Follicular lymphoma medical therapy: Difference between revisions

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Latest revision as of 16:42, 23 January 2019

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2]

Overview

The optimal therapy for follicular lymphoma depends on the stage at diagnosis, age, and prognostic scores. The predominant therapy for follicular lymphoma is chemotherapy. Adjunctive hematopoietic stem cell transplantation and radioimmunotherapy may be required.

Medical Therapy

The treatment of follicular lymphoma is based on the stage of the disease^[1]^[2]^[3]^[4]
- For stage 1 and 2, radiotherapy is done.
- For stages 3 and 4, several chemotherapeutic drugs are used for treatment of follicular lymphoma.
- Chemotherapy is started when there is high tumor bulk load which includes the following:
  - A tumor >7 cm in diameter
  - Three nodes in three distinct areas, each >3 cm in diameter
  - Symptomatic spleen enlargement
  - Organ compression
  - Ascites or pleural effusion

Follicular lymphoma

1. Stage 1 and 2:

Radiation doses of 24-30 Gy have been used.

2. High tumor bulk load

2.1. Adult:

- Preferred regime 1. Bendamustine + rituximab - Day 1: Rituximab 375mg/m² IV , Days 1 and 2: Bendamustine 90mg/m² IV over 30–60 minutes. Repeat every 4 weeks for 6 cycles
- Preferred regime 2. Bendamustine + obinutuzumab - Days 1 and 2: Bendamustine 90mg/m² IV Days 1, 8, 15 of Cycle 1: Obintuzumab 1000mg IV followed by: Days 1 and 2: Bendamustine 90mg/m² IV Days 1 of Subsequent Cycles: Obintuzumab 1000mg IV. Repeat every 4 weeks for 6 cycles.
- Preferred regime 3. RCHOP (Category 1) - Day 0: Rituximab 375mg/m² IV Day 1: Cyclophosphamide 750mg/m² IV + doxorubicin 50mg/m² IV + vincristine 1.4mg/m² IV (max 2mg) Days 1–5: Prednisone 100mg/m² orally. Repeat every 3 weeks for 6 to 8 cycles
- Preferred regime 4. CHOP + obinutuzumab - Day 1: Cyclophosphamide 750mg/m² IV + doxorubicin 50mg/m² IV + vincristine 1.4mg/m² IV (max 2mg) Days 1–5: Prednisone 100mg/m² orally Days 1, 8, 15 of Cycle 1: Obintuzumab 1000mg IV followed by: Day 1: Cyclophosphamide 750mg/m² IV + doxorubicin 50mg/m² IV + vincristine 1.4mg/m² IV (max 2mg) Days 1–5: Prednisone 100mg/m² orally Days 1 of Subsequent Cycles: Obintuzumab 1000mg IV. Repeat every 3 weeks for 6 to 8 cycles.
- Alternate regime 1. CVP + obinutuzumab - Day 1: Cyclophosphamide 750mg/v IV + vincristine 1.4mg/v IV (max 2mg) Days 1–5: Prednisone 40mg/v orally Days 1, 8, 15 of Cycle 1: Obintuzumab 1000mg IV followed by: Day 1: Cyclophosphamide 750mg/v IV + vincristine 1.4mg/v IV (max 2mg) Days 1–5: Prednisone 40mg/m² orally Days 1 of Subsequent Cycles: Obintuzumab 1000mg IV. Repeat every 3 weeks for 6 to 8 cycles
- Alternate regime 2. Rituximab, Day 1: Rituximab 375mg/m² IV. Repeat every 7 days for 4 cycles

2.2. Elderly

Preferred regime 1. Rituximab 375mg/m² IV. Repeat every 7 days for 4 cycles
Preferred regime 2. Single agent alkylator ± rituximab - Chlorambucil 0.1mg/kg/day for 45 days then on days 1–15, monthly for 4 months • Rituximab 375mg/m² weekly for 4 doses, then monthly for 4 infusions

3. Consolidation and extended dosing

Rituximab maintenance - Day 1: Rituximab 375mg/m² IV. Repeat every 8 weeks for 12 cycles for patients initially presenting with high tumor burden.
Obinutuzumab maintenance - Day 1: Obinutuzumab 1000 mg IV. Repeat every 8 weeks for 12 cycles.
Radioimmunotherapy - 90Yttrium-ibritumomab-tiuxetan 15 MBq/kg (0.4 mCi/kg) single dose after induction with chemotherapy.

High-dose therapy with autologous stem cell rescue and Allogeneic stem cell transplant for highly selected patients.

References

↑ Tan D, Horning SJ, Hoppe RT, Levy R, Rosenberg SA, Sigal BM; et al. (2013). "Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience". Blood. 122 (6): 981–7. doi:10.1182/blood-2013-03-491514. PMC 3739040. PMID 23777769.
↑ McNamara C, Davies J, Dyer M, Hoskin P, Illidge T, Lyttelton M; et al. (2012). "Guidelines on the investigation and management of follicular lymphoma". Br J Haematol. 156 (4): 446–67. doi:10.1111/j.1365-2141.2011.08969.x. PMID 22211428.
↑ Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P; et al. (2014). "Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial". Lancet Oncol. 15 (4): 424–35. doi:10.1016/S1470-2045(14)70027-0. PMID 24602760.
↑ Dreyling M, Ghielmini M, Rule S, Salles G, Vitolo U, Ladetto M; et al. (2016). "Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Ann Oncol. 27 (suppl 5): v83–v90. doi:10.1093/annonc/mdw400. PMID 27664263.

[pmid23777769-1] Tan D, Horning SJ, Hoppe RT, Levy R, Rosenberg SA, Sigal BM; et al. (2013). "Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience". Blood. 122 (6): 981–7. doi:10.1182/blood-2013-03-491514. PMC 3739040. PMID 23777769.

[pmid22211428-2] McNamara C, Davies J, Dyer M, Hoskin P, Illidge T, Lyttelton M; et al. (2012). "Guidelines on the investigation and management of follicular lymphoma". Br J Haematol. 156 (4): 446–67. doi:10.1111/j.1365-2141.2011.08969.x. PMID 22211428.

[pmid24602760-3] Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P; et al. (2014). "Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial". Lancet Oncol. 15 (4): 424–35. doi:10.1016/S1470-2045(14)70027-0. PMID 24602760.

[pmid27664263-4] Dreyling M, Ghielmini M, Rule S, Salles G, Vitolo U, Ladetto M; et al. (2016). "Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up". Ann Oncol. 27 (suppl 5): v83–v90. doi:10.1093/annonc/mdw400. PMID 27664263.

[1]

[2]

[3]

[4]

@@ Line 1: / Line 1: @@
 __NOTOC__
 {{Follicular lymphoma}}
-{{CMG}}
+{{CMG}} {{AE}} {{AS}}
 ==Overview==
+The optimal therapy for follicular lymphoma depends on the stage at diagnosis, age, and prognostic scores. The predominant therapy for follicular lymphoma is [[chemotherapy]]. Adjunctive hematopoietic [[stem cell transplantation]] and [[radioimmunotherapy]] may be required.
 ==Medical Therapy==
-There is no consensus regarding the best treatment protocol. Several considerations should be taken into account including age, stage, and prognostic scores.
+* The treatment of follicular lymphoma is based on the stage of the disease<ref name="pmid23777769">{{cite journal| author=Tan D, Horning SJ, Hoppe RT, Levy R, Rosenberg SA, Sigal BM et al.| title=Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience. | journal=Blood | year= 2013 | volume= 122 | issue= 6 | pages= 981-7 | pmid=23777769 | doi=10.1182/blood-2013-03-491514 | pmc=3739040 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23777769  }} </ref><ref name="pmid22211428">{{cite journal| author=McNamara C, Davies J, Dyer M, Hoskin P, Illidge T, Lyttelton M et al.| title=Guidelines on the investigation and management of follicular lymphoma. | journal=Br J Haematol | year= 2012 | volume= 156 | issue= 4 | pages= 446-67 | pmid=22211428 | doi=10.1111/j.1365-2141.2011.08969.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22211428  }} </ref><ref name="pmid24602760">{{cite journal| author=Ardeshna KM, Qian W, Smith P, Braganca N, Lowry L, Patrick P et al.| title=Rituximab versus a watch-and-wait approach in patients with advanced-stage, asymptomatic, non-bulky follicular lymphoma: an open-label randomised phase 3 trial. | journal=Lancet Oncol | year= 2014 | volume= 15 | issue= 4 | pages= 424-35 | pmid=24602760 | doi=10.1016/S1470-2045(14)70027-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24602760  }} </ref><ref name="pmid27664263">{{cite journal| author=Dreyling M, Ghielmini M, Rule S, Salles G, Vitolo U, Ladetto M et al.| title=Newly diagnosed and relapsed follicular lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. | journal=Ann Oncol | year= 2016 | volume= 27 | issue= suppl 5 | pages= v83-v90 | pmid=27664263 | doi=10.1093/annonc/mdw400 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27664263  }} </ref>
-*Patients with advanced disease who are asymptomatic might benefit from a watch and wait approach as early treatment does not provide survival benefit.<ref>Follicular Lymphoma: Perspective, Treatment Options, and Strategy by T. Andrew Lister, MD, FRCP, http://www.medscape.org/viewarticle/709528_transcript</ref><ref>Watchful Waiting in Low–Tumor Burden Follicular Lymphoma in the Rituximab Era: Results of an F2-Study Database http://jco.ascopubs.org/content/30/31/3848.abstract?sid=40023c4f-fb96-484b-a302-1ade09cc741e</ref>
+** For stage 1 and 2, radiotherapy is done.
-* When patients are symptomatic, specific treatment is required, which might include various combinations of
+** For stages 3 and 4, several chemotherapeutic drugs are used for treatment of follicular lymphoma.
-:* alkylators,
+** Chemotherapy is started when there is high tumor bulk load which includes the following:
-:* [[nucleoside analogues]],
+*** A tumor >7 cm in diameter
-:* [[anthracycline]]-containing regimens (e.g., [[CHOP]]),
+*** Three nodes in three distinct areas, each >3 cm in diameter
-:* monoclonal antibodies [[rituximab]],
+*** Symptomatic spleen enlargement
-:* [[radioimmunotherapy]],
+*** Organ compression
-:* autologous, and allogeneic [[hematopoietic stem cell transplantation]].
+*** Ascites or pleural effusion
-* The disease is regarded as incurable (although allogeneic stem cell transplantation may be curative, the [[death|mortality]] from the procedure is too high to be a first line option).
-* The exception is localized disease, which can be cured by local [[irradiation]].
-Personalised idiotype vaccines have shown promise, but have still to prove their efficacy in randomized clinical trials.<ref>{{cite journal |author=Inoges S, de Cerio AL, Soria E, Villanueva H, Pastor F, Bendandi M |title=Idiotype vaccines for human B-cell malignancies |journal=Curr. Pharm. Des. |volume=16 |issue=3 |pages=300–7 |date=January 2010 |pmid=20109139 |doi= 10.2174/138161210790170111|url=http://www.benthamdirect.org/pages/content.php?CPD/2010/00000016/00000003/0006B.SGM}}</ref>
-In 2010 [[Rituximab]] was approved by the EC for first-line maintenance treatment of follicular lymphoma.<ref>{{cite news |url=http://www.genengnews.com/gen-news-highlights/roche-gets-ec-nod-for-follicular-lymphoma-maintenance-therapy/81244149/ |title=Roche Gets EC Nod for Follicular Lymphoma Maintenance Therapy |date=October 29, 2010 }}</ref> Pre-clinical evidence suggests that rituximab could be also used in combination with integrin inhibitors to overcome the resistance to rituximab mediated by stromal cells .<ref>{{Cite journal | last1 = Mraz | first1 = M. | last2 = Zent | first2 = C. S. | last3 = Church | first3 = A. K. | last4 = Jelinek | first4 = D. F. | last5 = Wu | first5 = X. | last6 = Pospisilova | first6 = S. | last7 = Ansell | first7 = S. M. | last8 = Novak | first8 = A. J. | last9 = Kay | first9 = N. E. | last10 = Witzig | doi = 10.1111/j.1365-2141.2011.08794.x | first10 = T. E. | last11 = Nowakowski | first11 = G. S. | title = Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin α-4-β-1 (VLA-4) with natalizumab can overcome this resistance | journal = British Journal of Haematology | volume = 155 | issue = 1 | pages = 53–64 | year = 2011 | pmid = 21749361 | pmc = }}</ref> However, follicular lymphoma which is CD20 negative will not benefit from Rituximab which targets CD20.
-Trial results released in June 2012 show that [[bendamustine]], a drug first developed in East Germany in the 1960s, more than doubled disease progression-free survival when given along with [[rituximab]]. The combination also left patients with fewer side effects than the older treatment (a combination of five drugs—rituximab, cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine and prednisone, collectively called [[R-CHOP]]).<ref>{{cite news |url=http://health.usnews.com/health-news/news/articles/2012/06/03/rediscovered-lymphoma-drug-helps-double-survival-study|title='Rediscovered' Lymphoma Drug Helps Double Survival: Study |date=June 3, 2012 }}</ref>
-There are a large number of recent and current clinical trials for follicular lymphoma.<ref>http://clinicaltrials.gov/ct2/results?term=follicular+lymphoma</ref>
-==Drug Regimen==
-* First-line therapy
-:* Preferred Regimen: [[Bendamustine]] {{PLUS}} [[Rituximab]]
-:* Preferred Regimen: RCHOP ([[Rituximab]] {{AND}} [[Cyclophosphamide]] {{AND}} [[Doxorubicin]] {{AND}}[[Vincristine]] {{AND}} [[Prednisone]])
-:* Preferred Regimen: RCHOP ([[Rituximab]] {{AND}} [[Cyclophosphamide]] {{AND}} [[Vincristine]] {{AND}} [[Prednisone]])
-:* Preferred Regimen: [[Rituximab]] (375 mg/m2 weekly for 4 doses)
-* First-line therapy for Elderly
-:* Preferred Regimen: [[Radioimmunotherapy]]
-:* Preferred Regimen: [[Rituximab]] (375 mg/m2 weekly for 4 doses)
-:* Preferred Regimen: Single-agent alkylators ([[Chlorambucil]] {{or}} [[Cyclophosphamide]] +/- [[Rituximab]]
-* First-line consolidation or extended dosing (optional)
-:* Preferred Regimen: [[Radioimmunotherapy]] (after induction with chemotherapy or chemoimmunotherapy)
-:* Preferred Regimen: [[Rituximab]] (maintenance 375 mg/m2 one dose every 8 weeks for 12 doses for patients initially presenting with high tumor burden)
-:* Preferred Regimen: [[Rituximab]] (maintenance 375 mg/m2 one dose every 8 weeks for 4 doses for patients initially treated with single agent rituximab)
-* Second-line and subsequent therapy
-:* Preferred Regimen: Chemoimmunotherapy (as listed under first-line therapy)
-:* Preferred Regimen: FCMR ([[Fludarabine]] {{AND}} [[Cyclophosphamide]] {{AND}} [[Mitoxantrone]] {{AND}} [[Rituximab]])
-:* Preferred Regimen: [[Fludarabine]] {{PLUS}} [[Rituximab]]
-:* Preferred Regimen: [[Idelalisib]]
-:* Preferred Regimen: [[Lenalidomide]] +/- [[Rituximab]]
-:* Preferred Regimen: [[Radioimmunotherapy]]
-:* Preferred Regimen: [[Rituximab]]
-:* Preferred Regimen: RFND ([[Rituximab]] {{AND}} [[Fludarabine]] {{AND}} [[Mitoxantrone]] {{AND}} [[Dexamethasone]]
-* Second-line Consolidation or Extended Dosing
-:* High-dose therapy with autologous stem cell rescue
-:* Allogenic stem cell transplant for highly selected patients
-:* Rituximab maintenance 375 mg/m2 one dose every 12 weeks for 2 years
-* For patients with locally bulky or locally symptomatic disease, consider ISRT 4-30 Gy +/- additional systemic therapy.
+=== Follicular lymphoma ===
+. Stage 1 and 2:
-* Consider prophylaxis for tumor lysis syndrome.
+* Radiation doses of 24-30 Gy have been used.
+. High tumor bulk load
+.1.  Adult:
+#* Preferred regime 1. '''Bendamustine + rituximab - Day 1: Rituximab 375mg/m<sup>2</sup> IV , Days 1 and 2: Bendamustine 90mg/m<sup>2</sup> IV over 30–60 minutes.'''  '''Repeat every 4 weeks for 6 cycles'''
+#* Preferred regime 2. '''Bendamustine + obinutuzumab - Days 1 and 2: Bendamustine 90mg/m<sup>2</sup> IV'''  '''Days 1, 8, 15 of Cycle 1: Obintuzumab 1000mg IV followed by:'''  '''Days 1 and 2: Bendamustine 90mg/m<sup>2</sup> IV'''  '''Days 1 of Subsequent Cycles: Obintuzumab 1000mg IV.'''  '''Repeat every 4 weeks for 6 cycles.'''
+#* Preferred regime 3. '''RCHOP (Category 1) - Day 0: Rituximab 375mg/m<sup>2</sup> IV'''  '''Day 1: Cyclophosphamide 750mg/m<sup>2</sup> IV + doxorubicin 50mg/m<sup>2</sup> IV + vincristine 1.4mg/m<sup>2</sup> IV (max 2mg)'''  '''Days 1–5: Prednisone 100mg/m<sup>2</sup> orally.'''  '''Repeat every 3 weeks for 6 to 8 cycles'''
+#* Preferred regime 4. '''CHOP + obinutuzumab - Day 1: Cyclophosphamide 750mg/m<sup>2</sup> IV + doxorubicin 50mg/m<sup>2</sup> IV + vincristine 1.4mg/m<sup>2</sup> IV (max 2mg)'''  '''Days 1–5: Prednisone 100mg/m<sup>2</sup> orally'''  '''Days 1, 8, 15 of Cycle 1: Obintuzumab 1000mg IV followed by:'''  '''Day 1: Cyclophosphamide 750mg/m<sup>2</sup> IV + doxorubicin 50mg/m<sup>2</sup> IV + vincristine 1.4mg/m<sup>2</sup> IV (max 2mg)'''  '''Days 1–5: Prednisone 100mg/m<sup>2</sup> orally'''  '''Days 1 of Subsequent Cycles: Obintuzumab 1000mg IV.'''  '''Repeat every 3 weeks for 6 to 8 cycles.'''
+#* Alternate regime 1. '''CVP + obinutuzumab - Day 1: Cyclophosphamide 750mg/v IV + vincristine 1.4mg/v IV (max 2mg)'''  '''Days 1–5: Prednisone 40mg/v orally'''  '''Days 1, 8, 15 of Cycle 1: Obintuzumab 1000mg IV followed by:'''  '''Day 1: Cyclophosphamide 750mg/v IV + vincristine 1.4mg/v IV (max 2mg)'''  '''Days 1–5: Prednisone 40mg/m<sup>2</sup> orally'''  '''Days 1 of Subsequent Cycles: Obintuzumab 1000mg IV.'''  '''Repeat every 3 weeks for 6 to 8 cycles'''
+#* Alternate regime 2. '''Rituximab, Day 1: Rituximab 375mg/m<sup>2</sup> IV.'''  '''Repeat every 7 days for 4 cycles'''
+.2.  Elderly
+* Preferred regime 1. '''Rituximab 375mg/m<sup>2</sup> IV.'''  '''Repeat every 7 days for 4 cycles'''
+* Preferred regime 2. '''Single agent alkylator ± rituximab - Chlorambucil 0.1mg/kg/day for 45 days then on days 1–15, monthly for 4 months'''  '''• Rituximab 375mg/m<sup>2</sup> weekly for 4 doses, then monthly for 4 infusions'''
+. Consolidation and extended dosing
+* '''Rituximab maintenance - Day 1: Rituximab 375mg/m<sup>2</sup> IV.'''  '''Repeat every 8 weeks for 12 cycles for patients initially presenting with high tumor burden.'''
+* '''Obinutuzumab maintenance - Day 1: Obinutuzumab 1000 mg IV.'''  '''Repeat every 8 weeks for 12 cycles.'''
+* '''Radioimmunotherapy - 90Yttrium-ibritumomab-tiuxetan 15 MBq/kg (0.4 mCi/kg) single dose after induction with chemotherapy.'''
+'''High-dose therapy with autologous stem cell rescue and Allogeneic stem cell transplant for highly selected patients.'''
 ==References==
@@ Line 78: / Line 42: @@
 [[Category:Hematology]]
 [[Category:Types of cancer]]
+ [[Category:Up-To-Date]]
+[[Category:Oncology]]
+[[Category:Medicine]]
+[[Category:Hematology]]
+[[Category:Immunology]]