Indolent non Hodgkin lymphomas

Dr. Rajib BhattacharjeeJunior Resident

IPGMER, Kolkata

WHO classification 2008

Most common types of NHL encountered in clinical practice

types of NHL Incidence DLBCL 33%

Follicular Lymphoma 22%

Marginal Zone Lymphoma 10%

PTCL 10%

SLL/CLL 7%

Mantle cell lymphoma 7%

Types of NHL based on aggressiveness

Low grade Intermediate grade high grade

Follicular lymphoma

Marginal zone lymphoma

SLL/CLL

DLBCL

PTCL

Burkitt’s lymphoma

Lymphoblastic lymphoma

New ticket day… in the OPD…

Our patient enters…. A man in his 60s

•Median age at presentation – 55-65 years

•Males are affected more than females

I started to listen to his clinical history..

He complained of a painless swelling in his neck..

2/3rd of NHL patients present with asymptomatic lymph node swelling (nodal disease)Common in FL,MCL & SLLSites- Neck 70%Groin 60%Axilla 50%

Any extranodal disease…

• I asked him,” Do you have any problem during swallowing or do you get full with little food?”

1/3rd of NHL patients may present with extranodal disease.Common in DLBCL & MZLSite-GIT - 25-35%Waldayers ring – 18-23%

B Symptoms

I asked 3 questions:-1. Did you suffer from fever in the last few

months?2. Have you lost a lot of weight lately?3. Do you change your shirt often due to night

sweats?Then I asked… did you find any cause to these or

were they unexplained?

Exam time..

• Lymph node examination• Head and neck – waldeyer’s ring• Chest – Sternal/2nd ICS percussion Pleural effusion• Abdomen- Organomegally, Lump, Ascites Testes• Skin - Nodules

Investigations ..

Lab investigations• CBC, KFT, LFT, Electrolytes• Ca2+

• LDH, Uric acid• HBsAg, IgM HBc• HIV I & II

Imaging• Chest X-Ray• CT Thorax, abdomen & pelvis• PET CT• Tc-99m Bone Scan• MUGA/ Echocardiography

Endoscopy • Upper GI

• Bone marrow biopsy A must for all NHL patients (SLL, mantle cell lymphoma – 70% FL – 50% , DLBCL – 15%)

• CSF Cytology Only in suspected leptomeningeal

involvement

Histopathological examination

The cervical lymph node must go for biopsy….

A medium sized accessible lymph node is preferred for excision.Cervical lymph node if palpable, is preffered

Which stage is the disease..???

X = Bulky disease• Clinically diameter > 10cm• CXR PA- Mediastinal mass ratio(MMR) = Max width of mass__ > 0.33

Max intrathoracic dia = Max width of mass >0.35 Intrathoracic dia @ T5 - T6

Possible histologies for our discussion

Follicular Lymphoma

5Y OS

70.7%

50.9%

35.5%

How do I treat this patient if he has localised FL – Stage I & II?

Gr 1-2, non bulky, asymptomatic

IFRT (30Gy)

Gr 3, bulky, B symptoms

IFRT(30Gy) RCHOP (4 cycles)

Boost (upto 40 Gy) IFRT to the bulky site (30Gy)

How do I treat this patient if he has advanced FL – Stage III & IV?

Asymptomatic

Observation or Rituximab

Symptomatic, B symptoms, cytopenias, compromised end organ function

RCVP/RCHOP (6 cycles)

Gr 3 RCHOP (6 cycles)

Important studies study Conclusion

BNLI Study 2003 Observation is a good initial approach in asymptomatic stage III & IV FL

GLSG Trial 2005 & Marcus et al Rituximab with both CVP & CHOP produce enhanced OS

SWOG Trial Anthracyclins fail to improve OS in indolent lymphoma

Bendamustine in 1st line

indolent/mantle cell

R-B R R-CHOP 69.5mo PFS 31.2mo

toxicity

Maintenance Rituximab

Follicular lymphoma RCHOP/RCVP/RFCM

mRituximab R Obv

75% PFS 58%

72% CR 52%

Progressive disease

• Elderly, asymptomatic – Obv• 2nd line chemotherapy – Bendamustine FCM• Radioimmunotherapy – Zavaline, Baxxar• mTOR inhibitors – NVP-BEZ235• Proteasome inhibitors• Stem cell transplant

Marginal zone lymphoma

Three entities• Nodal • Extranodal - MALToma• Splenic

StomachSmall intestineOccularSkinParotidThyroid

How to treat…Extranodal disease• Symptomatic local tumor – RT• Generalized disease Asymptomatic – Obv Symptomatic - CT (Chlorambucil)

Nodal disease – R-CHOP

Splenic disease – Splenectomy or Splenic RT

Gastric MALToma• C/F- abdominal fullness, loss of appetite,

waight loss, B symptoms, pain, bleeding• Diagnosis- Endoscopic biopsy• H. pylori association in 92% (# Isaacson et al)• Antibiotics and PPI (even in H.pylori –ve cases) CRR-75% 5Y FFS-50% OS>90%• Endoscopy after 3 months• Lymphoma persist- *deep invasion *t(11:18)• Antibiotic failure T/t – RT(24-30Gy)• Not suitable for RT – Rituximab monotherapy

SLL

• Localized disease – IFRT (30Gy)

• Advanced disease – Chemoimmunotherapy

Age>70, co-morbidities Age<70, medically fit Relapse

•Obinutuzumab + Chlorambucil•Rituximab + Chlorambucil•Bendamustine + Rituximab

•FCR (Fludarabine + Cyclofosfamide + Rituximib)

•Ibrutinib

IFRT

Fallow up

• Physical exam & labwork - 3-6 months for 1st 5 years then annually.

• CT scan every 6 months for 2 years then annually.

THANK YOU