoma and triple-hit lymphoma which were previously classified under [[diffuse large B-cell lymphoma]]. We will populate this page with relevant regimens over time.'''</big>
 
<big>'''Note: High-grade B-cell lymphoma (HGBL) was not considered as a named entity until the 2016 revision of the WHO guidelines, and includes entities such as double-hit lymphoma and triple-hit lymphoma which were previously classified under [[diffuse large B-cell lymphoma]]. We will populate this page with relevant regimens over time.'''</big>
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
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|}  
 
|}  
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
 +
=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.'''
 +
==NCCN==
 +
*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1480 NCCN Guidelines - B-cell Lymphomas].''
 +
=Untreated=
 +
==Pola-R-CHP {{#subobject:ugj1b2|Regimen=1}}==
 +
Pola-R-CHP: '''<u>Pola</u>'''tuzumab, '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>P</u>'''rednisone
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:e3jh13|Variant=1}}===
 +
{| 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]]
 +
|-
 +
|[https://doi.org/10.1056/nejmoa2115304 Tilly et al. 2021 (POLARIX)]
 +
|2017-2019
 +
| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
 +
|[[#R-CHOP|R-CHOP]]
 +
| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>PFS24: 76.7% vs 70.2%<br>(HR 0.73, 95% CI 0.57-0.95)
 +
|-
 +
|}
 +
''Note: 26 patients in the experimental arm had double- or triple-hit lymphoma.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Antibody-drug conjugate therapy====
 +
*[[Polatuzumab vedotin (Polivy)]] as follows:
 +
**Cycles 1 to 6: 1.8 mg/kg IV once on day 1
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]] as follows:
 +
**Cycles 1 to 6: 750 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin (Adriamycin)]] as follows:
 +
**Cycles 1 to 6: 50 mg/m<sup>2</sup> IV once on day 1
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] as follows:
 +
**Cycles 1 to 6: 100 mg PO once per day on days 1 to 5
 +
'''21-day cycle for 8 cycles'''
 +
</div></div>
 +
===References===
 +
#'''POLARIX:''' Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, Herbaux C, Burke JM, Matasar M, Rai S, Izutsu K, Mehta-Shah N, Oberic L, Chauchet A, Jurczak W, Song Y, Greil R, Mykhalska L, Bergua-Burgués JM, Cheung MC, Pinto A, Shin HJ, Hapgood G, Munhoz E, Abrisqueta P, Gau JP, Hirata J, Jiang Y, Yan M, Lee C, Flowers CR, Salles G. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Jan 27;386(4):351-363. Epub 2021 Dec 14. [https://doi.org/10.1056/nejmoa2115304 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34904799/ PubMed] [https://clinicaltrials.gov/study/NCT03274492 NCT03274492]
 +
 +
==R-CHOP {{#subobject:240cc2|Regimen=1}}==
 +
R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:e3dfg1|Variant=1}}===
 +
{| 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]]
 +
|-
 +
|[https://doi.org/10.1056/nejmoa2115304 Tilly et al. 2021 (POLARIX)]
 +
|2017-2019
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Pola-R-CHP|Pola-R-CHP]]
 +
| style="background-color:#d73027" |Inferior PFS
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Targeted therapy====
 +
*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]] as follows:
 +
**Cycles 1 to 6: 750 mg/m<sup>2</sup> IV once on day 1
 +
*[[Doxorubicin (Adriamycin)]] as follows:
 +
**Cycles 1 to 6: 50 mg/m<sup>2</sup> IV once on day 1
 +
*[[Vincristine (Oncovin)]] as follows:
 +
**Cycles 1 to 6: 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
 +
====Glucocorticoid therapy====
 +
*[[Prednisone (Sterapred)]] as follows:
 +
**Cycles 1 to 6: 100 mg PO once per day on days 1 to 5
 +
'''21-day cycle for 8 cycles'''
 +
</div></div>
 +
===References===
 +
#'''POLARIX:''' Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, Herbaux C, Burke JM, Matasar M, Rai S, Izutsu K, Mehta-Shah N, Oberic L, Chauchet A, Jurczak W, Song Y, Greil R, Mykhalska L, Bergua-Burgués JM, Cheung MC, Pinto A, Shin HJ, Hapgood G, Munhoz E, Abrisqueta P, Gau JP, Hirata J, Jiang Y, Yan M, Lee C, Flowers CR, Salles G. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Jan 27;386(4):351-363. Epub 2021 Dec 14. [https://doi.org/10.1056/nejmoa2115304 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34904799/ PubMed] [https://clinicaltrials.gov/study/NCT03274492 NCT03274492]
 
=Relapsed or refractory, subsequent lines of therapy=
 
=Relapsed or refractory, subsequent lines of therapy=
 +
==Axicabtagene ciloleucel monotherapy {{#subobject:78231d|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:e3e516|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 +
!style="width: 25%"|Study
 +
!style="width: 25%"|Dates of enrollment
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ Locke et al. 2017 (ZUMA-1)]
 +
|2015-2016
 +
| style="background-color:#ffffbe" |Phase 1/2 (RT), fewer than 20 patients in this subgroup
 +
|ORR: 83%; CR: 59%
 +
Median OS: not reached
 +
Median PFS: 6 months
 +
Median duration of response: 11 months
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Lymphodepletion with [[Autologous_HSCT#Cyclophosphamide_.26_Fludarabine_.28FC.29|FC]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Axicabtagene ciloleucel (Yescarta)]] target dose of 2 × 10<sup>6</sup> CAR T cells/kg IV once on day 0
 +
====Supportive therapy====
 +
*[[Acetaminophen (Tylenol)]] 650 mg PO once on day 0, approximately 60 minutes prior to axi-cel
 +
*[[Diphenhydramine (Benadryl)]] 12.5 mg IV or PO once on day 0, approximately 60 minutes prior to axi-cel
 +
 +
'''One course; patients with initial response and disease progression at least 3 months later could be retreated'''
 +
</div></div>
 +
===References===
 +
#'''ZUMA-1:''' Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. [https://doi.org/10.1016/j.ymthe.2016.10.020 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363293/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28129122/ PubMed] [https://clinicaltrials.gov/study/NCT02348216 NCT02348216]
 +
##'''Update:''' Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. [https://doi.org/10.1056/NEJMoa1707447 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882485/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29226797/ PubMed]
 +
##'''Update:''' Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. [https://doi.org/10.1016/S1470-2045(18)30864-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733402/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30518502/ PubMed]
 +
##'''Update:''' Neelapu SS, Jacobson CA, Ghobadi A, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy AH, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Bot AA, Shen RR, Dong J, Singh K, Miao H, Kim JJ, Zheng Y, Locke FL. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023 May 11;141(19):2307-2315. [https://doi.org/10.1182/blood.2022018893 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36821768/ PubMed]
 +
 +
==Epcoritamab monotherapy {{#subobject:1hc22b|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:7agddc|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/10.1016/s0140-6736(21)00889-8 Hutchings et al. 2021 (EPCORE NHL-1)]
 +
|2020-06-19 to 2022-01-31
 +
| style="background-color:#ffffbe" |Phase 1/2 (RT), fewer than 20 patients in this subgroup
 +
|-
 +
|}
 +
''Note: dates of enrollment are based on the dose-expansion cohort.''
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Epcoritamab (Epkinly)]] as follows:
 +
**Cycle 1: 0.16 mg SC once on day 1, then 0.8 mg SC once on day 8, then 48 mg SC once per day on days 15 & 22
 +
**Cycles 2 & 3: 48 mg SC once per day on days 1, 8, 15, 22
 +
**Cycles 4 to 9: 48 mg SC once per day on days 1 & 15
 +
**Cycle 10 onwards: 48 mg SC once on day 1
 +
====Supportive therapy====
 +
*[[Prednisolone (Millipred)]] as follows:
 +
**Cycle 1: 100 mg PO or IV once per day on days 1 to 4, 8 to 11, 15 to 18, 22 to 25, given 30 to 120 minutes prior to epcoritamab on treatment days 1, 8, 15, 22
 +
*[[Diphenhydramine (Benadryl)]] as follows:
 +
**Cycle 1: 50 mg PO or IV once per day on days 1, 8, 15, 22
 +
*[[Acetaminophen (Tylenol)]] as follows:
 +
**Cycle 1: 650 to 1000 mg PO once per day on days 1, 8, 15, 22
 +
'''28-day cycles'''
 +
</div></div>
 +
===References===
 +
#'''EPCORE NHL-1:''' Hutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, Lewis DJ, Sureda Balari A, Cunningham D, Oliveri RS, Elliott B, DeMarco D, Azaryan A, Chiu C, Li T, Chen KM, Ahmadi T, Lugtenburg PJ. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021 Sep 25;398(10306):1157-1169. Epub 2021 Sep 8. [https://doi.org/10.1016/s0140-6736(21)00889-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34508654/ PubMed] [https://clinicaltrials.gov/study/NCT03625037 NCT03625037]
 +
##'''Update:''' Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Do YR, Feldman T, Gasiorowski R, Jurczak W, Kim TM, Lewis DJ, van der Poel M, Poon ML, Cota Stirner M, Kilavuz N, Chiu C, Chen M, Sacchi M, Elliott B, Ahmadi T, Hutchings M, Lugtenburg PJ. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023 Apr 20;41(12):2238-2247. Epub 2022 Dec 22. [https://doi.org/10.1200/jco.22.01725 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc10115554/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/36548927/ PubMed]
 +
 +
==Lisocabtagene maraleucel monotherapy {{#subobject:6e6u14|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:6nvha6|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/10.1016/s0140-6736(20)31366-0 Abramson et al. 2020 (TRANSCEND NHL-001)]
 +
|2016-01-11 to 2019-07-05
 +
| style="background-color:#91cf61" |Phase 1 (RT)
 +
|-
 +
|}
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Lisocabtagene maraleucel (Breyanzi)]] target dose of 100 x 10<sup>6</sup> CAR T cells IV once on day 0
 +
'''One course'''
 +
</div></div>
 +
===References===
 +
#'''TRANSCEND NHL-001:''' Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1. [https://doi.org/10.1016/s0140-6736(20)31366-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32888407/ PubMed] [https://clinicaltrials.gov/study/NCT02631044 NCT02631044]
 +
##'''Update:''' Abramson JS, Palomba ML, Gordon LI, Lunning M, Wang M, Arnason J, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Dehner C, Kim Y, Ogasawara K, Kostic A, Siddiqi T. Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2024 Feb 1;143(5):404-416. [https://doi.org/10.1182/blood.2023020854 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37890149/ PubMed]
 +
 
==Loncastuximab tesirine monotherapy {{#subobject:jgua99|Regimen=1}}==
 
==Loncastuximab tesirine monotherapy {{#subobject:jgua99|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
Line 33: Line 208:
 
*[[Loncastuximab tesirine (Zynlonta)]] as follows:
 
*[[Loncastuximab tesirine (Zynlonta)]] as follows:
 
**Cycles 1 & 2: 0.15 mg/kg IV over 30 minutes once on day 1
 
**Cycles 1 & 2: 0.15 mg/kg IV over 30 minutes once on day 1
−
**Cycle 3 onwards: 0.075 mg/kg IV over 30 minutes once on day 1
+
**Cycles 3 to 18: 0.075 mg/kg IV over 30 minutes once on day 1
 
====Supportive therapy====
 
====Supportive therapy====
 
*[[Dexamethasone (Decadron)]] 4 mg IV or PO twice per day on days -1 to 2 (3 days total)
 
*[[Dexamethasone (Decadron)]] 4 mg IV or PO twice per day on days -1 to 2 (3 days total)
−
'''21-day cycles for up to 18 cycles (1 year)'''
+
'''21-day cycle for up to 18 cycles (1 year)'''
 +
</div></div>
 +
 
 +
===References===
 +
#'''LOTIS-2:''' Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. Epub 2021 May 11. [https://doi.org/10.1016/s1470-2045(21)00139-x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33989558/ PubMed] [https://clinicaltrials.gov/study/NCT03589469 NCT03589469]
 +
 
 +
==Tisagenlecleucel monotherapy {{#subobject:d68f14|Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:60fc19|Variant=1}}===
 +
{| class="wikitable" style="color:white; background-color:#404040"
 +
|<small>'''FDA-recommended dose'''</small>
 +
|-
 +
|}
 +
{| class="wikitable sortable" style="width: 80%; text-align:center;"
 +
! style="width: 25%" |Study
 +
! style="width: 25%" |Dates of enrollment
 +
! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 +
! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1804980 Schuster et al. 2018 (JULIET)]
 +
|2015-2017
 +
| style="background-color:#ffffbe" |Phase 2 (RT), fewer than 20 patients in this subgroup
 +
| style="background-color:#9ebcda" |ORR: 59% (95% CI, 44-72)
 +
|-
 +
|}
 +
''Note: The FDA-recommended range is 0.6 to 6 x 10<sup>8</sup> CTL019 transduced viable T-cells.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 +
====Preceding treatment====
 +
*Lymphodepletion with [[Autologous_HSCT#Cyclophosphamide_.26_Fludarabine_.28FC.29|FC]] or [[Autologous_HSCT#Bendamustine_monotherapy|Bendamustine]]
 +
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Immunotherapy====
 +
*[[Tisagenlecleucel (Kymriah)]] 1 to 5 x 10<sup>8</sup> CTL019 transduced viable T-cells IV once on day 0
 +
'''One course'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
#'''LOTIS-2:''' Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. Epub 2021 May 11. [https://doi.org/10.1016/s1470-2045(21)00139-x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33989558/ PubMed] NCT03589469
+
<!-- # '''Abstract:''' Schuster SJ, Bishop MR, Tam C, et al. Global Pivotal Phase 2 Trial of the CD19-Targeted Therapy CTL019 in Adult Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)—an Interim Analysis. Hematological Oncology. 2017;35(S2):27. [https://doi.org/10.1002/hon.2437_6 link to abstract] -->
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#'''JULIET:''' Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1. [https://doi.org/10.1056/NEJMoa1804980 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/30501490/ PubMed] [https://clinicaltrials.gov/study/NCT02445248 NCT02445248]
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##'''Update:''' Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. Epub 2021 Sep 10. [https://doi.org/10.1016/s1470-2045(21)00375-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34516954/ PubMed]
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[[Category:High-grade B-cell lymphoma regimens]]
 
[[Category:High-grade B-cell lymphoma regimens]]
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
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[[Category:Aggressive lymphomas]]
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[[Category:Aggressive non-Hodgkin lymphomas]]
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[[Category:Non-Hodgkin lymphomas]]
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[[Category:B-cell lymphomas]]

Revision as of 18:26, 17 May 2024

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Section editor
TarsheenSethi.jpg
 Tarsheen Sethi, MD, MSCI
Yale University
New Haven, CT, USA
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Note: High-grade B-cell lymphoma (HGBL) was not considered as a named entity until the 2016 revision of the WHO guidelines, and includes entities such as double-hit lymphoma and triple-hit lymphoma which were previously classified under diffuse large B-cell lymphoma. We will populate this page with relevant regimens over time.

7 regimens on this page
7 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.

NCCN

Untreated

Pola-R-CHP

Pola-R-CHP: Polatuzumab, Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Tilly et al. 2021 (POLARIX) 2017-2019 Phase 3 (E-RT-switch-ooc) R-CHOP Superior PFS (primary endpoint)
PFS24: 76.7% vs 70.2%
(HR 0.73, 95% CI 0.57-0.95)

Note: 26 patients in the experimental arm had double- or triple-hit lymphoma.

Antibody-drug conjugate therapy

Targeted therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for 8 cycles

References

  1. POLARIX: Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, Herbaux C, Burke JM, Matasar M, Rai S, Izutsu K, Mehta-Shah N, Oberic L, Chauchet A, Jurczak W, Song Y, Greil R, Mykhalska L, Bergua-Burgués JM, Cheung MC, Pinto A, Shin HJ, Hapgood G, Munhoz E, Abrisqueta P, Gau JP, Hirata J, Jiang Y, Yan M, Lee C, Flowers CR, Salles G. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Jan 27;386(4):351-363. Epub 2021 Dec 14. link to original article contains dosing details in manuscript PubMed NCT03274492

R-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Tilly et al. 2021 (POLARIX) 2017-2019 Phase 3 (C) Pola-R-CHP Inferior PFS

Targeted therapy

Chemotherapy

Glucocorticoid therapy

21-day cycle for 8 cycles

References

  1. POLARIX: Tilly H, Morschhauser F, Sehn LH, Friedberg JW, Trněný M, Sharman JP, Herbaux C, Burke JM, Matasar M, Rai S, Izutsu K, Mehta-Shah N, Oberic L, Chauchet A, Jurczak W, Song Y, Greil R, Mykhalska L, Bergua-Burgués JM, Cheung MC, Pinto A, Shin HJ, Hapgood G, Munhoz E, Abrisqueta P, Gau JP, Hirata J, Jiang Y, Yan M, Lee C, Flowers CR, Salles G. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022 Jan 27;386(4):351-363. Epub 2021 Dec 14. link to original article contains dosing details in manuscript PubMed NCT03274492

Relapsed or refractory, subsequent lines of therapy

Axicabtagene ciloleucel monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Efficacy
Locke et al. 2017 (ZUMA-1) 2015-2016 Phase 1/2 (RT), fewer than 20 patients in this subgroup ORR: 83%; CR: 59%

Median OS: not reached Median PFS: 6 months Median duration of response: 11 months

Preceding treatment

  • Lymphodepletion with FC

Immunotherapy

Supportive therapy

One course; patients with initial response and disease progression at least 3 months later could be retreated

References

  1. ZUMA-1: Locke FL, Neelapu SS, Bartlett NL, Siddiqi T, Chavez JC, Hosing CM, Ghobadi A, Budde LE, Bot A, Rossi JM, Jiang Y, Xue AX, Elias M, Aycock J, Wiezorek J, Go WY. Phase 1 results of ZUMA-1: A multicenter study of KTE-C19 anti-CD19 CAR T cell therapy in refractory aggressive lymphoma. Mol Ther. 2017 Jan 4;25(1):285-295. Epub 2017 Jan 4. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02348216
    1. Update: Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, Braunschweig I, Oluwole OO, Siddiqi T, Lin Y, Timmerman JM, Stiff PJ, Friedberg JW, Flinn IW, Goy A, Hill BT, Smith MR, Deol A, Farooq U, McSweeney P, Munoz J, Avivi I, Castro JE, Westin JR, Chavez JC, Ghobadi A, Komanduri KV, Levy R, Jacobsen ED, Witzig TE, Reagan P, Bot A, Rossi J, Navale L, Jiang Y, Aycock J, Elias M, Chang D, Wiezorek J, Go WY. Axicabtagene ciloleucel CAR T-cell therapy in refractory large B-cell lymphoma. N Engl J Med. 2017 Dec 28;377(26):2531-2544. Epub 2017 Dec 10. link to original article contains dosing details in manuscript link to PMC article PubMed
    2. Update: Locke FL, Ghobadi A, Jacobson CA, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy A, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Wiezorek JS, Navale L, Xue A, Jiang Y, Bot A, Rossi JM, Kim JJ, Go WY, Neelapu SS. Long-term safety and activity of axicabtagene ciloleucel in refractory large B-cell lymphoma (ZUMA-1): a single-arm, multicentre, phase 1-2 trial. Lancet Oncol. 2019 Jan;20(1):31-42. Epub 2018 Dec 2. link to original article link to PMC article contains dosing details in manuscript PubMed
    3. Update: Neelapu SS, Jacobson CA, Ghobadi A, Miklos DB, Lekakis LJ, Oluwole OO, Lin Y, Braunschweig I, Hill BT, Timmerman JM, Deol A, Reagan PM, Stiff P, Flinn IW, Farooq U, Goy AH, McSweeney PA, Munoz J, Siddiqi T, Chavez JC, Herrera AF, Bartlett NL, Bot AA, Shen RR, Dong J, Singh K, Miao H, Kim JJ, Zheng Y, Locke FL. Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma. Blood. 2023 May 11;141(19):2307-2315. link to original article PubMed

Epcoritamab monotherapy

Regimen

Study Dates of enrollment Evidence
Hutchings et al. 2021 (EPCORE NHL-1) 2020-06-19 to 2022-01-31 Phase 1/2 (RT), fewer than 20 patients in this subgroup

Note: dates of enrollment are based on the dose-expansion cohort.

Immunotherapy

  • Epcoritamab (Epkinly) as follows:
    • Cycle 1: 0.16 mg SC once on day 1, then 0.8 mg SC once on day 8, then 48 mg SC once per day on days 15 & 22
    • Cycles 2 & 3: 48 mg SC once per day on days 1, 8, 15, 22
    • Cycles 4 to 9: 48 mg SC once per day on days 1 & 15
    • Cycle 10 onwards: 48 mg SC once on day 1

Supportive therapy

  • Prednisolone (Millipred) as follows:
    • Cycle 1: 100 mg PO or IV once per day on days 1 to 4, 8 to 11, 15 to 18, 22 to 25, given 30 to 120 minutes prior to epcoritamab on treatment days 1, 8, 15, 22
  • Diphenhydramine (Benadryl) as follows:
    • Cycle 1: 50 mg PO or IV once per day on days 1, 8, 15, 22
  • Acetaminophen (Tylenol) as follows:
    • Cycle 1: 650 to 1000 mg PO once per day on days 1, 8, 15, 22

28-day cycles

References

  1. EPCORE NHL-1: Hutchings M, Mous R, Clausen MR, Johnson P, Linton KM, Chamuleau MED, Lewis DJ, Sureda Balari A, Cunningham D, Oliveri RS, Elliott B, DeMarco D, Azaryan A, Chiu C, Li T, Chen KM, Ahmadi T, Lugtenburg PJ. Dose escalation of subcutaneous epcoritamab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an open-label, phase 1/2 study. Lancet. 2021 Sep 25;398(10306):1157-1169. Epub 2021 Sep 8. link to original article PubMed NCT03625037
    1. Update: Thieblemont C, Phillips T, Ghesquieres H, Cheah CY, Clausen MR, Cunningham D, Do YR, Feldman T, Gasiorowski R, Jurczak W, Kim TM, Lewis DJ, van der Poel M, Poon ML, Cota Stirner M, Kilavuz N, Chiu C, Chen M, Sacchi M, Elliott B, Ahmadi T, Hutchings M, Lugtenburg PJ. Epcoritamab, a Novel, Subcutaneous CD3xCD20 Bispecific T-Cell-Engaging Antibody, in Relapsed or Refractory Large B-Cell Lymphoma: Dose Expansion in a Phase I/II Trial. J Clin Oncol. 2023 Apr 20;41(12):2238-2247. Epub 2022 Dec 22. link to original article link to PMC article contains dosing details in manuscript PubMed

Lisocabtagene maraleucel monotherapy

Regimen

Study Dates of enrollment Evidence
Abramson et al. 2020 (TRANSCEND NHL-001) 2016-01-11 to 2019-07-05 Phase 1 (RT)

Immunotherapy

One course

References

  1. TRANSCEND NHL-001: Abramson JS, Palomba ML, Gordon LI, Lunning MA, Wang M, Arnason J, Mehta A, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Albertson TM, Garcia J, Kostic A, Mallaney M, Ogasawara K, Newhall K, Kim Y, Li D, Siddiqi T. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020 Sep 19;396(10254):839-852. Epub 2020 Sep 1. link to original article contains dosing details in abstract PubMed NCT02631044
    1. Update: Abramson JS, Palomba ML, Gordon LI, Lunning M, Wang M, Arnason J, Purev E, Maloney DG, Andreadis C, Sehgal A, Solomon SR, Ghosh N, Dehner C, Kim Y, Ogasawara K, Kostic A, Siddiqi T. Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2024 Feb 1;143(5):404-416. link to original article PubMed

Loncastuximab tesirine monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence
Caimi et al. 2021 (LOTIS-2) 2018-2019 Phase 2 (RT)

Antibody-drug conjugate therapy

Supportive therapy

21-day cycle for up to 18 cycles (1 year)

References

  1. LOTIS-2: Caimi PF, Ai W, Alderuccio JP, Ardeshna KM, Hamadani M, Hess B, Kahl BS, Radford J, Solh M, Stathis A, Zinzani PL, Havenith K, Feingold J, He S, Qin Y, Ungar D, Zhang X, Carlo-Stella C. Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800. Epub 2021 May 11. link to original article contains dosing details in abstract PubMed NCT03589469

Tisagenlecleucel monotherapy

Regimen

FDA-recommended dose
Study Dates of enrollment Evidence Efficacy
Schuster et al. 2018 (JULIET) 2015-2017 Phase 2 (RT), fewer than 20 patients in this subgroup ORR: 59% (95% CI, 44-72)

Note: The FDA-recommended range is 0.6 to 6 x 108 CTL019 transduced viable T-cells.

Preceding treatment

Immunotherapy

One course

References

  1. JULIET: Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, Jäger U, Jaglowski S, Andreadis C, Westin JR, Fleury I, Bachanova V, Foley SR, Ho PJ, Mielke S, Magenau JM, Holte H, Pantano S, Pacaud LB, Awasthi R, Chu J, Anak Ö, Salles G, Maziarz RT; JULIET Investigators. Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2019 Jan 3;380(1):45-56. Epub 2018 Dec 1. link to original article contains dosing details in supplement PubMed NCT02445248
    1. Update: Schuster SJ, Tam CS, Borchmann P, Worel N, McGuirk JP, Holte H, Waller EK, Jaglowski S, Bishop MR, Damon LE, Foley SR, Westin JR, Fleury I, Ho PJ, Mielke S, Teshima T, Janakiram M, Hsu JM, Izutsu K, Kersten MJ, Ghosh M, Wagner-Johnston N, Kato K, Corradini P, Martinez-Prieto M, Han X, Tiwari R, Salles G, Maziarz RT. Long-term clinical outcomes of tisagenlecleucel in patients with relapsed or refractory aggressive B-cell lymphomas (JULIET): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2021 Oct;22(10):1403-1415. Epub 2021 Sep 10. link to original article PubMed
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