Follicular lymphoma medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Medical Therapy
There is no consensus regarding the best treatment protocol. Several considerations should be taken into account including age, stage, and prognostic scores.
- Patients with advanced disease who are asymptomatic might benefit from a watch and wait approach as early treatment does not provide survival benefit.[1][2]
- When patients are symptomatic, specific treatment is required, which might include various combinations of
- alkylators,
- nucleoside analogues,
- anthracycline-containing regimens (e.g., CHOP),
- monoclonal antibodies rituximab,
- radioimmunotherapy,
- autologous, and allogeneic hematopoietic stem cell transplantation.
- The disease is regarded as incurable (although allogeneic stem cell transplantation may be curative, the 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.[3]
In 2010 Rituximab was approved by the EC for first-line maintenance treatment of follicular lymphoma.[4] 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 .[5] 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).[6]
There are a large number of recent and current clinical trials for follicular lymphoma.[7]
Drug Regimen
- First-line therapy
- Preferred Regimen: Bendamustine Template:PLUS Rituximab
- Preferred Regimen: RCHOP (Rituximab Template:AND Cyclophosphamide Template:AND Doxorubicin Template:ANDVincristine Template:AND Prednisone)
- Preferred Regimen: RCHOP (Rituximab Template:AND Cyclophosphamide Template:AND Vincristine Template: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 Template:AND Cyclophosphamide Template:AND Mitoxantrone Template:AND Rituximab)
- Preferred Regimen: Fludarabine Template:PLUS Rituximab
- Preferred Regimen: Idelalisib
- Preferred Regimen: Lenalidomide +/- Rituximab
- Preferred Regimen: Radioimmunotherapy
- Preferred Regimen: Rituximab
- Preferred Regimen: RFND (Rituximab Template:AND Fludarabine Template:AND Mitoxantrone Template: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.
- Consider prophylaxis for tumor lysis syndrome.
References
- ↑ Follicular Lymphoma: Perspective, Treatment Options, and Strategy by T. Andrew Lister, MD, FRCP, http://www.medscape.org/viewarticle/709528_transcript
- ↑ 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
- ↑ Inoges S, de Cerio AL, Soria E, Villanueva H, Pastor F, Bendandi M (January 2010). "Idiotype vaccines for human B-cell malignancies". Curr. Pharm. Des. 16 (3): 300–7. doi:10.2174/138161210790170111. PMID 20109139.
- ↑ "Roche Gets EC Nod for Follicular Lymphoma Maintenance Therapy". October 29, 2010.
- ↑ Mraz, M.; Zent, C. S.; Church, A. K.; Jelinek, D. F.; Wu, X.; Pospisilova, S.; Ansell, S. M.; Novak, A. J.; Kay, N. E.; Witzig, T. E.; Nowakowski, G. S. (2011). "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". British Journal of Haematology. 155 (1): 53–64. doi:10.1111/j.1365-2141.2011.08794.x. PMID 21749361.
- ↑ "'Rediscovered' Lymphoma Drug Helps Double Survival: Study". June 3, 2012.
- ↑ http://clinicaltrials.gov/ct2/results?term=follicular+lymphoma