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Blood Res 2022; 57(S1):

Published online April 30, 2022

https://doi.org/10.5045/br.2022.2022054

© The Korean Society of Hematology

Treatment of indolent lymphoma

Seong Hyun Jeong

Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea

Correspondence to : Seong Hyun Jeong, M.D.
Department of Hematology-Oncology, Ajou University School of Medicine, 164 World Cup-ro, Yeongtong-gu, Suwon 16499, Korea
E-mail: seonghyunmd@naver.com

Received: March 1, 2022; Revised: April 8, 2022; Accepted: April 21, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Treatment of indolent lymphoma has improved significantly in recent decades since the advent of rituximab (anti-CD20 monoclonal antibody). Although, some patients with limited disease can be cured with radiation therapy alone, most patients experience disease progression and recurrence during follow-up despite early initiation of treatment. Thus, watch-and-wait is still regarded the standard for asymptomatic patients. Patients with indolent lymphoma have a significant heterogeneity in terms of tumor burden, symptoms (according to anatomical sites) and the need for instant therapy. Therefore, the initiation of treatment and treatment option should be decided with a clear goal in each patient according to the need for therapy and clinical benefits with the chosen treatment. In this review, we cover the current treatment of follicular lymphoma and marginal zone lymphoma.

Keywords Indolent lymphoma, Non-Hodgkin’s lymphoma, Follicular lymphoma, Marginal zone lymphoma

Article

Review Article

Blood Res 2022; 57(S1): S120-S129

Published online April 30, 2022 https://doi.org/10.5045/br.2022.2022054

Copyright © The Korean Society of Hematology.

Treatment of indolent lymphoma

Seong Hyun Jeong

Department of Hematology-Oncology, Ajou University School of Medicine, Suwon, Korea

Correspondence to:Seong Hyun Jeong, M.D.
Department of Hematology-Oncology, Ajou University School of Medicine, 164 World Cup-ro, Yeongtong-gu, Suwon 16499, Korea
E-mail: seonghyunmd@naver.com

Received: March 1, 2022; Revised: April 8, 2022; Accepted: April 21, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Treatment of indolent lymphoma has improved significantly in recent decades since the advent of rituximab (anti-CD20 monoclonal antibody). Although, some patients with limited disease can be cured with radiation therapy alone, most patients experience disease progression and recurrence during follow-up despite early initiation of treatment. Thus, watch-and-wait is still regarded the standard for asymptomatic patients. Patients with indolent lymphoma have a significant heterogeneity in terms of tumor burden, symptoms (according to anatomical sites) and the need for instant therapy. Therefore, the initiation of treatment and treatment option should be decided with a clear goal in each patient according to the need for therapy and clinical benefits with the chosen treatment. In this review, we cover the current treatment of follicular lymphoma and marginal zone lymphoma.

Keywords: Indolent lymphoma, Non-Hodgkin’s lymphoma, Follicular lymphoma, Marginal zone lymphoma

Fig 1.

Figure 1.Follicular lymphoma inter-national prognostic index (FLIPI) 1,2 and survival outcomes.
Blood Research 2022; 57: S120-S129https://doi.org/10.5045/br.2022.2022054

Table 1 . Indications for treatment in low grade lymphoma..

IndicationDetail
High tumor burden [10]Any site >7 cm
Three or more sites >3 cm
Splenomegaly (>16 cm)
Pleural or peritoneal effusion
Circulating tumor cells >5,000/mL
Cytopenia secondary to lymphoma
- Absolute neutrophil count <1,000/mL
- Platelet count <100,000/mL
Disease-related symptomsFever
Night sweats
Weight loss
Compression
Other lymphoma-related symptoms
Steady progressionOver at least 6 months

Table 2 . Treatment of follicular lymphoma..

Disease statusTreatmentComment
Localized diseaseRT- Potentially curative (ISRT 24–30Gy)
- The addition of systemic therapy to RT improves PFS but not OS
Rituximab- Radiotherapy ineligible patients
CIT- Non-contiguous, bulky disease
Watch and wait- Stable, asymptomatic patients
Advanced diseaseWatch and wait- Without treatment indications (Table 1)
CIT± antibody maintenance- Rituximab or obinutuzumab+(CHOP, CVP, Bebdamustine)
- Maintenance improves PFS but not OS
Rituximab
Lenalidomide+rituximab
- For low tumor burden
- As effective as chemoimmunotherapy
Relapsed diseaseWatch and wait- Stable, asymptomatic patients
Palliative RT- 2×2Gy
CIT± antibody maintenance- Long previous remission with CIT
- Non-resistant regimen
Rituximab- For low tumor burden
Lenalidomide+rituximab- POD≤24 months after CIT
PI3K inhibitors- Double refractory disease
EZH2 inhibitor (tazemetostat)- EZH2 mutation-positive disease
Radioimmunotherapy- Not widely used
Auto/allo-HSCT- In selected patients
CAR-T cell therapy- After ≥2 lines of systemic therapy [63]

Abbreviations: CAR-T, chimeric antigen receptor T-cell; CIT, chemoimmunotherapy; CR, complete response; EZH2, enhancer of zeste homolog 2; HSCT, hematopoietic stem cell transplantation; ISRT, involved site RT; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PI3K, phosphatidylinositol 3-kinase; POD, progression of disease; RT, radiotherapy..


Table 3 . Treatment of marginal zone lymphoma..

DiseaseTreatmentComment
Gastric ENMZLH. pylori eradication- PPI+clarithromycin+(amoxicillin or metronidazole)
RT- H.pylori(-), or eradication failure
Rituximab- For radiotherapy ineligible patients
Gastrectomy- Major gastric bleeding
Non-gastric ENMZLWatch and wait- Stable asymptomatic disease
Targeting infectious agents- HCV treatment for HCV(+) disease
- Doxycycline for ocular adnexal ENMZL
RT- Definitive or palliative
Rituximab- Higher response in CTx-naïve patients
CIT- R-chlorambucil, R-bendamustine
Lenalidomide+Rituximab- To avoid chemotherapy
Surgery- Mostly for diagnosis (thyroid, breast, intestine, etc.)
Splenic MZLWatch and wait- Stable asymptomatic disease
HCV eradication- For HCV(+) disease
Rituximab- Offer the most risk/benefit ratio [106]
Splenectomy- After rituximab failure
CIT- For symptomatic disseminated disease after rituximab or splenectomy failure
Nodal MZLTreated as guidelines for FL- Studies enrolled solely MZL are rare

Abbreviations: CIT, chemoimmunotherapy; CTx, chemotherapy; ENMZL, extranodal marginal zone lymphoma; HCV, hepatitis C virus; PPI, proton-pump inhibitor; RT, radiotherapy..


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