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Note: some MZL regimens can be found on dedicated pages:

B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphomas)

Guidelines

ESMO

2020: Zucca et al. Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Older

2013: Dreyling et al. ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma PubMed

NCCN

NCCN Guidelines - B-cell Lymphomas

First-line therapy, randomized data

Bendamustine & Rituximab (BR)

BR: Bendamustine, Rituximab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Flinn et al. 2014 (BRIGHT)	2009-2012	Phase 3 (E-switch-ic)	1. R-CHOP 2. R-CVP	Superior PFS¹

¹Reported efficacy for BRIGHT is based on the 2017 update.

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 1 & 2

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive therapy

Antiemetics, antipyretics, and antibiotics according to local standard of care
Prophylactic use of G-CSF allowed according ASCO guidelines (2006)

28-day cycle for up to 8 cycles (see note)

References

BRIGHT: Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00877006
1. Update: Abstract: Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 link to abstract

Chlorambucil monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Leblond et al. 2012 (WM1)	2001-2009	Phase 3 (E-switch-ic)	Fludarabine	Seems to have inferior OS

Chemotherapy

Chlorambucil (Leukeran) by the following age-based criteria:
- 75 or younger: 8 mg/m² PO once per day on days 1 to 10
- Older than 75: 6 mg/m² PO once per day on days 1 to 10

Supportive therapy

Recommended PCP prophylaxis with ONE of the following:
- Trimethoprim/Sulfamethoxazole (Bactrim SS) 1 tablet PO once per day
- Pentamidine (Nebupent) 300 mg inhaled once per month

28-day cycle for up to 12 cycles

References

WM1: Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. link to original article contains dosing details in manuscript PubMed NCT00566332; NCT00608374

Fludarabine monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Leblond et al. 2012 (WM1)	2001-2009	Phase 3 (E-switch-ic)	Chlorambucil	Seems to have superior OS Median OS: NYR vs 69.5 mo (HR 0.69, 95% CI 0.48-1.00)

Chemotherapy

Fludarabine (Fludara) by the following age-based criteria:
- 75 or younger: 40 mg/m² PO once per day on days 1 to 5
- Older than 75: 30 mg/m² PO once per day on days 1 to 5

Supportive therapy

Recommended PCP prophylaxis with ONE of the following:
- Trimethoprim/Sulfamethoxazole (Bactrim SS) 1 tablet PO once per day
- Pentamidine (Nebupent) 300 mg inhaled once per month
Herpes zoster prophylaxis with ONE of the following:
- Valacyclovir (Valtrex) 500 mg PO once per day
- Acyclovir (Zovirax) 200 to 400 mg PO twice per day

28-day cycle for up to 6 cycles

References

WM1: Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. link to original article contains dosing details in manuscript PubMed NCT00566332; NCT00608374

Ibrutinib monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (MSKCC 19-243)	2019-2024	Phase 3 (C)	Ibrutinib & Rituximab	TBD

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

Targeted therapy

Ibrutinib (Imbruvica) 560 mg PO once per day

Continued indefinitely

References

MSKCC 19-243: NCT04212013

R-CHOP

R-CHOP: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone
R-CHOP-21: Rituximab, Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone every 21 days
CHOP-R: Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin (Vincristine), Prednisone, Rituximab

Example orders

Example orders for R-CHOP in lymphoma

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Flinn et al. 2014 (BRIGHT)	2009-2012	Phase 3, <20 in this arm (C)	1. BR	Seems to have non-inferior CR rate
Flinn et al. 2014 (BRIGHT)	2009-2012	Phase 3, <20 in this arm (C)	2. R-CVP	Not directly compared

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

Chemotherapy

Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
Doxorubicin (Adriamycin) 50 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1

Glucocorticoid therapy

Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive therapy

Antiemetics, antipyretics, and antibiotics per local standard of care
G-CSF "according to the American Society of Clinical Oncology guidelines"

21-day cycle for up to 8 cycles

References

BRIGHT: Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00877006
1. Update: Abstract: Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 link to abstract

R-CVP

R-CVP: Rituximab, Cyclophosphamide, Vincristine, Prednisone

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Flinn et al. 2014 (BRIGHT)	2009-2012	Phase 3, <20 in this arm (C)	1. BR	Seems to have non-inferior CR rate
Flinn et al. 2014 (BRIGHT)	2009-2012	Phase 3, <20 in this arm (C)	2. R-CHOP	Not directly compared

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

Chemotherapy

Cyclophosphamide (Cytoxan) 750 mg/m² or 1000 mg/m² IV once on day 1
Vincristine (Oncovin) 1.4 mg/m² (maximum dose of 2 mg) IV once on day 1

Glucocorticoid therapy

Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5

Supportive therapy

Antiemetics, antipyretics, and antibiotics per local standard of care
G-CSF "according to the American Society of Clinical Oncology guidelines"

21-day cycle for up to 8 cycles

References

BRIGHT: Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00877006

Rituximab monotherapy

Regimen

Study	Years of enrollment	Evidence
Williams et al. 2016 (RESORT substudy)	2003-2008	Non-randomized portion of RCT

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

Supportive therapy

Acetaminophen (Tylenol) 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to Rituximab (Rituxan)
Diphenhydramine (Benadryl) 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to Rituximab (Rituxan)

4-week course

Subsequent treatment

RESORT substudy, patients with PR/CR: Indefinite rituximab versus salvage rituximab at time of progression

References

RESORT substudy: Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. link to original article contains dosing details in abstract link to PMC article PubMed NCT01406782

First-line therapy, non-randomized or retrospective data

Ibritumomab tiuxetan protocol

Regimen

Study	Evidence
Samaniego et al. 2014 (MDACC 2005-0512)	Phase 2, <20 patients reported
Lossos et al. 2014 (SCCC-2005133)	Phase 2, <20 patients reported

Targeted therapy

Rituximab (Rituxan) 250 mg/m² IV once per day on days 1 & 8, given first on day 8

Radioconjugate therapy

Ibritumomab tiuxetan & Yttrium-90 (Zevalin) IV once on day 8, given second, by the following laboratory-based criteria:
- Platelet count at least 150 x 10⁹/L: 14.8 MBq/kg (maximum dose of 1184 MBq)
- Platelet count between 100 and 149 x 10⁹/L: 11.1 MBq/kg (maximum dose of 1184 MBq)

8-day course

References

MDACC 2005-0512: Samaniego F, Berkova Z, Romaguera JE, Fowler N, Fanale MA, Pro B, Shah JJ, McLaughlin P, Sehgal L, Selvaraj V, Braun FK, Mathur R, Feng L, Neelapu SS, Kwak LW. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease. Br J Haematol. 2014 Oct;167(2):207-13. Epub 2014 Jul 8. link to original article contains dosing details in manuscript PubMed NCT00493467
SCCC-2005133: Lossos IS, Fabregas JC, Koru-Sengul T, Miao F, Goodman D, Serafini AN, Hosein PJ, Stefanovic A, Rosenblatt JD, Hoffman JE. Phase II study of (90)Y Ibritumomab tiuxetan (Zevalin) in patients with previously untreated marginal zone lymphoma. Leuk Lymphoma. 2015 Jun;56(6):1750-5. Epub 2014 Nov 20. link to original article PubMed NCT00453102

Lenalidomide & Rituximab (R²)

Regimen

Study	Evidence
Fowler et al. 2014 (MDACC 2008-0042)	Phase 2

Targeted therapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
Rituximab (Rituxan) 375 mg/m² IV once on day 1

28-day cycle for up to 8 to 12 cycles

References

MDACC 2008-0042: Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. Epub 2014 Oct 15. link to original article contains dosing details in abstract link to PMC article PubMed NCT00695786

PCR

PCR: Pentostatin, Cyclophosphamide, Rituximab

Regimen

Study	Evidence
Samaniego et al. 2015 (MDACC 2004-0818)	Phase 2, <20 patients in this subgroup

Chemotherapy

Pentostatin (Nipent) 4 mg/m² IV once on day 1
Cyclophosphamide (Cytoxan) 600 mg/m² IV once on day 1

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

Supportive therapy

Ondansetron (Zofran) 8 mg (route not specified) once on day 1, prior to chemotherapy
Diphenhydramine (Benadryl) 25 mg (route not specified) once on day 1, prior to chemotherapy
500 ml of 5% dextrose/one-half normal saline before and after each Pentostatin (Nipent) dose
Filgrastim (Neupogen) at the discretion of the treating physician
Allopurinol (Zyloprim) as follows:
- Cycle 1: 300 mg PO once per day on days 1 to 15
Trimethoprim-Sulfamethoxazole (Bactrim DS) once per day three days per week during and for 1 month following therapy
Acyclovir (Zovirax) 400 mg PO twice per day during and for 1 month following therapy

21-day cycle for 6 cycles

References

MDACC 2004-0818: Samaniego F, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Berkova Z, Khashab T, Sehgal L, Vega-Vasquez F, Kwak LW. Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas. Br J Haematol. 2015 Jun;169(6):814-23. Epub 2015 Mar 31. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00496873

Consolidation after first-line therapy

Rituximab monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Williams et al. 2016 (RESORT substudy)	2003-2008	Phase 3 (E-esc)	Rituximab salvage	Seems to have superior TTTF

Preceding treatment

Rituximab

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once on day 1

13-week cycles

References

RESORT substudy: Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. link to original article contains dosing details in abstract link to PMC article PubMed NCT01406782

Relapsed or refractory, randomized data

Lenalidomide & Rituximab (R²)

Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Leonard et al. 2019 (AUGMENT)	2014-2017	Phase 3 (E-RT-esc)	Rituximab	Superior PFS Median PFS: 39.4 vs 14.1 mo (HR 0.46, 95% CI 0.34-0.62)
Awaiting publication (InMIND)	2021-ongoing	Phase 3 (C)	R² & Tafasitamb	TBD

Prior treatment criteria

AUGMENT: At least 1 prior chemotherapy, immunotherapy, or chemoimmunotherapy and 2 or more previous doses of rituximab
InMIND: At least 1 prior systemic anti-CD20 therapy

Targeted therapy

Lenalidomide (Revlimid) 20 mg PO once per day on days 1 to 21
Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 5: 375 mg/m² IV once on day 1

28-day cycle for 12 cycles

References

AUGMENT: Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. link to original article contains dosing details in abstract link to PMC article PubMed NCT01938001
InMIND: NCT04680052

Rituximab monotherapy

Regimen variant #1, 4-week course

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Williams et al. 2016 (RESORT substudy)	2003-2008	Phase 3 (C)	Rituximab maintenance	Seems to have inferior TTTF

Preceding treatment

RESORT substudy: Rituximab, with progression

Targeted therapy

Rituximab (Rituxan) 375 mg/m² IV once per day on days 1, 8, 15, 22

28-day course

Regimen variant #2, 8 doses

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Leonard et al. 2019 (AUGMENT)	2014-2017	Phase 3 (C)	Lenalidomide & Rituximab	Inferior PFS

Targeted therapy

Rituximab (Rituxan) as follows:
- Cycle 1: 375 mg/m² IV once per day on days 1, 8, 15, 22
- Cycles 2 to 5: 375 mg/m² IV once on day 1

28-day cycle for 5 cycles

References

RESORT substudy: Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. link to original article contains dosing details in abstract link to PMC article PubMed NCT01406782
AUGMENT: Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. link to original article contains dosing details in abstract link to PMC article PubMed NCT01938001

Relapsed or refractory, non-randomized or retrospective data

Bendamustine monotherapy

Regimen

Study	Evidence
Kahl et al. 2010	Phase 2, <20 patients reported

Chemotherapy

Bendamustine 120 mg/m² IV once per day on days 1 & 2

21-day cycle for 6 to 8 cycles

References

Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer. 2010 Jan 1;116(1):106-14. link to original article contains dosing details in manuscript link to PMC article PubMed

Bendamustine & Rituximab (BR)

BR: Bendamustine, Rituximab

Regimen

Study	Evidence
Rummel et al. 2005	Phase 2, <20 patients in this subgroup

Chemotherapy

Bendamustine 90 mg/m² IV once per day on days 2 & 3

Targeted therapy

Rituximab (Rituxan) as follows:
- One week prior to start of cycle 1: 375 mg/m² IV once
- Cycles 1 to 4: 375 mg/m² IV once on day 1
- 4 weeks after cycle 4: 375 mg/m² IV once

28-day cycle for 4 cycles

References

Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. link to original article contains dosing details in manuscript PubMed

Copanlisib monotherapy

Regimen variant #1, flat dose

FDA-recommended dose

Study	Years of enrollment	Evidence	Efficacy
Dreyling et al. 2017 (CHRONOS-1)	2012-NR	Phase 2 (RT)	ORR: 59% (95% CI, 49-68)

Note: this is the FDA-recommended dose and the dose used for most of the patients enrolled in this trial; however, the 2017 publication only details the weight-based dosing (see below). The 2021 subgroup analysis does describe this dosing.

Targeted therapy

Copanlisib (Aliqopa) 60 mg IV over 60 minutes once per day on days 1, 8, 15

28-day cycles

Regimen variant #2, weight-based

Study	Years of enrollment	Evidence	Efficacy
Dreyling et al. 2017 (CHRONOS-1)	2012-NR	Phase 2 (RT)	ORR: 59% (95% CI, 49-68)

Targeted therapy

Copanlisib (Aliqopa) 0.8 mg/kg IV over 60 minutes once per day on days 1, 8, 15

28-day cycles

References

CHRONOS-1: Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, Verhoef G, Linton K, Thieblemont C, Vitolo U, Hiemeyer F, Giurescu M, Garcia-Vargas J, Gorbatchevsky I, Liu L, Koechert K, Peña C, Neves M, Childs BH, Zinzani PL. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep 1;28(9):2169-2178. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01660451
1. Subgroup analysis: Panayiotidis P, Follows GA, Mollica L, Nagler A, Özcan M, Santoro A, Stevens D, Trevarthen D, Hiemeyer F, Garcia-Vargas J, Childs BH, Zinzani PL, Dreyling M. Efficacy and safety of copanlisib in patients with relapsed or refractory marginal zone lymphoma. Blood Adv. 2021 Feb 9;5(3):823-828. link to original article link to PMC article PubMed

Idelalisib monotherapy

On 3/21/2016 Gilead announced that they were stopping seven clinical trials of idelalisib in patients with CLL, SLL, and iNHL due to excess deaths and increased rates of SAEs. A REMS program has also been announced.

Regimen,

Study	Years of enrollment	Evidence
Gopal et al. 2014 (DELTA)	2011-2012	Phase 2, <20 patients in this subgroup

Targeted therapy

Idelalisib (Zydelig) 150 mg PO twice per day

Continued indefinitely

References

DELTA: Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Jan 22. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01282424
1. Update: Abstract: Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). ASH Annual Meeting 2014, Abstract 1708 link to abstract

Ibrutinib monotherapy

Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence	Efficacy
Noy et al. 2017 (PCYC-1121-CA)	2013-2015	Phase 2 (RT)	ORR: 48% (95% CI, 35-62)

Targeted therapy

Ibrutinib (Imbruvica) 560 mg PO once per day

Continued indefinitely

References

PCYC-1121-CA: Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, Collins GP, Ma S, Coleman M, Peles S, Smith S, Barrientos JC, Smith A, Munneke B, Dimery I, Beaupre DM, Chen R. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017 Apr 20;129(16):2224-2232. Epub 2017 Feb 6. link to original article link to PMC article contains dosing details in abstract PubMed NCT01980628
1. Update: Noy A, de Vos S, Coleman M, Martin P, Flowers CR, Thieblemont C, Morschhauser F, Collins GP, Ma S, Peles S, Smith SD, Barrientos JC, Chong E, Wu S, Cheung LW, Kwei K, Hauns B, Arango-Hisijara I, Chen R. Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis. Blood Adv. 2020 Nov 24;4(22):5773-5784. link to original article link to PMC article PubMed

Ox-P

Ox-P: Oxaliplatin & Prednisone

Regimen

Study	Evidence
Oh et al. 2016 (CISL)	Phase 2

Note: the treatment details state that prednisone was used, but later in the text prednisolone is mentioned. The authors have been contacted for clarification.

Chemotherapy

Oxaliplatin (Eloxatin) 130 mg/m² IV over 2 hours once on day 1

Glucocorticoid therapy

Prednisone (Sterapred) 100 mg PO once per day on days 1 to 5 (see note)

21-day cycle for up to 6 cycles

References

Oh SY, Kim WS, Kim JS, Chae YS, Lee GW, Eom HS, Ryoo HM, Lee S, Kim SJ, Yoon DH, Won JH, Hong J, Park J, Lee SM, Hong JY, Park E, Kim HJ, Yang DH, Kim HJ, Suh C. A phase II study of oxaliplatin and prednisone for patients with relapsed or refractory marginal zone lymphoma: Consortium for Improving Survival of Lymphoma trial. Leuk Lymphoma. 2016;57(6):1406-12. link to original article contains dosing details in manuscript PubMed

Vorinostat monotherapy

Regimen

Study	Evidence
Kirschbaum et al. 2011 (PHII-63)	Phase 2, <20 pts in subgroup

Targeted therapy

Vorinostat (Zolinza) 200 mg PO twice per day on days 1 to 14

21-day cycles

References

PHII-63: Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, Nademanee A, Forman SJ, Gandara D, Newman E. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Mar 20;29(9):1198-203. Epub 2011 Feb 7. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00253630

Zanubrutinib monotherapy

Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence
Tam et al. 2019 (BGB-3111-AU-003)	2014-2018	Phase 1/2 (RT)
Opat et al. 2021 (MAGNOLIA)	2019-2020	Phase 2 (RT)

Targeted therapy

Zanubrutinib (Brukinsa) 160 mg PO twice per day

28-day cycles

References

BGB-3111-AU-003: Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. Epub 2019 Jul 24. link to original article link to PMC article PubMed NCT02343120
1. Update: Phillips T, Chan H, Tam CS, Tedeschi A, Johnston P, Oh SY, Opat S, Eom HS, Allewelt H, Stern JC, Tan Z, Novotny W, Huang J, Trotman J. Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv. 2022 Jun 14;6(11):3472-3479. link to original article link to PMC article PubMed
MAGNOLIA: Opat S, Tedeschi A, Linton K, McKay P, Hu B, Chan H, Jin J, Sobieraj-Teague M, Zinzani PL, Coleman M, Thieblemont C, Browett P, Ke X, Sun M, Marcus R, Portell CA, Ardeshna K, Bijou F, Walker P, Hawkes EA, Mapp S, Ho SJ, Talaulikar D, Zhou KS, Co M, Li X, Zhou W, Cappellini M, Tankersley C, Huang J, Trotman J. The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma. Clin Cancer Res. 2021 Dec 1;27(23):6323-6332. Epub 2021 Sep 15. link to original article contains dosing details in manuscript PubMed NCT03846427

Response criteria

NCI Sponsored International Working Group Criteria (1999)

Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. link to original article PubMed

@@ Line 3: / Line 3: @@
 [[#top|Back to Top]]
 </div>
-{{#lst:Section editor transclusions|gi}}
+{{#lst:Section editor transclusions|inhl}}
-<big>'''Note: these are regimens tested in biomarker-specific populations and includes gastric and gastroesophageal cancers. Please see the [[gastric cancer|main gastric cancer page]] or the [[esophageal cancer|main esophageal cancer page]] for other regimens.'''</big>
+''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Marginal_zone_lymphoma_-_historical|historical regimens page]]. If you still can't find it, please let us know so we can add it!''
 {| class="wikitable" style="float:right; margin-right: 5px;"
 |-
@@ Line 10: / Line 10: @@
 <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 |}
+<big>'''Note: some MZL regimens can be found on dedicated pages:
+*'''[[B-cell lymphoma of mucosa-associated lymphoid tissue|B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphomas)]]
+</big>
 {{TOC limit|limit=3}}
 =Guidelines=
-==CAP/ASCP/ASCO==
+==[http://www.esmo.org/ ESMO]==
-*'''2017:''' Bartley et al. [https://doi.org/10.1200/JCO.2016.69.4836 HER2 testing and clinical decision making in gastroesophageal adenocarcinoma] [https://pubmed.ncbi.nlm.nih.gov/28129524 PubMed]
+*'''2020:''' Zucca et al. [https://doi.org/10.1016/j.annonc.2019.10.010 Marginal zone lymphomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
-=Metastatic or locally advanced disease, first-line=
+===Older===
-==Capecitabine & Cisplatin (CX) {{#subobject:c58325|Regimen=1}}==
+*'''2013:''' Dreyling et al. [https://doi.org/10.1093/annonc/mds643 ESMO Consensus conferences: guidelines on malignant lymphoma. part 2: marginal zone lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma] [https://pubmed.ncbi.nlm.nih.gov/23425945 PubMed]
-CX: '''<u>C</u>'''isplatin & '''<u>X</u>'''eloda (Capecitabine)
+==[https://www.nccn.org/ NCCN]==
-<br>XP: '''<u>X</u>'''eloda (Capecitabine) & '''<u>P</u>'''latinol (Cisplatin)
+*[https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf NCCN Guidelines - B-cell Lymphomas]
+=First-line therapy, randomized data=
+==Bendamustine & Rituximab (BR) {{#subobject:ac973d|Regimen=1}}==
+BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:130681|Variant=1}}===
+===Regimen {{#subobject:7926ac|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 27: / Line 33: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
-|2005-2008
+|2009-2012
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Trastuzumab|CX & Trastuzumab]]
+|1. [[#R-CHOP|R-CHOP]]<br>2. [[#R-CVP|R-CVP]]
-| style="background-color:#d73027" |Inferior OS
+|style="background-color:#1a9850"|Superior PFS<sup>1</sup>
 |-
 |}
-''Patients:100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.''
+''<sup>1</sup>Reported efficacy for BRIGHT is based on the 2017 update.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 1 & 2
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+====Targeted therapy====
-'''21-day cycles'''
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+====Supportive therapy====
+*Antiemetics, antipyretics, and antibiotics according to local standard of care
+*Prophylactic use of [[:Category:Granulocyte colony-stimulating factors|G-CSF]] allowed according [https://doi.org/10.1200/jco.2006.06.4451 ASCO guidelines] (2006)
+'''28-day cycle for up to 8 cycles (see note)'''
 </div></div>
 ===References===
-#'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404
+<!-- # Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
-==Capecitabine & Cisplatin (CX) & Trastuzumab {{#subobject:7cbb79|Regimen=1}}==
+# '''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [https://doi.org/10.1182/blood-2013-11-531327 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24591201 PubMed] NCT00877006
-CX & Trastuzumab: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), Trastuzumab
+## '''Update: Abstract:''' Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7500 link to abstract]
+==Chlorambucil monotherapy {{#subobject:10e826|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 80/1600 {{#subobject:cdee6d|Variant=1}}===
+===Regimen {{#subobject:fae569|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
+!style="width: 20%"|Study
-! style="width: 20%" |Years of enrollment
+!style="width: 20%"|Years 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/10.1200/JCO.2016.71.6852 Shah et al. 2017 (HELOISE)]
+|[https://doi.org/10.1200/jco.2012.44.7920 Leblond et al. 2012 (WM1)]
-|2011-2015
+|2001-2009
-| style="background-color:#1a9851" |Phase 3b (C)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-|[[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Trastuzumab|CX & Trastuzumab]]; high-dose
+|[[#Fludarabine_monotherapy|Fludarabine]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|style="background-color:#fc8d59"|Seems to have inferior OS
 |-
 |}
-''Patients: 79% gastric, 21% GE junction, and all patients had an ECOG of 2''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-Patients had overexpression of HER2 protein by immunohistochemistry AND gene amplification by in-situ hybridization.
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Chlorambucil (Leukeran)]] by the following age-based criteria:
-*[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+**75 or younger: 8 mg/m<sup>2</sup> PO once per day on days 1 to 10
-====Targeted therapy====
+**Older than 75: 6 mg/m<sup>2</sup> PO once per day on days 1 to 10
-*[[Trastuzumab (Herceptin)]] as follows:
+====Supportive therapy====
-**Cycle 1: 8 mg/kg IV once on day 1
+*Recommended PCP prophylaxis with ONE of the following:
-**Cycle 2 onwards: 6 mg/kg IV once on day 1
+**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim SS)]] 1 tablet PO once per day
-'''21-day cycle for up to 6 cycles'''
+**[[Pentamidine (Nebupent)]] 300 mg inhaled once per month
-</div>
+'''28-day cycle for up to 12 cycles'''
-<div class="toccolours" style="background-color:#cbd5e7">
+</div></div>
-====Subsequent treatment====
+===References===
-*Trastuzumab maintenance
+<!-- Presented at the 11th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 15-18, 2011, and at the 53th Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
-</div></div><br>
+# '''WM1:''' Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. [https://doi.org/10.1200/jco.2012.44.7920 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23233721 PubMed] NCT00566332; NCT00608374
+==Fludarabine monotherapy {{#subobject:c6da52|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 80/2000 {{#subobject:27adc6|Variant=1}}===
+===Regimen {{#subobject:5adb13|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
+!style="width: 20%"|Study
-! style="width: 20%" |Years of enrollment
+!style="width: 20%"|Years 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/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)]
+|[https://doi.org/10.1200/jco.2012.44.7920 Leblond et al. 2012 (WM1)]
-|2005-2008
+|2001-2009
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
-|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29|CX]]
+|[[#Chlorambucil_monotherapy|Chlorambucil]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 13.8 vs 11.1 mo<br>(HR 0.74, 95% CI 0.60-0.91)
+|style="background-color:#91cf60"|Seems to have superior OS<br>Median OS: NYR vs 69.5 mo<br>(HR 0.69, 95% CI 0.48-1.00)
 |-
-|[https://doi.org/10.1016/S1470-2045(18)30481-9 Tabernero et al. 2018 (JACOB)]
+|}
-|2013-2016
+<div class="toccolours" style="background-color:#b3e2cd">
-| style="background-color:#1a9851" |Phase 3 (C)
+====Chemotherapy====
-|[[#Capecitabine_.26_Cisplatin_.28CX.29.2C_Pertuzumab.2C_Trastuzumab_88|CX, Pertuzumab, Trastuzumab]]
+*[[Fludarabine (Fludara)]] by the following age-based criteria:
-| style="background-color:#fc8d59" |Seems to have inferior OS<br>Median OS: 14.2 vs 17.5 mo<br>(HR 1.19, 95% CI 1.00-1.41)
+**75 or younger: 40 mg/m<sup>2</sup> PO once per day on days 1 to 5
+**Older than 75: 30 mg/m<sup>2</sup> PO once per day on days 1 to 5
+====Supportive therapy====
+*Recommended PCP prophylaxis with ONE of the following:
+**[[Trimethoprim-Sulfamethoxazole (Bactrim DS)|Trimethoprim/Sulfamethoxazole (Bactrim SS)]] 1 tablet PO once per day
+**[[Pentamidine (Nebupent)]] 300 mg inhaled once per month
+*Herpes zoster prophylaxis with ONE of the following:
+**[[Valacyclovir (Valtrex)]] 500 mg PO once per day
+**[[Acyclovir (Zovirax)]] 200 to 400 mg PO twice per day
+'''28-day cycle for up to 6 cycles'''
+</div></div>
+===References===
+<!-- Presented at the 11th International Conference on Malignant Lymphoma, Lugano, Switzerland, June 15-18, 2011, and at the 53th Annual Meeting of the American Society of Hematology, San Diego, CA, December 10-13, 2011. -->
+#'''WM1:''' Leblond V, Johnson S, Chevret S, Copplestone A, Rule S, Tournilhac O, Seymour JF, Patmore RD, Wright D, Morel P, Dilhuydy MS, Willoughby S, Dartigeas C, Malphettes M, Royer B, Ewings M, Pratt G, Lejeune J, Nguyen-Khac F, Choquet S, Owen RG. Results of a randomized trial of chlorambucil versus fludarabine for patients with untreated waldenstrom macroglobulinemia, marginal zone lymphoma, or lymphoplasmacytic lymphoma. J Clin Oncol. 2013 Jan 20;31(3):301-7. Epub 2012 Dec 10. [https://doi.org/10.1200/jco.2012.44.7920 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23233721 PubMed] NCT00566332; NCT00608374
+==Ibrutinib monotherapy {{#subobject:af8usd|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:15cc69|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|Awaiting publication (MSKCC 19-243)
+|2019-2024
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Ibrutinib_.26_Rituximab|Ibrutinib & Rituximab]]
+| style="background-color:#d3d3d3" |TBD
 |-
 |}
-''ToGA patients: 81% gastric, 19% GE junction. 10% of patients with ECOG of 2.''
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*ToGA: overexpression of HER2 protein by immunohistochemistry OR gene amplification by fluorescence in-situ hybridization.
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 ====Targeted therapy====
-*[[Trastuzumab (Herceptin)]] as follows:
+*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
-**Cycle 1: 8 mg/kg IV once on day 1
+'''Continued indefinitely'''
-**Cycle 2 onwards: 6 mg/kg IV once on day 1
-'''21-day cycles'''
 </div></div>
 ===References===
-#'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404
+#'''MSKCC 19-243:''' NCT04212013
-#'''HELOISE:''' Shah MA, Xu RH, Bang YJ, Hoff PM, Liu T, Herráez-Baranda LA, Xia F, Garg A, Shing M, Tabernero J. HELOISE: Phase IIIb randomized multicenter study comparing standard-of-care and higher-dose trastuzumab regimens combined with chemotherapy as first-line therapy in patients with human epidermal growth factor receptor 2-positive metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol. 2017 Aug 1;35(22):2558-2567. Epub 2017 Jun 2.[https://doi.org/10.1200/JCO.2016.71.6852 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28574779 PubMed] NCT01450696
+==R-CHOP {{#subobject:f6aa15|Regimen=1}}==
-#'''JACOB:''' Tabernero J, Hoff PM, Shen L, Ohtsu A, Shah MA, Cheng K, Song C, Wu H, Eng-Wong J, Kim K, Kang YK. Pertuzumab plus trastuzumab and chemotherapy for HER2-positive metastatic gastric or gastro-oesophageal junction cancer (JACOB): final analysis of a double-blind, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2018 Oct;19(10):1372-1384. Epub 2018 Sep 11. [https://doi.org/10.1016/S1470-2045(18)30481-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30217672 PubMed] NCT01774786
+R-CHOP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone
-==CapeOx {{#subobject:c699c3|Regimen=1}}==
+<br>R-CHOP-21: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone every '''<u>21</u>''' days
-CapeOx: '''<u>Cape</u>'''citabine and '''<u>Ox</u>'''aliplatin
+<br>CHOP-R: '''<u>C</u>'''yclophosphamide, '''<u>H</u>'''ydroxydaunorubicin (Doxorubicin), '''<u>O</u>'''ncovin (Vincristine), '''<u>P</u>'''rednisone, '''<u>R</u>'''ituximab
+===Example orders===
+*[[Example orders for R-CHOP in lymphoma]]
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:d1aac0|Variant=1}}===
+===Regimen {{#subobject:a1629d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
@@ Line 136: / Line 160: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2015.62.6598 Hecht et al. 2015 (LOGiC)]
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
-|2008-2012
+|rowspan=2|2009-2012
-| style="background-color:#1a9851" |Phase 3 (C)
+|rowspan=2 style="background-color:#91cf61"|Phase 3, <20 in this arm (C)
-|[[#CapeOx_.26_Lapatinib_99|CapeOx & Lapatinib]]
+|1. [[#Bendamustine_.26_Rituximab_.28BR.29|BR]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 10.5 vs 12.2 mo<br>(HR 1.10, 95% CI 0.89-1.37)
+|style="background-color:#eeee01"|Seems to have non-inferior CR rate
+|-
+|2. [[#R-CVP|R-CVP]]
+|style="background-color:#d3d3d3"|Not directly compared
 |-
 |}
-''100% adenocarcinoma histology (4% esophagus, 9% gastroesophageal junction, 87% gastric origin). 9% with ECOG PS of 2.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*HER2 positive
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
 ====Chemotherapy====
-*[[Capecitabine (Xeloda)]] 850 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+*[[Cyclophosphamide (Cytoxan)]] 750 mg/m<sup>2</sup> IV once on day 1
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
+*[[Doxorubicin (Adriamycin)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+====Glucocorticoid therapy====
+*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
+====Supportive therapy====
+*Antiemetics, antipyretics, and antibiotics per local standard of care
+*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] "according to the [https://doi.org/10.1200/jco.2000.18.20.3558 American Society of Clinical Oncology guidelines]"
 '''21-day cycle for up to 8 cycles'''
 </div></div>
 ===References===
-#'''LOGiC:''' Hecht JR, Bang YJ, Qin SK, Chung HC, Xu JM, Park JO, Jeziorski K, Shparyk Y, Hoff PM, Sobrero A, Salman P, Li J, Protsenko SA, Wainberg ZA, Buyse M, Afenjar K, Houé V, Garcia A, Kaneko T, Huang Y, Khan-Wasti S, Santillana S, Press MF, Slamon D. Lapatinib in combination with capecitabine plus oxaliplatin in human epidermal growth factor receptor 2-positive advanced or metastatic gastric, esophageal, or gastroesophageal adenocarcinoma: TRIO-013/LOGiC--a randomized phase III trial. J Clin Oncol. 2016 Feb 10;34(5):443-51. Epub 2015 Nov 30. [https://doi.org/10.1200/JCO.2015.62.6598 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26628478 PubMed] NCT00680901
+<!-- # Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
-#'''HERIZON-GEA-01:''' NCT05152147
+# '''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [https://doi.org/10.1182/blood-2013-11-531327 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24591201 PubMed] NCT00877006
-==CapeOx, Pembrolizumab, Trastuzumab {{#subobject:gjg8c3|Regimen=1}}==
+## '''Update: Abstract:''' Ian Flinn, Richard van der Jagt, Julie E. Chang, Peter Wood, Tim E. Hawkins, David MacDonald, Judith Trotman, David Simpson, Kathryn S. Kolibaba, Samar Issa, Doreen M. Hallman, Ling Chen, and John M. Burke. First-line treatment of iNHL or MCL patients with BR or R-CHOP/R-CVP: Results of the BRIGHT 5-year follow-up study. Journal of Clinical Oncology 2017 35:15_suppl, 7500-7500 [https://doi.org/10.1200/JCO.2017.35.15_suppl.7500 link to abstract]
-CapeOx, Pembrolizumab, Trastuzumab: '''<u>Cape</u>'''citabine, '''<u>Ox</u>'''aliplatin, Pembrolizumab, Trastuzumab
+==R-CVP {{#subobject:2ba05b|Regimen=1}}==
+R-CVP: '''<u>R</u>'''ituximab, '''<u>C</u>'''yclophosphamide, '''<u>V</u>'''incristine, '''<u>P</u>'''rednisone
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:gzbcc0|Variant=1}}===
+===Regimen {{#subobject:c0bc77|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
@@ Line 168: / Line 199: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ Janjigian et al. 2021 (KEYNOTE-811)]
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ Flinn et al. 2014 (BRIGHT)]
-|2018-2020
+|rowspan=2|2009-2012
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|rowspan=2 style="background-color:#91cf61"|Phase 3, <20 in this arm (C)
-|1. [[#CapeOx_.26_Trastuzumab|CapeOx & Trastuzumab]]<br>2. [[#Cisplatin_.2C_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]]
+|1. [[#Bendamustine_.26_Rituximab_.28BR.29|BR]]
-| style="background-color:#1a9850" |Superior ORR<sup>1</sup>
+|style="background-color:#eeee01"|Seems to have non-inferior CR rate
+|-
+|2. [[#R-CHOP|R-CHOP]]
+|style="background-color:#d3d3d3"|Not directly compared
+|-
+|}
+<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)]] 750 mg/m<sup>2</sup> or 1000 mg/m<sup>2</sup> IV once on day 1
+*[[Vincristine (Oncovin)]] 1.4 mg/m<sup>2</sup> (maximum dose of 2 mg) IV once on day 1
+====Glucocorticoid therapy====
+*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5
+====Supportive therapy====
+*Antiemetics, antipyretics, and antibiotics per local standard of care
+*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] "according to the [https://doi.org/10.1200/jco.2000.18.20.3558 American Society of Clinical Oncology guidelines]"
+'''21-day cycle for up to 8 cycles'''
+</div></div>
+===References===
+<!-- # '''Abstract:''' Ian Flinn et al. An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in First-Line Treatment of Patients with Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL): The Bright Study. 2012 ASH Annual Meeting abstract 902. [https://ash.confex.com/ash/2012/webprogram/Paper51442.html link to abstract] -->
+# '''BRIGHT:''' Flinn IW, van der Jagt R, Kahl BS, Wood P, Hawkins TE, Macdonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014 May 8;123(19):2944-52. Epub 2014 Mar 3. [https://doi.org/10.1182/blood-2013-11-531327 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4260975/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24591201 PubMed] NCT00877006
+==Rituximab monotherapy {{#subobject:c82d07|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:c20616|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ Williams et al. 2016 (RESORT substudy)]
+|2003-2008
+|style="background-color:#91cf61"|Non-randomized portion of RCT
 |-
 |}
-''<sup>1</sup>This is an interim secondary endpoint; primary endpoints are PFS and OS.''
+<div class="toccolours" style="background-color:#b3e2cd">
-<div class="toccolours" style="background-color:#fdcdac">
+====Targeted therapy====
-====Biomarker eligibility criteria====
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-*HER2 positive
+====Supportive therapy====
+*[[Acetaminophen (Tylenol)]] 650 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
+*[[Diphenhydramine (Benadryl)]] 50 mg PO once per day on days 1, 8, 15, 22; 30 minutes prior to [[Rituximab (Rituxan)]]
+'''4-week course'''
 </div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*RESORT substudy, patients with PR/CR: [[#Rituximab_monotherapy_2|Indefinite rituximab]] versus salvage [[#Rituximab_monotherapy_3|rituximab]] at time of progression
+</div></div>
+===References===
+<!-- Presented in part at the American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL, USA. -->
+# '''RESORT substudy:''' Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. [https://doi.org/10.1111/bjh.14007 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26970533 PubMed] NCT01406782
+=First-line therapy, non-randomized or retrospective data=
+==Ibritumomab tiuxetan protocol {{#subobject:cfb3aa|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:619265|Variant=1}}===
+{| class="wikitable" style="width: 40%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1111/bjh.13021 Samaniego et al. 2014 (MDACC 2005-0512)]
+|style="background-color:#ffffbe"|Phase 2, <20 patients reported
+|-
+|[http://www.tandfonline.com/doi/full/10.3109/10428194.2014.975801 Lossos et al. 2014 (SCCC-2005133)]
+|style="background-color:#ffffbe"|Phase 2, <20 patients reported
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Rituximab (Rituxan)]] 250 mg/m<sup>2</sup> IV once per day on days 1 & 8, '''given first on day 8'''
+====Radioconjugate therapy====
+*[[Ibritumomab tiuxetan (Zevalin)|Ibritumomab tiuxetan & Yttrium-90 (Zevalin) ]] IV once on day 8, '''given second''', by the following laboratory-based criteria:
+**Platelet count at least 150 x 10<sup>9</sup>/L: 14.8 MBq/kg (maximum dose of 1184 MBq)
+**Platelet count between 100 and 149 x 10<sup>9</sup>/L: 11.1 MBq/kg (maximum dose of 1184 MBq)
+'''8-day course'''
+</div></div>
+===References===
+<!-- Study results were presented at 12th International Conference on Malignant Lymphoma Lugano, Switzerland, 2013. -->
+# '''MDACC 2005-0512:''' Samaniego F, Berkova Z, Romaguera JE, Fowler N, Fanale MA, Pro B, Shah JJ, McLaughlin P, Sehgal L, Selvaraj V, Braun FK, Mathur R, Feng L, Neelapu SS, Kwak LW. 90Y-ibritumomab tiuxetan radiotherapy as first-line therapy for early stage low-grade B-cell lymphomas, including bulky disease. Br J Haematol. 2014 Oct;167(2):207-13. Epub 2014 Jul 8. [https://doi.org/10.1111/bjh.13021 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25040450 PubMed] NCT00493467
+# '''SCCC-2005133:''' Lossos IS, Fabregas JC, Koru-Sengul T, Miao F, Goodman D, Serafini AN, Hosein PJ, Stefanovic A, Rosenblatt JD, Hoffman JE. Phase II study of (90)Y Ibritumomab tiuxetan (Zevalin) in patients with previously untreated marginal zone lymphoma. Leuk Lymphoma. 2015 Jun;56(6):1750-5. Epub 2014 Nov 20. [http://www.tandfonline.com/doi/full/10.3109/10428194.2014.975801 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25315074 PubMed] NCT00453102
+==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:c8fa86|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:38dadd|Variant=1}}===
+{| class="wikitable" style="width: 40%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370362/ Fowler et al. 2014 (MDACC 2008-0042)]
+|style="background-color:#91cf61"|Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycle for up to 8 to 12 cycles'''
+</div></div>
+===References===
+<!--
+# '''Abstract:''' N. H. Fowler, P. McLaughlin, F. B. Hagemeister, L. W. Kwak, M. A. Fanale, S. S. Neelapu, L. Fayad, R. Z. Orlowski, M. Wang, F. Samaniego. Complete response rates with lenalidomide plus rituximab for untreated indolent B-cell non-Hodgkin's lymphoma. J Clin Oncol 28:15s, 2010 (suppl; abstr 8036). 2010 ASCO Annual Meeting abstract 8036. [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview==abst_detail_view&confID==74&abstractID==53803 link to abstract]
+# '''Abstract:''' Nathan H Fowler, MD, Sattva S. Neelapu, MD, Fredrick B Hagemeister, MD, Peter McLaughlin, MD, Larry W. Kwak, MD, PhD, Jorge E Romaguera, MD, Michelle A. Fanale, MD, Luis E Fayad, MD, Robert Z. Orlowski, M.D., Ph.D., Michael Wang, M.D., Francesco Turturro, MD, Yasuhiro Oki, MD, Linda Catherine Lacerte, RN and Felipe Samaniego, MD, MPH. Lenalidomide and Rituximab for Untreated Indolent Lymphoma: Final Results of a Phase II Study. 2012 ASH Annual Meeting abstract 901. [http://abstracts.hematologylibrary.org/cgi/content/abstract/120/21/901 link to abstract] -->
+# '''MDACC 2008-0042:''' Fowler NH, Davis RE, Rawal S, Nastoupil L, Hagemeister FB, McLaughlin P, Kwak LW, Romaguera JE, Fanale MA, Fayad LE, Westin JR, Shah J, Orlowski RZ, Wang M, Turturro F, Oki Y, Claret LC, Feng L, Baladandayuthapani V, Muzzafar T, Tsai KY, Samaniego F, Neelapu SS. Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial. Lancet Oncol. 2014 Nov;15(12):1311-8. Epub 2014 Oct 15. [https://doi.org/10.1016/S1470-2045(14)70455-3 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4370362/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25439689 PubMed] NCT00695786
+==PCR {{#subobject:6b1b68|Regimen=1}}==
+PCR: '''<u>P</u>'''entostatin, '''<u>C</u>'''yclophosphamide, '''<u>R</u>'''ituximab
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:90e7f7|Variant=1}}===
+{| class="wikitable" style="width: 40%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ Samaniego et al. 2015 (MDACC 2004-0818)]
+|style="background-color:#ffffbe"|Phase 2, <20 patients in this subgroup
+|-
+|}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+*[[Pentostatin (Nipent)]] 4 mg/m<sup>2</sup> IV once on day 1
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Cyclophosphamide (Cytoxan)]] 600 mg/m<sup>2</sup> IV once on day 1
-====Immunotherapy====
-*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 ====Targeted therapy====
-*[[Trastuzumab (Herceptin)]] as follows:
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
-**Cycle 1: 8 mg/kg IV once on day 1
+====Supportive therapy====
-**Cycle 2 onwards: 6 mg/kg IV once on day 1
+*[[Ondansetron (Zofran)]] 8 mg (route not specified) once on day 1, prior to chemotherapy
-'''21-day cycles'''
+*[[Diphenhydramine (Benadryl)]] 25 mg (route not specified) once on day 1, prior to chemotherapy
+*500 ml of 5% dextrose/one-half normal saline before and after each [[Pentostatin (Nipent)]] dose
+*[[Filgrastim (Neupogen)]] at the discretion of the treating physician
+*[[Allopurinol (Zyloprim)]] as follows:
+**Cycle 1: 300 mg PO once per day on days 1 to 15
+*[[Trimethoprim-Sulfamethoxazole (Bactrim DS)]] once per day three days per week during and for 1 month following therapy
+*[[Acyclovir (Zovirax)]] 400 mg PO twice per day during and for 1 month following therapy
+'''21-day cycle for 6 cycles'''
 </div></div>
 ===References===
-#'''KEYNOTE-811:''' Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. [https://doi.org/10.1038/s41586-021-04161-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34912120/ PubMed] NCT03615326
+# '''MDACC 2004-0818:''' Samaniego F, Hagemeister F, Romaguera JE, Fanale MA, Pro B, McLaughlin P, Rodriguez MA, Neelapu SS, Fayad L, Younes A, Feng L, Berkova Z, Khashab T, Sehgal L, Vega-Vasquez F, Kwak LW. Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas. Br J Haematol. 2015 Jun;169(6):814-23. Epub 2015 Mar 31. [https://doi.org/10.1111/bjh.13367 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5278955/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25828695 PubMed] NCT00496873
-==CapeOx & Trastuzumab {{#subobject:gh6cc3|Regimen=1}}==
+=Consolidation after first-line therapy=
-CapeOx & Trastuzumab: '''<u>Cape</u>'''citabine, '''<u>Ox</u>'''aliplatin, Trastuzumab
+==Rituximab monotherapy {{#subobject:1d6299|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:d1aac0|Variant=1}}===
+===Regimen {{#subobject:d2473c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
@@ Line 205: / Line 345: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ Janjigian et al. 2021 (KEYNOTE-811)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ Williams et al. 2016 (RESORT substudy)]
-|2018-2020
+|2003-2008
-| style="background-color:#1a9851" |Phase 3 (C)
+|style="background-color:#1a9851"|Phase 3 (E-esc)
-|1. [[#CapeOx.2C_Pembrolizumab.2C_Trastuzumab|CapeOx, Pembrolizumab, Trastuzumab]]<br>2. [[#Cisplatin_.2C_Fluorouracil_.28CF.29.2C_Pembrolizumab.2C_Trastuzumab_88|CF, Pembrolizumab, Trastuzumab]]
+|[[#Rituximab_monotherapy_3|Rituximab]] salvage
-| style="background-color:#d73027" |Inferior ORR<sup>1</sup>
+|style="background-color:#91cf60"|Seems to have superior TTTF
 |-
 |}
-''<sup>1</sup>This is an interim secondary endpoint; primary endpoints are PFS and OS.''<br>
+<div class="toccolours" style="background-color:#cbd5e8">
-''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
+====Preceding treatment====
-<div class="toccolours" style="background-color:#fdcdac">
+*[[#Rituximab_monotherapy|Rituximab]]
-====Biomarker eligibility criteria====
-*HER2 positive
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
 ====Targeted therapy====
-*[[Trastuzumab (Herceptin)]] as follows:
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once on day 1
-**Cycle 1: 8 mg/kg IV once on day 1
+'''13-week cycles'''
-**Cycle 2 onwards: 6 mg/kg IV once on day 1
-'''21-day cycles'''
 </div></div>
 ===References===
-#'''KEYNOTE-811:''' Janjigian YY, Kawazoe A, Yañez P, Li N, Lonardi S, Kolesnik O, Barajas O, Bai Y, Shen L, Tang Y, Wyrwicz LS, Xu J, Shitara K, Qin S, Van Cutsem E, Tabernero J, Li L, Shah S, Bhagia P, Chung HC. The KEYNOTE-811 trial of dual PD-1 and HER2 blockade in HER2-positive gastric cancer. Nature. 2021 Dec;600(7890):727-730. Epub 2021 Dec 15. [https://doi.org/10.1038/s41586-021-04161-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8959470/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34912120/ PubMed] NCT03615326
+<!-- Presented in part at the American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL, USA. -->
-==Cisplatin & Fluorouracil (CF) {{#subobject:4d9936|Regimen=1}}==
+# '''RESORT substudy:''' Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. [https://doi.org/10.1111/bjh.14007 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26970533 PubMed] NCT01406782
-CF: '''<u>C</u>'''isplatin & '''<u>F</u>'''luorouracil
+=Relapsed or refractory, randomized data=
-<br>FP: '''<u>F</u>'''luorouracil & '''<u>P</u>'''latinol (Cisplatin)
+==Lenalidomide & Rituximab (R<sup>2</sup>) {{#subobject:00ba12|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:782e95|Variant=1}}===
+===Regimen {{#subobject:44f899|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
+|-
+|}
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
+!style="width: 20%"|Study
-! style="width: 20%" |Years of enrollment
+!style="width: 20%"|Years 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ Leonard et al. 2019 (AUGMENT)]
+|2014-2017
+|style="background-color:#1a9851"|Phase 3 (E-RT-esc)
+|[[#Rituximab_monotherapy_3|Rituximab]]
+|style="background-color:#1a9850"|Superior PFS<br>Median PFS: 39.4 vs 14.1 mo<br>(HR 0.46, 95% CI 0.34-0.62)
 |-
-|[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)]
+|Awaiting publication (InMIND)
-|2005-2008
+|2021-ongoing
 | style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Trastuzumab|CF & Trastuzumab]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Trastuzumab|CX & Trastuzumab]]
+|[[#Lenalidomide.2C_Rituximab.2C_Tafasitamab_66|R<sup>2</sup> & Tafasitamb]]
-| style="background-color:#d73027" |Inferior OS
+| style="background-color:#d3d3d3" |TBD
 |-
 |}
-''ToGA Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.''
 <div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
+====Prior treatment criteria====
-*Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.
+*AUGMENT: At least 1 prior chemotherapy, immunotherapy, or chemoimmunotherapy and 2 or more previous doses of rituximab
+*InMIND: At least 1 prior systemic [[Regimen_classes#Anti-CD20-based_regimen|anti-CD20 therapy]]
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Targeted therapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
+*[[Lenalidomide (Revlimid)]] 20 mg PO once per day on days 1 to 21
-*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
+*[[Rituximab (Rituxan)]] as follows:
-'''21-day cycle for up to 6 cycles'''
+**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycle for 12 cycles'''
 </div></div>
 ===References===
-#'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404
+# '''AUGMENT:''' Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. [https://doi.org/10.1200/JCO.19.00010 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30897038 PubMed] NCT01938001
-==Cisplatin & Fluorouracil (CF) & Trastuzumab {{#subobject:ca9cd1|Regimen=1}}==
+#'''InMIND:''' NCT04680052
-CF & Trastuzumab: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil, Trastuzumab
+==Rituximab monotherapy {{#subobject:29dc8b|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:b2731|Variant=1}}===
+===Regimen variant #1, 4-week course {{#subobject:73277c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 273: / Line 418: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/S0140-6736(10)61121-X Bang et al. 2010 (ToGA)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ Williams et al. 2016 (RESORT substudy)]
-|2005-2008
+|2003-2008
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+|style="background-color:#1a9851"|Phase 3 (C)
-|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29|CX]]
+|[[#Rituximab_monotherapy_2|Rituximab]] maintenance
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 13.8 vs 11.1 mo<br>(HR 0.74, 95% CI 0.60-0.91)
+|style="background-color:#fc8d59"|Seems to have inferior TTTF
 |-
 |}
-''Patients: 100% adenocarcinoma (19% gastroesophageal junction, 81% gastric). 10% with ECOG of 2.''
+<div class="toccolours" style="background-color:#cbd5e8">
-<div class="toccolours" style="background-color:#fdcdac">
+====Preceding treatment====
-====Biomarker eligibility criteria====
+*RESORT substudy: [[#Rituximab_monotherapy|Rituximab]], with progression
-*Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 ====Targeted therapy====
-*[[Trastuzumab (Herceptin)]] as follows:
+*[[Rituximab (Rituxan)]] 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-**Cycle 1: 8 mg/kg IV once on day 1
+'''28-day course'''
-**Cycle 2 onwards: 6 mg/kg IV once on day 1
+</div></div><br>
-'''21-day cycles'''
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 8 doses {{#subobject:44f899|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Years 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://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ Leonard et al. 2019 (AUGMENT)]
+|2014-2017
+|style="background-color:#1a9851"|Phase 3 (C)
+|[[#Lenalidomide_.26_Rituximab_.28R2.29_2|Lenalidomide & Rituximab]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Rituximab (Rituxan)]] as follows:
+**Cycle 1: 375 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+**Cycles 2 to 5: 375 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycle for 5 cycles'''
 </div></div>
 ===References===
-#'''ToGA:''' Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [https://doi.org/10.1016/S0140-6736(10)61121-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20728210 PubMed] NCT01041404
+<!-- Presented in part at the American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL, USA. -->
-#'''HERIZON-GEA-01:''' NCT05152147
+# '''RESORT substudy:''' Williams ME, Hong F, Gascoyne RD, Wagner LI, Krauss JC, Habermann TM, Swinnen LJ, Schuster SJ, Peterson CG, Sborov MD, Martin SE, Weiss M, Ehmann WC, Horning SJ, Kahl BS; Eastern Cooperative Oncology Group. Rituximab extended schedule or retreatment trial for low tumour burden non-follicular indolent B-cell non-Hodgkin lymphomas: Eastern Cooperative Oncology Group Protocol E4402. Br J Haematol. 2016 Jun;173(6):867-75. Epub 2016 Mar 11. [https://doi.org/10.1111/bjh.14007 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4900920/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26970533 PubMed] NCT01406782
-#'''KEYNOTE-811:''' NCT03615326
+# '''AUGMENT:''' Leonard JP, Trneny M, Izutsu K, Fowler NH, Hong X, Zhu J, Zhang H, Offner F, Scheliga A, Nowakowski GS, Pinto A, Re F, Fogliatto LM, Scheinberg P, Flinn IW, Moreira C, Cabeçadas J, Liu D, Kalambakas S, Fustier P, Wu C, Gribben JG; AUGMENT Trial Investigators. AUGMENT: a phase III study of lenalidomide plus rituximab versus placebo plus rituximab in relapsed or refractory indolent lymphoma. J Clin Oncol. 2019 May 10;37(14):1188-1199. Epub 2019 Mar 21. [https://doi.org/10.1200/JCO.19.00010 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7035866/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30897038 PubMed] NCT01938001
-=Metastatic or locally advanced disease, subsequent lines of therapy=
+=Relapsed or refractory, non-randomized or retrospective data=
-==Docetaxel monotherapy {{#subobject:4f3230|Regimen=1}}==
+==Bendamustine monotherapy {{#subobject:ed6258|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:3b47ab|Variant=1}}===
+===Regimen {{#subobject:7c58ab|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 20%" |Study
+!style="width: 25%"|Study
-! style="width: 20%" |Years of enrollment
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! 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/10.1016/S1470-2045(17)30111-0 Thuss-Patience et al. 2017 (GATSBY)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ Kahl et al. 2010]
-|2012-2013
+|style="background-color:#ffffbe"|Phase 2, <20 patients reported
-| style="background-color:#1a9851" |Phase 2/3 (C)
-|[[#Trastuzumab_emtansine_monotherapy_99|T-DM1]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.6 vs 7.9 mo<br>(HR 0.87, 95% CI 0.66-1.15)
 |-
 |}
-''Note: study patients could only have been treated by one other regimen and could not have been exposed to anthracyclines''
-''Patients: 68% gastric, 32% GEJ''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*HER2-positive disease
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
-'''21-day cycles'''
+'''21-day cycle for 6 to 8 cycles'''
 </div></div>
 ===References===
-#'''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://doi.org/10.1016/S1470-2045(17)30111-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28343975 PubMed] NCT01641939
+<!-- Preliminary research findings from this study were presented at the 2007 American Society of Hematology Annual Meeting and Exposition, Atlanta, Georgia, December 8-11, 2007. -->
-==Trastuzumab deruxtecan monotherapy {{#subobject:d2616v|Regimen=1}}==
+# Kahl BS, Bartlett NL, Leonard JP, Chen L, Ganjoo K, Williams ME, Czuczman MS, Robinson KS, Joyce R, van der Jagt RH, Cheson BD. Bendamustine is effective therapy in patients with rituximab-refractory, indolent B-cell non-Hodgkin lymphoma: results from a multicenter study. Cancer. 2010 Jan 1;116(1):106-14. [https://doi.org/10.1002/cncr.24714 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916680/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19890959 PubMed]
+==Bendamustine & Rituximab (BR) {{#subobject:9b8c84|Regimen=1}}==
+BR: '''<u>B</u>'''endamustine, '''<u>R</u>'''ituximab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:577cd6|Variant=1}}===
+===Regimen {{#subobject:c98fa0|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 20%" |Study
+!style="width: 25%"|Study
-! style="width: 20%" |Years of enrollment
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! 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/nejmoa2004413 Shitara et al. 2020 (DESTINY-Gastric01)]
+|[https://doi.org/10.1200/jco.2005.08.100 Rummel et al. 2005]
-|2017-2019
+|style="background-color:#ffffbe"|Phase 2, <20 patients in this subgroup
-| style="background-color:#1a9851" |Randomized Phase 2 (E-RT-switch-ooc)
-|Investigator's choice of:<br> 1. [[#Irinotecan_monotherapy_2|Irinotecan]]<br>2. [[#Paclitaxel_monotherapy|Paclitaxel]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 12.5 vs 8.4 mo<br>(HR 0.59, 95% CI 0.39-0.88)
 |-
 |}
-''Note: the dose is different from the FDA-approved dose for breast cancer.''
-''Patients had received a median of two prior therapies for advanced or metastatic disease (17% had received at least four prior therapies, 72% had previously received ramucirumab and 86% had received taxanes).''
-''The median time since the last administration of trastuzumab was 5.9 months in the trastuzumab deruxtecan group and 6.5 months among those in the investigator's choice group.''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*HER2 over-expression
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Antibody-drug conjugate therapy====
+====Chemotherapy====
-*[[Trastuzumab deruxtecan (Enhertu)]] 6.4 mg/kg IV once on day 1
+*[[Bendamustine]] 90 mg/m<sup>2</sup> IV once per day on days 2 & 3
-'''21-day cycles'''
+====Targeted therapy====
+*[[Rituximab (Rituxan)]] as follows:
+**One week prior to start of cycle 1: 375 mg/m<sup>2</sup> IV once
+**Cycles 1 to 4: 375 mg/m<sup>2</sup> IV once on day 1
+**4 weeks after cycle 4: 375 mg/m<sup>2</sup> IV once
+'''28-day cycle for 4 cycles'''
 </div></div>
 ===References===
-#'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182 PubMed] NCT03329690
+# Rummel MJ, Al-Batran SE, Kim SZ, Welslau M, Hecker R, Kofahl-Krause D, Josten KM, Dürk H, Rost A, Neise M, von Grünhagen U, Chow KU, Hansmann ML, Hoelzer D, Mitrou PS. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin's lymphoma. J Clin Oncol. 2005 May 20;23(15):3383-9. [https://doi.org/10.1200/jco.2005.08.100 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15908650 PubMed]
-==Irinotecan monotherapy {{#subobject:6df2c0|Regimen=1}}==
+==Copanlisib monotherapy {{#subobject:93db44|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:fa1ef9|Variant=1}}===
+===Regimen variant #1, flat dose {{#subobject:13b566|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable" style="color:white; background-color:#404040"
-! style="width: 20%" |Study
+|<small>'''FDA-recommended dose'''</small>
-! style="width: 20%" |Years of enrollment
+|-
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+|}
-! style="width: 20%" |Comparator
+{| class="wikitable" style="width: 80%; text-align:center;"
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 25%"|Study
+!style="width: 25%"|Years 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/PMC5834070/ Dreyling et al. 2017 (CHRONOS-1)]
+|2012-NR
+| style="background-color:#91cf61" |Phase 2 (RT)
+| style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-68)
+|-
+|}
+''Note: this is the FDA-recommended dose and the dose used for most of the patients enrolled in this trial; however, the 2017 publication only details the weight-based dosing (see below). The 2021 subgroup analysis does describe this dosing.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Copanlisib (Aliqopa)]] 60 mg IV over 60 minutes once per day on days 1, 8, 15
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, weight-based {{#subobject:f9baa2|Variant=1}}===
+{| class="wikitable" style="width: 80%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|Years of enrollment
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[https://doi.org/10.1056/nejmoa2004413 Shitara et al. 2020 (DESTINY-Gastric01)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ Dreyling et al. 2017 (CHRONOS-1)]
-|2017-2019
+|2012-NR
-| style="background-color:#1a9851" |Randomized Phase 2 (C)
+| style="background-color:#91cf61" |Phase 2 (RT)
-|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
+| style="background-color:#9ebcda" |ORR: 59% (95% CI, 49-68)
-| style="background-color:#d73027" |Inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*DESTINY-Gastric01: HER2 over-expression
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Targeted therapy====
-*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1
+*[[Copanlisib (Aliqopa)]] 0.8 mg/kg IV over 60 minutes once per day on days 1, 8, 15
-'''14-day cycles'''
+'''28-day cycles'''
 </div></div>
 ===References===
-#'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182 PubMed] NCT03329690
+#'''CHRONOS-1:''' Dreyling M, Morschhauser F, Bouabdallah K, Bron D, Cunningham D, Assouline SE, Verhoef G, Linton K, Thieblemont C, Vitolo U, Hiemeyer F, Giurescu M, Garcia-Vargas J, Gorbatchevsky I, Liu L, Koechert K, Peña C, Neves M, Childs BH, Zinzani PL. Phase II study of copanlisib, a PI3K inhibitor, in relapsed or refractory, indolent or aggressive lymphoma. Ann Oncol. 2017 Sep 1;28(9):2169-2178. [https://academic.oup.com/annonc/article/28/9/2169/3868097 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5834070/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28633365 PubMed] NCT01660451
-==Paclitaxel monotherapy {{#subobject:2dcad9|Regimen=1}}==
+##'''Subgroup analysis:''' Panayiotidis P, Follows GA, Mollica L, Nagler A, Özcan M, Santoro A, Stevens D, Trevarthen D, Hiemeyer F, Garcia-Vargas J, Childs BH, Zinzani PL, Dreyling M. Efficacy and safety of copanlisib in patients with relapsed or refractory marginal zone lymphoma. Blood Adv. 2021 Feb 9;5(3):823-828. [https://doi.org/10.1182/bloodadvances.2020002910 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7876879/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33560394/ PubMed]
+==Idelalisib monotherapy {{#subobject:1c0cad|Regimen=1}}==
+'''On 3/21/2016 Gilead announced that they were stopping seven clinical trials of idelalisib in patients with CLL, SLL, and iNHL due to excess deaths and increased rates of SAEs. A [http://www.zydeligrems.com/ REMS program] has also been announced.'''
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 80 mg/m<sup>2</sup> weekly {{#subobject:0e8f41|Variant=1}}===
+===Regimen, {{#subobject:9da677|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 20%" |Study
+!style="width: 33%"|Study
-! style="width: 20%" |Years of enrollment
+!style="width: 33%"|Years of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/S1470-2045(17)30111-0 Thuss-Patience et al. 2017 (GATSBY)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ Gopal et al. 2014 (DELTA)]
-|2012-2013
+|2011-2012
-| style="background-color:#1a9851" |Phase 2/3 (C)
+|style="background-color:#ffffbe"|Phase 2, <20 patients in this subgroup
-|[[#Trastuzumab_emtansine_monotherapy_99|T-DM1]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.6 vs 7.9 mo<br>(HR 0.87, 95% CI 0.66-1.15)
 |-
 |}
-''GATSBY included patients with GE junction malignancy (68% gastric, 32% GE junction)''
-<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
-*Overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Targeted therapy====
-*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+*[[Idelalisib (Zydelig)]] 150 mg PO twice per day
-'''21-day cycles'''
+'''Continued indefinitely'''
-</div></div><br>
+</div></div>
+===References===
+# '''DELTA:''' Gopal AK, Kahl BS, de Vos S, Wagner-Johnston ND, Schuster SJ, Jurczak WJ, Flinn IW, Flowers CR, Martin P, Viardot A, Blum KA, Goy AH, Davies AJ, Zinzani PL, Dreyling M, Johnson D, Miller LL, Holes L, Li D, Dansey RD, Godfrey WR, Salles GA. PI3Kd inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014 Jan 22. [https://doi.org/10.1056/NEJMoa1314583 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4039496/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24450858 PubMed] NCT01282424
+## '''Update:''' '''Abstract:''' Ajay K. Gopal, MD, Brad S. Kahl, MD, Sven de Vos, MD, PhD, Nina D. Wagner-Johnston, MD, Stephen J. Schuster, MD, Wojciech Jurczak, MD, PhD, Ian W. Flinn, MD, PhD, Christopher R. Flowers, MD, Peter Martin, MD, Andreas Viardot, MD, Kristie A. Blum, MD, Andre Goy, MD, Andrew Davies, BM PhD, Pier Luigi Zinzani, MD, Martin H. Dreyling, MD, PhD, Leanne M. Holes, Bess Sorensen, PhD, Wayne R. Godfrey, MD and Gilles Andre Salles, MD, PhD. Mature Follow up from a Phase 2 Study of PI3K-Delta Inhibitor Idelalisib in Patients with Double (Rituximab and Alkylating agent)-Refractory Indolent B-Cell Non-Hodgkin Lymphoma (iNHL). ASH Annual Meeting 2014, Abstract 1708 [https://ash.confex.com/ash/2014/webprogram/Paper74940.html link to abstract]
+==Ibrutinib monotherapy {{#subobject:af879d|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 80 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:dd21e8|Variant=1}}===
+===Regimen {{#subobject:b44969|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable" style="color:white; background-color:#404040"
-! style="width: 20%" |Study
+|<small>'''FDA-recommended dose'''</small>
-! style="width: 20%" |Years of enrollment
+|-
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+|}
-! style="width: 20%" |Comparator
+{| class="wikitable sortable" style="width: 80%; text-align:center;"
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 25%"|Study
+!style="width: 25%"|Years 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/PMC5399483/ Noy et al. 2017 (PCYC-1121-CA)]
+|2013-2015
+|style="background-color:#91cf61"|Phase 2 (RT)
+| style="background-color:#8c96c6" |ORR: 48% (95% CI, 35-62)
 |-
-|[https://doi.org/10.1200/JCO.2013.53.6136 Satoh et al. 2014 (TyTAN)]
+|}
-|2007-2009
+<div class="toccolours" style="background-color:#b3e2cd">
-| style="background-color:#1a9851" |Phase 3 (C)
+====Targeted therapy====
-|[[#Lapatinib_.26_Paclitaxel_99|Lapatinib & Paclitaxel]]
+*[[Ibrutinib (Imbruvica)]] 560 mg PO once per day
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 8.9 vs 11 mo<br>(HR 1.19, 95% CI 0.90-1.56)
+'''Continued indefinitely'''
+</div></div>
+===References===
+<!-- #'''Abstract:''' Ariela Noy, MD, PhD, Sven de Vos, MD, PhD, Catherine Thieblemont, MD, PhD, Peter Martin, MD, Christopher Flowers, MD, MS, Franck Morschhauser, MD, PhD, Graham P. Collins, MD, PhD, Shuo Ma, Morton Coleman, MD, Shachar Peles, MD, Stephen Smith, MD, Alina Smith, Brian Munneke, PhD, Isaiah Dimery, MD, Darrin Beaupre, MD, PhD and Robert W Chen, MD. Single-Agent Ibrutinib Demonstrates Efficacy and Safety in Patients with Relapsed/Refractory Marginal Zone Lymphoma: A Multicenter, Open-Label, Phase 2 Study. ASH 2016 Annual Meeting Abstract 1213. [https://ash.confex.com/ash/2016/webprogram/Paper89393.html link to abstract] [https://clinicaltrials.gov/ct2/show/NCT01980628 ClinicalTrials.gov info] -->
+# '''PCYC-1121-CA:''' Noy A, de Vos S, Thieblemont C, Martin P, Flowers CR, Morschhauser F, Collins GP, Ma S, Coleman M, Peles S, Smith S, Barrientos JC, Smith A, Munneke B, Dimery I, Beaupre DM, Chen R. Targeting Bruton tyrosine kinase with ibrutinib in relapsed/refractory marginal zone lymphoma. Blood. 2017 Apr 20;129(16):2224-2232. Epub 2017 Feb 6. [http://www.bloodjournal.org/content/129/16/2224.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5399483/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28167659 PubMed] NCT01980628
+##'''Update:''' Noy A, de Vos S, Coleman M, Martin P, Flowers CR, Thieblemont C, Morschhauser F, Collins GP, Ma S, Peles S, Smith SD, Barrientos JC, Chong E, Wu S, Cheung LW, Kwei K, Hauns B, Arango-Hisijara I, Chen R. Durable ibrutinib responses in relapsed/refractory marginal zone lymphoma: long-term follow-up and biomarker analysis. Blood Adv. 2020 Nov 24;4(22):5773-5784. [https://doi.org/10.1182/bloodadvances.2020003121 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7686907/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33227125/ PubMed]
+==Ox-P {{#subobject:401729|Regimen=1}}==
+Ox-P: '''<u>Ox</u>'''aliplatin & '''<u>P</u>'''rednisone
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:675076|Variant=1}}===
+{| class="wikitable" style="width: 40%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1056/nejmoa2004413 Shitara et al. 2020 (DESTINY-Gastric01)]
+|[http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1099650 Oh et al. 2016 (CISL)]
-|2017-2019
+|style="background-color:#91cf61"|Phase 2
-| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
-| style="background-color:#d73027" |Inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#fdcdac">
+''Note: the treatment details state that prednisone was used, but later in the text prednisolone is mentioned. The authors have been contacted for clarification.''
-====Biomarker eligibility criteria====
-*HER2-positive disease
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
-'''28-day cycles'''
+====Glucocorticoid therapy====
+*[[Prednisone (Sterapred)]] 100 mg PO once per day on days 1 to 5 (see note)
+'''21-day cycle for up to 6 cycles'''
+</div></div>
+===References===
+# Oh SY, Kim WS, Kim JS, Chae YS, Lee GW, Eom HS, Ryoo HM, Lee S, Kim SJ, Yoon DH, Won JH, Hong J, Park J, Lee SM, Hong JY, Park E, Kim HJ, Yang DH, Kim HJ, Suh C. A phase II study of oxaliplatin and prednisone for patients with relapsed or refractory marginal zone lymphoma: Consortium for Improving Survival of Lymphoma trial. Leuk Lymphoma. 2016;57(6):1406-12. [http://www.tandfonline.com/doi/full/10.3109/10428194.2015.1099650 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26413982 PubMed]
+==Vorinostat monotherapy {{#subobject:1d4752|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:f64907|Variant=1}}===
+{| class="wikitable" style="width: 40%; text-align:center;"
+!style="width: 25%"|Study
+!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ Kirschbaum et al. 2011 (PHII-63)]
+|style="background-color:#ffffbe"|Phase 2, <20 pts in subgroup
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Vorinostat (Zolinza)]] 200 mg PO twice per day on days 1 to 14
+'''21-day cycles'''
 </div></div>
 ===References===
-#'''TyTAN:''' Satoh T, Xu RH, Chung HC, Sun GP, Doi T, Xu JM, Tsuji A, Omuro Y, Li J, Wang JW, Miwa H, Qin SK, Chung IJ, Yeh KH, Feng JF, Mukaiyama A, Kobayashi M, Ohtsu A, Bang YJ. Lapatinib plus paclitaxel versus paclitaxel alone in the second-line treatment of HER2-amplified advanced gastric cancer in Asian populations: TyTAN--a randomized, phase III study. J Clin Oncol. 2014 Jul 1;32(19):2039-49. Epub 2014 May 27. [https://doi.org/10.1200/JCO.2013.53.6136 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24868024 PubMed] NCT00486954
+# '''PHII-63:''' Kirschbaum M, Frankel P, Popplewell L, Zain J, Delioukina M, Pullarkat V, Matsuoka D, Pulone B, Rotter AJ, Espinoza-Delgado I, Nademanee A, Forman SJ, Gandara D, Newman E. Phase II study of vorinostat for treatment of relapsed or refractory indolent non-Hodgkin's lymphoma and mantle cell lymphoma. J Clin Oncol. 2011 Mar 20;29(9):1198-203. Epub 2011 Feb 7. [https://doi.org/10.1200/jco.2010.32.1398 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083875/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21300924 PubMed] NCT00253630
-#'''GATSBY:''' Thuss-Patience PC, Shah MA, Ohtsu A, Van Cutsem E, Ajani JA, Castro H, Mansoor W, Chung HC, Bodoky G, Shitara K, Phillips GDL, van der Horst T, Harle-Yge ML, Althaus BL, Kang YK. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017 May;18(5):640-653. Epub 2017 Mar 23. [https://doi.org/10.1016/S1470-2045(17)30111-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28343975 PubMed] NCT01641939
+==Zanubrutinib monotherapy {{#subobject:ea485a|Regimen=1}}==
-#'''DESTINY-Gastric01:''' Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2004413 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469182 PubMed] NCT03329690
-==Paclitaxel & Ramucirumab {{#subobject:fdd93f|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:f66446|Variant=1}}===
+===Regimen {{#subobject:44abc0|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable" style="color:white; background-color:#404040"
-! style="width: 20%" |Study
+|<small>'''FDA-recommended dose'''</small>
-! style="width: 20%" |Years of enrollment
+|-
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+|}
-! style="width: 20%" |Comparator
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 33%"|Study
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6742923/ Tam et al. 2019 (BGB-3111-AU-003)]
+|2014-2018
+| style="background-color:#91cf61" |Phase 1/2 (RT)
 |-
-|Awaiting publication (DESTINY-Gastric04)
+|[https://doi.org/10.1158/1078-0432.ccr-21-1704 Opat et al. 2021 (MAGNOLIA)]
-|2021-ongoing
+|2019-2020
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#91cf61" |Phase 2 (RT)
-|[[#Trastuzumab_deruxtecan_monotherapy|Trastuzumab deruxtecan]]
-| style="background-color:#d3d3d3" |In progress
 |-
 |}
-''Note: Dosing information is from CT.gov.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Ramucirumab (Cyramza)]] 8 mg/kg IV once per day on days 1 & 15
+*[[Zanubrutinib (Brukinsa)]] 160 mg PO twice per day
-====Chemotherapy====
-*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 '''28-day cycles'''
 </div></div>
 ===References===
-#'''DESTINY-Gastric04:''' NCT04704934
+# '''BGB-3111-AU-003:''' Tam CS, Trotman J, Opat S, Burger JA, Cull G, Gottlieb D, Harrup R, Johnston PB, Marlton P, Munoz J, Seymour JF, Simpson D, Tedeschi A, Elstrom R, Yu Y, Tang Z, Han L, Huang J, Novotny W, Wang L, Roberts AW. Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Blood. 2019 Sep 12;134(11):851-859. Epub 2019 Jul 24. [https://doi.org/10.1182/blood.2019001160 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6742923/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31340982/ PubMed] NCT02343120
-[[Category:Gastric cancer regimens]]
+##'''Update:''' Phillips T, Chan H, Tam CS, Tedeschi A, Johnston P, Oh SY, Opat S, Eom HS, Allewelt H, Stern JC, Tan Z, Novotny W, Huang J, Trotman J. Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Blood Adv. 2022 Jun 14;6(11):3472-3479. [https://doi.org/10.1182/bloodadvances.2021006083 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9198905/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35390135/ PubMed]
-[[Category:Biomarker-specific pages]]
+# '''MAGNOLIA:''' Opat S, Tedeschi A, Linton K, McKay P, Hu B, Chan H, Jin J, Sobieraj-Teague M, Zinzani PL, Coleman M, Thieblemont C, Browett P, Ke X, Sun M, Marcus R, Portell CA, Ardeshna K, Bijou F, Walker P, Hawkes EA, Mapp S, Ho SJ, Talaulikar D, Zhou KS, Co M, Li X, Zhou W, Cappellini M, Tankersley C, Huang J, Trotman J. The MAGNOLIA Trial: Zanubrutinib, a Next-Generation Bruton Tyrosine Kinase Inhibitor, Demonstrates Safety and Efficacy in Relapsed/Refractory Marginal Zone Lymphoma. Clin Cancer Res. 2021 Dec 1;27(23):6323-6332. Epub 2021 Sep 15. [https://doi.org/10.1158/1078-0432.ccr-21-1704 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34526366/ PubMed] NCT03846427
-[[Category:Gastroesophageal cancers]]
+=Response criteria=
+==NCI Sponsored International Working Group Criteria (1999)==
+# Cheson BD, Horning SJ, Coiffier B, Shipp MA, Fisher RI, Connors JM, Lister TA, Vose J, Grillo-López A, Hagenbeek A, Cabanillas F, Klippensten D, Hiddemann W, Castellino R, Harris NL, Armitage JO, Carter W, Hoppe R, Canellos GP. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999 Apr;17(4):1244. Review. Erratum in: J Clin Oncol 2000 Jun;18(11):2351. [https://doi.org/10.1200/jco.1999.17.4.1244 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561185 PubMed]
+[[Category:Marginal zone lymphoma regimens]]
+[[Category:Disease-specific pages]]
+[[Category:Indolent lymphomas]]
+[[Category:Non-Hodgkin lymphomas]]

Difference between revisions of "Staging page"

Revision as of 16:09, 15 October 2022

Guidelines

ESMO

Older

NCCN

First-line therapy, randomized data

Bendamustine & Rituximab (BR)

Regimen

Chemotherapy

Targeted therapy

Supportive therapy

References

Chlorambucil monotherapy

Regimen

Chemotherapy

Supportive therapy

References

Fludarabine monotherapy

Regimen

Chemotherapy

Supportive therapy

References

Ibrutinib monotherapy

Regimen

Targeted therapy

References

R-CHOP

Example orders

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

References

R-CVP

Regimen

Targeted therapy

Chemotherapy

Glucocorticoid therapy

Supportive therapy

References

Rituximab monotherapy

Regimen

Targeted therapy

Supportive therapy

Subsequent treatment

References

First-line therapy, non-randomized or retrospective data

Ibritumomab tiuxetan protocol

Regimen

Targeted therapy

Radioconjugate therapy

References

Lenalidomide & Rituximab (R2)

Regimen

Targeted therapy

References

PCR

Regimen

Chemotherapy

Targeted therapy

Supportive therapy

References

Consolidation after first-line therapy

Rituximab monotherapy

Regimen

Preceding treatment

Targeted therapy

References

Relapsed or refractory, randomized data

Lenalidomide & Rituximab (R2)

Regimen

Prior treatment criteria

Targeted therapy

References

Rituximab monotherapy

Regimen variant #1, 4-week course

Preceding treatment

Targeted therapy

Lenalidomide & Rituximab (R²)

Lenalidomide & Rituximab (R²)