Diffuse large B cell lymphoma medical therapy: Difference between revisions
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==Overview== | ==Overview== | ||
The optimal therapy for diffuse large B cell lymphoma depends on the stage at diagnosis,age, IPI (International Prognostic Index) and aaIPI (Age adjusted International Prognostic index). The predominant therapy for diffuse large B cell lymphoma is chemotherapy. Adjunctive radiotherapy may be required. Inclusion in a clinical trial is recommended when available. | The optimal therapy for diffuse large B cell lymphoma depends on the stage at diagnosis,age, [[IPI (International Prognostic Index)]] and [[aaIPI (Age adjusted International Prognostic index)]]. The predominant therapy for diffuse large B cell lymphoma is [[chemotherapy]]. Adjunctive [[radiotherapy]] may be required. Inclusion in a clinical trial is recommended when available. | ||
==Medical Therapy== | ==Medical Therapy== | ||
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=== Stem Cell Transplantation === | === Stem Cell Transplantation === | ||
High dose Chemotherapy coupled with stem cell transplantation is sometimes used to treat patients whose disease is refractory or relapsed following initial chemotherapy. Most common is Autologous stem cell transplant in which patients receive their own stem cells. Other option is Allogenic stem cell transplant in which patient will receive stem cells from a donor | High dose Chemotherapy coupled with stem cell transplantation is sometimes used to treat patients whose disease is refractory or relapsed following initial chemotherapy. Most common is [[Autologous stem cell transplant]] in which patients receive their own stem cells. Other option is [[Allogenic stem cell transplant]] in which patient will receive stem cells from a [[donor]] | ||
=== Regimens of Chemotherapy === | === Regimens of Chemotherapy === | ||
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==== non Bulky with aaPI Low-Intermediate risk ( 1 ) OR aaPI Low ( 0 ) with Bulky Disease ==== | ==== non Bulky with aaPI Low-Intermediate risk ( 1 ) OR aaPI Low ( 0 ) with Bulky Disease ==== | ||
* Six Cycles of R-CHOP given every 21 days plus Radiotherapy is recommended along with chemotherapy in this group | * Six Cycles of R-CHOP given every 21 days plus Radiotherapy is recommended along with chemotherapy in this group | ||
* Alteranative treatment can include intensive immunochemotherapy with R-ACVBP( Dose intensive Rituximab, Doxorubicin, Cyclophosphamide, Vindesine, Bleomycin and Prednisone) with subsequent consolidation therapy and can improve survival. | * Alteranative treatment can include intensive immunochemotherapy with [[R-ACVBP]]( Dose intensive Rituximab, Doxorubicin, Cyclophosphamide, Vindesine, Bleomycin and Prednisone) with subsequent [[consolidation therapy]] and can improve survival. Radiotherapy is not recommended in this regimen<ref name="pmid22118442">{{cite journal| author=Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O et al.| title=Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. | journal=Lancet | year= 2011 | volume= 378 | issue= 9806 | pages= 1858-67 | pmid=22118442 | doi=10.1016/S0140-6736(11)61040-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22118442 }} </ref>. | ||
==== Intermediate High risk or High Risk ( > or equal to 2 ) ==== | ==== Intermediate High risk or High Risk ( > or equal to 2 ) ==== | ||
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* Inclusion in Clinical Trial is recommended | * Inclusion in Clinical Trial is recommended | ||
* Eight cycles of R-CHOP given every 21 days is most frequently used therapy | * Eight cycles of R-CHOP given every 21 days is most frequently used therapy | ||
* Intensive treatment with R-ACVBP or R-CHOEP is also used sometimes<ref name="pmid21546499">{{cite journal| author=Fitoussi O, Belhadj K, Mounier N, Parrens M, Tilly H, Salles G et al.| title=Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA. | journal=Haematologica | year= 2011 | volume= 96 | issue= 8 | pages= 1136-43 | pmid=21546499 | doi=10.3324/haematol.2010.038109 | pmc=3148907 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21546499 }} </ref> | * Intensive treatment with [[R-ACVBP]] or [[R-CHOEP-14 regimen|R-CHOEP]] is also used sometimes<ref name="pmid21546499">{{cite journal| author=Fitoussi O, Belhadj K, Mounier N, Parrens M, Tilly H, Salles G et al.| title=Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA. | journal=Haematologica | year= 2011 | volume= 96 | issue= 8 | pages= 1136-43 | pmid=21546499 | doi=10.3324/haematol.2010.038109 | pmc=3148907 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21546499 }} </ref> | ||
=== <u>Age 60-80 years</u> === | === <u>Age 60-80 years</u> === | ||
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=== <u>Age more than 80 years</u> === | === <u>Age more than 80 years</u> === | ||
* The elderly are usually unable to tolerate therapy well. Multiple lower intensity regimens have been attempted in this age group<ref>{{cite journal |doi=10.1080/10428190600799946 |pmid=17071492 |title=CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma |journal=Leukemia & Lymphoma |volume=47 |issue=10 |pages=2174–80 |year=2006 |last1=Zaja |first1=F. |last2=Tomadini |first2=V. |last3=Zaccaria |first3=A. |last4=Lenoci |first4=M. |last5=Battista |first5=M. |last6=Molinari |first6=A. L. |last7=Fabbri |first7=A. |last8=Battista |first8=R. |last9=Cabras |first9=M. G. |last10=Gallamini |first10=A. |last11=Fanin |first11=R. }}</ref> | * The elderly are usually unable to tolerate therapy well. Multiple lower intensity regimens have been attempted in this age group<ref>{{cite journal |doi=10.1080/10428190600799946 |pmid=17071492 |title=CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma |journal=Leukemia & Lymphoma |volume=47 |issue=10 |pages=2174–80 |year=2006 |last1=Zaja |first1=F. |last2=Tomadini |first2=V. |last3=Zaccaria |first3=A. |last4=Lenoci |first4=M. |last5=Battista |first5=M. |last6=Molinari |first6=A. L. |last7=Fabbri |first7=A. |last8=Battista |first8=R. |last9=Cabras |first9=M. G. |last10=Gallamini |first10=A. |last11=Fanin |first11=R. }}</ref> | ||
* Attenuated Chemotherapy also known as R mini-CHOP is used and is associate with improved outcome in these patients<ref name="pmid21482186">{{cite journal| author=Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S et al.| title=Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. | journal=Lancet Oncol | year= 2011 | volume= 12 | issue= 5 | pages= 460-8 | pmid=21482186 | doi=10.1016/S1470-2045(11)70069-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21482186 }} </ref> | * Attenuated Chemotherapy also known as [[R mini-CHOP]] is used and is associate with improved outcome in these patients<ref name="pmid21482186">{{cite journal| author=Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S et al.| title=Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial. | journal=Lancet Oncol | year= 2011 | volume= 12 | issue= 5 | pages= 460-8 | pmid=21482186 | doi=10.1016/S1470-2045(11)70069-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21482186 }} </ref> | ||
* In Patients with Cardiac Dysfunction, Doxorubicin can be replaced with other chemotherapeutic agents like Etoposide, Gemcitabine or Liposomal doxorubicin<ref name="pmid24220559">{{cite journal| author=Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P et al.| title=De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial. | journal=J Clin Oncol | year= 2014 | volume= 32 | issue= 4 | pages= 282-7 | pmid=24220559 | doi=10.1200/JCO.2013.49.7586 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24220559 }} </ref> | * In Patients with Cardiac Dysfunction, Doxorubicin can be replaced with other chemotherapeutic agents like [[Etoposide]], [[Gemcitabine]] or [[Liposomal doxorubicin]]<ref name="pmid24220559">{{cite journal| author=Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P et al.| title=De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial. | journal=J Clin Oncol | year= 2014 | volume= 32 | issue= 4 | pages= 282-7 | pmid=24220559 | doi=10.1200/JCO.2013.49.7586 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24220559 }} </ref> | ||
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Revision as of 22:45, 23 July 2018
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3)Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Anila Hussain, MD [2], Sowminya Arikapudi, M.B,B.S. [3]
Overview
The optimal therapy for diffuse large B cell lymphoma depends on the stage at diagnosis,age, IPI (International Prognostic Index) and aaIPI (Age adjusted International Prognostic index). The predominant therapy for diffuse large B cell lymphoma is chemotherapy. Adjunctive radiotherapy may be required. Inclusion in a clinical trial is recommended when available.
Medical Therapy
Chemotherapy
Main treatment of Choice for DLBCL. Chemotherapy is administered intravenously and people receiving chemotherapy commonly have a (peripherally inserted central catheter) in their arm near the elbow or a surgically implanted medical port. It is most effective when it is administered multiple times over a period of months (e.g. every 3 weeks, over 6 to 8 cycles). Different regimens of Chemotherapy with different durations/Cycles are used depending on the stage of disease, age of patient and prognsotic index. In general
- Patients with limited stage disease receive 3 cycles of therapy
- Patients with extensive disease 6 or 8 cycles of chemotherapy. In the United States, 6 cycles is the preferred approach rather than 8 cycles.
Radiation therapy
Radiation is often added in the treatment. It is used commonly after completing 3 cycles of treatment in limited stage disease. In extensive disease, after 6-8 cycles of chemotherapy, radiation can be used at the end of the treatment to areas of bulky involvement. Radiation therapy alone is not an effective treatment for this disease
Stem Cell Transplantation
High dose Chemotherapy coupled with stem cell transplantation is sometimes used to treat patients whose disease is refractory or relapsed following initial chemotherapy. Most common is Autologous stem cell transplant in which patients receive their own stem cells. Other option is Allogenic stem cell transplant in which patient will receive stem cells from a donor
Regimens of Chemotherapy
1) R-CHOP
- Standard treatment is CHOP-R, also referred to as R-CHOP, an improved form of CHOP with the addition of rituximab (Rituxan), which has increased the rates of complete responses for Diffuse large B cell lymphoma patients, particularly elderly patients.[1][2][3]
R-CHOP is a combination of one monoclonal antibody, 3 chemotherapy drugs and one steroid:[4]
- Rituximab (Rituxan)
- Cyclophosphamide (Cytoxan)
- Doxorubicin (Hydroxydaunorubicin)
- Vincristine (Oncovin)
- Prednisone
2) R-ACVBP
Alternate Intensive immmunochemotherapy, which is a combination of:
- Rituximab
- Doxorubicin
- Cyclophosphamide
- Vindesine
- Bleomycin
- Prednisone
3) R-CHOEP
- Rituximab
- Cyclophosphamide
- Doxorubicin
- Vincristine
- etoposide
- Prednisolone
Age Based Treatment Approach:
Age less than or equal to 60 years:
Non-Bulky Disease with aaPI Low ( 0 )
- Six Cycles of R-CHOP given every 21 days[5]
- Radiotherapy Consolidation treatment has no proven benefit in patients with non bulky disease
non Bulky with aaPI Low-Intermediate risk ( 1 ) OR aaPI Low ( 0 ) with Bulky Disease
- Six Cycles of R-CHOP given every 21 days plus Radiotherapy is recommended along with chemotherapy in this group
- Alteranative treatment can include intensive immunochemotherapy with R-ACVBP( Dose intensive Rituximab, Doxorubicin, Cyclophosphamide, Vindesine, Bleomycin and Prednisone) with subsequent consolidation therapy and can improve survival. Radiotherapy is not recommended in this regimen[6].
Intermediate High risk or High Risk ( > or equal to 2 )
- No current standard therapy
- Inclusion in Clinical Trial is recommended
- Eight cycles of R-CHOP given every 21 days is most frequently used therapy
- Intensive treatment with R-ACVBP or R-CHOEP is also used sometimes[7]
Age 60-80 years
- Detailed Geriatric assessment should be done to assess co-morbidities and functional decline to decide upon the treatment of choice[8]
- Current Standard treatment is R-CHOP and include 8 Doses of Rituximab given every 21 days with 6-8 cycles of Combination Chemotherapy with CHOP[9]
- Radiotherapy can improve outcome in patients in this age group with bulky disease[10]
A new development is obtaining a PET scan after completing two cycles of chemotherapy, to help make further decisions after chemotherapy.
Age more than 80 years
- The elderly are usually unable to tolerate therapy well. Multiple lower intensity regimens have been attempted in this age group[11]
- Attenuated Chemotherapy also known as R mini-CHOP is used and is associate with improved outcome in these patients[12]
- In Patients with Cardiac Dysfunction, Doxorubicin can be replaced with other chemotherapeutic agents like Etoposide, Gemcitabine or Liposomal doxorubicin[13]
.
References
- ↑ Sehn, L. H.; Berry, B.; Chhanabhai, M.; Fitzgerald, C.; Gill, K.; Hoskins, P.; Klasa, R.; Savage, K. J.; Shenkier, T.; Sutherland, J.; Gascoyne, R. D.; Connors, J. M. (2007). "The revised International Prognostic Index (R-IPI) is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP". Blood. 109 (5): 1857–61. doi:10.1182/blood-2006-08-038257. PMID 17105812.
- ↑ Miyazaki K (2016). "Treatment of Diffuse Large B-Cell Lymphoma". J Clin Exp Hematop. 56 (2): 79–88. doi:10.3960/jslrt.56.79. PMID 27980306.
- ↑ http://cornell-lymphoma.com/tag/dlbcl/[full citation needed]
- ↑ Farber, Charles M.; Axelrod, Randy C. (2011). "The Clinical and Economic Value of Rituximab for the Treatment of Hematologic Malignancies". Contemporary Oncology. 3 (1).
- ↑ Pfreundschuh M, Kuhnt E, Trumper L et al. CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-celllymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol 2011; 12: 1013–1022
- ↑ Récher C, Coiffier B, Haioun C, Molina TJ, Fermé C, Casasnovas O; et al. (2011). "Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B-cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial". Lancet. 378 (9806): 1858–67. doi:10.1016/S0140-6736(11)61040-4. PMID 22118442.
- ↑ Fitoussi O, Belhadj K, Mounier N, Parrens M, Tilly H, Salles G; et al. (2011). "Survival impact of rituximab combined with ACVBP and upfront consolidation autotransplantation in high-risk diffuse large B-cell lymphoma for GELA". Haematologica. 96 (8): 1136–43. doi:10.3324/haematol.2010.038109. PMC 3148907. PMID 21546499.
- ↑ Morrison VA, Hamlin P, Soubeyran P, Stauder R, Wadhwa P, Aapro M; et al. (2015). "Diffuse large B-cell lymphoma in the elderly: impact of prognosis, comorbidities, geriatric assessment, and supportive care on clinical practice. An International Society of Geriatric Oncology (SIOG) expert position paper". J Geriatr Oncol. 6 (2): 141–52. doi:10.1016/j.jgo.2014.11.004. PMID 25491101.
- ↑ Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S; et al. (2010). "Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte". Blood. 116 (12): 2040–5. doi:10.1182/blood-2010-03-276246. PMC 2951853. PMID 20548096.
- ↑ Held G, Murawski N, Ziepert M, Fleckenstein J, Pöschel V, Zwick C; et al. (2014). "Role of radiotherapy to bulky disease in elderly patients with aggressive B-cell lymphoma". J Clin Oncol. 32 (11): 1112–8. doi:10.1200/JCO.2013.51.4505. PMID 24493716.
- ↑ Zaja, F.; Tomadini, V.; Zaccaria, A.; Lenoci, M.; Battista, M.; Molinari, A. L.; Fabbri, A.; Battista, R.; Cabras, M. G.; Gallamini, A.; Fanin, R. (2006). "CHOP-rituximab with pegylated liposomal doxorubicin for the treatment of elderly patients with diffuse large B-cell lymphoma". Leukemia & Lymphoma. 47 (10): 2174–80. doi:10.1080/10428190600799946. PMID 17071492.
- ↑ Peyrade F, Jardin F, Thieblemont C, Thyss A, Emile JF, Castaigne S; et al. (2011). "Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B-cell lymphoma: a multicentre, single-arm, phase 2 trial". Lancet Oncol. 12 (5): 460–8. doi:10.1016/S1470-2045(11)70069-9. PMID 21482186.
- ↑ Fields PA, Townsend W, Webb A, Counsell N, Pocock C, Smith P; et al. (2014). "De novo treatment of diffuse large B-cell lymphoma with rituximab, cyclophosphamide, vincristine, gemcitabine, and prednisolone in patients with cardiac comorbidity: a United Kingdom National Cancer Research Institute trial". J Clin Oncol. 32 (4): 282–7. doi:10.1200/JCO.2013.49.7586. PMID 24220559.