TION OF HEMATOLOGY

Indolent Lymphoma
DIDACTICS
Andrea Reyes
TION OF HEMATOLOGY

Learning Objectives
• To discuss an overview on the diagnosis and manifestations of iNHL
• To present different types of iNHL
• To discuss treatment options
• To discuss targeted therapy in indolent lymphoma
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Indolent Lymphomas
• Mature B-Cell neoplasms with a tendency of slow progression
• Generally account for 35-40% of Non-Hodgkin Lymphoma
• Heterogenous disease with less aggressive presentation
• Frequent relapses (consider incurable)

Duffles, G., Delamain, M. T., & De Souza, C. A. (2021). Current therapy for indolent lymphomas. Hematology,
Transfusion and Cell Therapy, 43. https://doi.org/10.1016/j.htct.2021.11.003
TION OF HEMATOLOGY

Indolent Lymphomas
• Disseminated Lymphomas/Leukemias
• CLL
• Hairy Cell Leukemia
• Lymphoplasmacytic Lymphoma
• Splenic Marginal Zone B cell Lymphoma
• Nodal Lymphomas
• Follicular Lymphoma
• Nodal marginal zone B lymphoma
• Small lymphocytic lymphoma
• Nodular lymphocyte predominant Hodgkin Lymphoma
• Extranodal Lymphomas
• Extranodal marginal zone B cell lymphoma of mucosal associated lymphoid tissue

Kaushansky, K. (2021). Williams hematology, 10th edition. McGraw-Hill Education.

TION OF HEMATOLOGY

Treatment by cancer type. NCCN. (n.d.). Retrieved October 4, 2022, from

https://www.nccn.org/guidelines/category_1
TION OF HEMATOLOGY

Follicular Lymphoma Clinical Manifestations

Elderly (Median Age 60 years old)
Slight Female Predominance M:F 1:1.7
• Most common indolent lymphoma Painless Lymphadenopathy
• Pathology BM involvement common (70%)
• Derived from germinal B-cells with
Risk Factors
Mixture of centrocytes and
centroblasts Heavy Smoking
Pesticides
• Exhibits a nodular or follicular
T(14,18)
histologic pattern
• Hallmark: t(14,18) (q32,q31) Immunophenotyping
Negative: CD 5 (-), CD43(-), Cyclin D1 (-)
• Rearrangement of BCL2 gene 
overexpression of antiapoptotic Positive: CD 10 (+) BCL6 (+) BCL2 (+)
protein B-Cell: CD20 (+) CD19(+)

Duffles, G., Delamain, M. T., & De Souza, C. A. (2021). Current therapy for indolent lymphomas. Hematology,
Transfusion and Cell Therapy, 43. https://doi.org/10.1016/j.htct.2021.11.003
TION OF HEMATOLOGY

Follicular Lymphoma
Morphology

• Grade 1 0-5 centroblast

Grade 1 Grade 3A
• Grade 2 6-15 centroblast
• Grade 3 >15 centroblast
• 3A some small centrocytes
• 3B solid sheets of centroblasts --
no centrocytes
Grade 2 Grade 3B
• Pattern of evolution is
indistinguishable between 1-3A
• 50% treatment free at 3 years
• 3B requires DLBCL management
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Follicular Lymphoma
Prognosis

Score 5 Year OS
Low (0-1) 91%
Intermediate (2) 60-78%
High (≥3) 51-52%
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Follicular Lymphoma
Treatment

Three Clinical Situations Groupe d’Etude Lymphomes Folliculaires (GELF) Criteria

Presence of at least one of the ff defines a patient with high tumor burden
• Patients with localized disease Lymphoma tumor ≥ 7 cm
Three nodes in 3 distinct areas with each node ≥ 3 cm
• Patients with disseminated disease Presence of systemic symptoms (B Symptoms)
but low tumor burden Symptomatic Splenomegaly
Ascites/Pleural Effusion
• Patients with clear indication for Cytopenias (ANC <1000, Platelet <100k)
systemic treatment or high tumor Leukemia (>5000/malignant cells)
burden

Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
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Follicular Lymphoma
Localized Disease

Stage 1 or Contiguous Stage 2 Disease (Localized Disease)

• Involved Site Radiotherapy (35-40 gy)
• Chemotherapy + RT for longer progression free survival

Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

Follicular Lymphoma
Low Tumor Burden

Disseminated Disease with Low Tumor Burden / Asymptomatic

• Watchful waiting remains standard course
• Rituximab single agent has been popular due to increase in PFS after 4 infusions
Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

Follicular Lymphoma
High Tumor Burden
High tumor burden/indication for treatment
• Combination with rituximab/obinutuzumab (Bendamustine, CHOP, CVP)

First Line Therapy First Line Therapy For Elderly/Infirm

Bendamustine + Obinutuzumab/Rituximab Rituximab 375mg/m2 weekly for 4
CHOP + Obinutuzumab/Rituximab doses
CVP + Obinutuzumab/Rituximab
Lenalidomide + Rituximab

Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

Follicular Lymphoma
Consolidation Therapy

• After CR/PR, some would consider consolidation or extended therapy

especially in high tumor burden patients
• Regimens
• Rituximab maintenance 375mg/m2 every 12 weeks for 2 years
• Obinutuzumab maintenance for rituximab refractory disease
• 1gram every 7 weeks for 12 doses

Treatment by cancer type. NCCN. (n.d.). Retrieved October 4, 2022, from

https://www.nccn.org/guidelines/category_1
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Follicular Lymphoma
Second line therapy

• Use alternative regimen combined with anti-CD20

• Rituximab maintenance may be given to rituximab naïve prior or r/r disease (every 3 months for 2 years)
• ASCT has durable response for r/r follicular lymphoma esp in early relapses
Early relapse is relapse within 24 mos = poorer prognosis
Salles, G.• (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

Follicular Lymphoma:
Progressive Disease/ Histologic Transformation (HT)

• Progressive Disease
• Anti CD-19 CART cell therapy
• PI3K inhibitor (Copanlisib), EZH2 inhibitor (Tazemetostat)
• ASCT on first relapse
• HT with no prior therapy
• If double hit  treat as high grade; if not RCHOP/DA-EPOCH
• HT after multiple therapies
• Clinical Trial, CART Cell
• Chemotherapy (RCHOP, DHA, ICE)
• Once CR/PR for alloHSCT
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Treatment by cancer type. NCCN. (n.d.). Retrieved October 4, 2022, from

https://www.nccn.org/guidelines/category_1
TION OF HEMATOLOGY

Hairy Cell Leukemia Clinical Features

Fatigue, Infections
Splenomegaly, Cytopenias
Mean Age 55 years old, some 20-30s
• Adult chronic B-Cell Leukemia Male Predominance 4:1
• Cell of origin in uncertain  late activated
memory B cell with mutation Cytogenetics
• infiltrating marrow, spleen liver Negative: CD5 (-), CD 10(-)
• Hypermutated Immunoglobulin genes Positive: CD103(+), CD 25(+), CD11c(+)
• Most common mutation: B: CD19(+), CD20(+)

• BRAF V600E in almost 100% of patients

• Activates MEK/ERK  proliferation Risk Factors
• Survival Improved due to Purine Insecticides/Pesticides
Ionizing Radiation
Nucleoside Analogues
• 90% at five year follow-up
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Hairy Cell Leukemia

Asymptomatic
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Hairy Cell Leukemia

Symptomatic

First Line Therapy

Claridibine+Rituximab
Pentostatin
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Lymphoplasmacytic Lymphoma/WM
Treatment Response

Complete Response Normalization of blood counts; Hb>11g/dL; Platelet > 100k; ANC >1000
Regression of Splenomegaly; Absence of HCL in BM
Timing BMA be done after 4 months of therapy if given cladribine
Partial Response Near Normalization of blood count with 50% improvement of organomegaly and
BM biopsy
Stable Disease Not met criteria for remission
Progressive Disease Increase in symptoms; 25% increase in organomegaly; 25% decline in
hematologic parameters
Relapse Reappearance of HCL in Peripheral Blood, BM or both; Hematologic Relapse –
cytopenia below threshold; No treatment for morphologic relapse
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Hairy Cell Leukemia

Relapsed/Refractory/Progressive Disease

• Relapse <2 years

• Clinical Trial
• Vemurafenib + Rituximab
• Relapse 2 years
• Retreat with initial purine
analogue + rituximab
• Progressive/Refractory
• Clinical Trial
• Moxetumomab
• Ibrutinib (off label)
TION OF HEMATOLOGY

Treatment by cancer type. NCCN. (n.d.). Retrieved October 4, 2022, from

https://www.nccn.org/guidelines/category_1
TION OF HEMATOLOGY

Marginal Zone Lymphoma (MZL)

• GC: In the dark zone
Centroblasts proliferate
and undergo somatic
mutations; In the light
zone, centrocytes
undergo class-switch
recombination  FL,
BL, DLBCL
• MZL arise from B cells
located in marginal zone
of lymphoid follicles
Fernández-Serrano, M., Winkler, R., Santos, J. C., Le Pannérer, M.-M., Buschbeck, M., &amp; Roué, G. (2021). Histone
modifications and their targeting in lymphoid malignancies. International Journal of Molecular Sciences, 23(1), 253.
TION OF HEMATOLOGY

Marginal Zone Lymphoma Clinical Manifestations

Middle Age
Painless Lymphadenopathy
• 10% of all NHL Splenomegaly
• 3 Types Hemolytic Anemia or ITP (10-15)
• Extranodal MZL (MALT Lymphoma)
• 70% of cases Immunophenotyping
• Most common site GI (50%) Negative: CD 5 (-), CD10(-), CD103(-)
• Splenic MZL B-Cell: CD20 (+), CD19(+) CD22(+)
• 20% of cases
• Nodal MZL Risk Factors
• Least common Develop in chronic immune stimulation
Cytogenetics: t(11,18), t(14,18), t(1,14),
t(3,14)

Duffles, G., Delamain, M. T., & De Souza, C. A. (2021). Current therapy for indolent lymphomas. Hematology,
Transfusion and Cell Therapy, 43. https://doi.org/10.1016/j.htct.2021.11.003
TION OF HEMATOLOGY

Marginal Zone Lymphoma

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Extranodal MZL:
MALT Lymphoma
Clinical Features
• Arises in organs with an anatomically well- Symptoms in site involved; BM uncommon
defined MALT GI MALT: dyspepsia, epigastric pain, nausea
• GI, Nasopharynx, Lung
Ocular: proptosis, edema
• H. Pylori has been the etiologic agent in 90% of Cutaneous: papules, plaques, nodules
patients with gastric MALT Lymphoma
• Biopsy is required for diagnosis
• Most common: t(11,18)(q21,q21) Risk Factors
• t(14,18)(q23,q21) Develop in chronic immune stimulation
• t(1,14)(p22,q32) Microbial Species: H pylori, C. jejuni, H.
• T(3,14)(p13,q32) heilmannii, Borrelia, Chlamydophilia
• Favorable Prognosis Autoimmune disease: Thyroiditis, Sjogren
syndrome
• 15% would relapse in 3 years
• Histologic transformation in 10%
TION OF HEMATOLOGY

Extranodal MZL: Gastric MALT Lymphoma

Staging

Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

Extranodal MZL: Gastric MALT Lymphoma

Localized

3 MONTH FFUP:
Restage with endoscopy/biopsy
- If CR, ffup every 3-6 mo for 5 years
- If still with lymphoma, ISRT
- If still H pylori, second line Abx

RECURRENCE/ PROGRESSIVE DISEASE/ RELAPSE

- Indication for treatment

All H. pylori positive gastric MALT should be given H. pylori therapy

- Induce remission and control in 50% of patients; confirm eradication after 6 wks
If t(11,18) positive  ISRT 30 Gy or rituximab(second line)
Gastrectomy should be first line in cases of life threatening hemorrhage, perforation, pyloric stenosis
Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

Extranodal MZL: Gastric MALT Lymphoma

Symptomatic

First Line Therapy Second Line Therapy

Bendamustine + Rituximab BTK Inhibitors; Lena+Rtixumab
RCHOP Bendamustine+Obinutuzumab

First Line Therapy For Elderly/Infirm Second Line Therapy in Elderly

Rituximab 375mg/m2 weekly for 4 doses BTK; Rituximab weekly

Consolidation Second Line Consolidation

Rituximab 375mg/m2 every 8-12 weeks for 2 Obinutuzumab 1g every 8 wks 12doses
years HSCT

Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

Extranodal MZL: NonGastric MALT

Lymphoma

Any organ with well structured MALT (orbital, nasopharynx, lung)

Locoregional treatment (surgery and RT) mainstay in localized disease
Rituximab as second line or cutaneous MZL
Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

Extranodal MZL: NonGastric MALT

Lymphoma
First Line Therapy
Bendamustine + Rituximab
RCHOP

First Line Therapy For Elderly/Infirm

Rituximab 375mg/m2 weekly for 4 doses

Consolidation
Rituximab 375mg/m2 every 8-12 weeks for 2
years

If with any indication for treatment on follow-up, treat as MZL

Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

Marginal Zone Lymphomas

TION OF HEMATOLOGY
MZL: Splenic MZL
• 20% of MZL
• Pathology: arises from post GC
involves white pulp of spleen
• Associated with
• Chronic HCV Infection
• Most common cytogenetics: complete
or partial 3q trisomy (39%)
• Most frequent mutation: NOTCH2 gain
of function
Clinical Features
Male preponderance
Median Age: 65 years old
Asymptomatic Splenomegaly
Cytopenia; AIHA/ITP (10%)
Cytogenetics
Negative: CD5 (-), CD 10(-), CD23 (-)
Positive: IgD, IgM, CD44(+), CD49(+),
CD29(+)
B: CD20(+), CD 21(+), CD19
Risk Factors
Chronic HCV infection
Autoimmune
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MZL: Splenic MZL

Asymptomatic

Asymptomatic patients followed clinically, treatment does not influence

survival
Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

MZL: Splenic MZL

Symptomatic

Symptoms:
Pain, Early Satiety
Hb <10
Platlelet <80k
ANC <1000

Single agent rituximab may be useful.

Splenectomy is considered for massive and symptomatic splenomegaly
Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

MZL: Splenic MZL

Recurrence

First Line Therapy

Bendamustine + Rituximab
RCHOP

First Line Therapy For Elderly/Infirm

Rituximab 375mg/m2 weekly for 4 doses

Consolidation
Rituximab 375mg/m2 every 8-12 weeks for 2
years

Salles, G. (2020). How do I sequence therapy for follicular lymphoma? Hematology, 2020(1), 287–294.
https://doi.org/10.1182/hematology.2020000156
TION OF HEMATOLOGY

Marginal Zone Lymphomas

TION OF HEMATOLOGY

MZL: Nodal MZL

Clinical Features
• Least common (<2%) Median Age: 50-60
• Pathology: not clear BM involvement in half
Disseminated peripheral and abdominal
• Associated weakly with nodal involvement
• Autoimmunity
• No typical cytogenetic aberrations
• Response to treatment is good using Risk Factors

FL and NHL paradigms Autoimmune

• Treat like FL
• High Tendency to relapse
TION OF HEMATOLOGY

Treatment by cancer type. NCCN. (n.d.). Retrieved October 4, 2022, from

https://www.nccn.org/guidelines/category_1
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma
Waldenstrom Macroglobulinemia
WHO Criteria of LPL
• Uncommon mature B cell Neoplasm of small B lymphocytes, plasmacytoid lymph, plasma cells
lymphoma Involves BM sometimes spleen
Doesn’t fulfill any other B-cell lymphoid neoplasm
• Accumulation of clonal
immunoglobulin M secreting WHO Criteria of WM
lymphoplasmacytic cells LPL with bone marrow involvement and IgM gammopathy
• Male predominance
WM International Workshop Criteria
• Increase incidence with age
IgM gammopathy
• Risk Factor: Genetics BM infiltration
• First degree family members Diffuse interstitial pattern of BM infiltration
Increased risk by 20% Immunophenotyping: CD19, CD20 sIgM

Duffles, G., Delamain, M. T., & De Souza, C. A. (2021). Current therapy for indolent lymphomas. Hematology,
Transfusion and Cell Therapy, 43. https://doi.org/10.1016/j.htct.2021.11.003
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM
Pathogenesis not clearly understood: post GC cell  hypermutation but not class switch
Common Mutations:
• MYD88: highly recurrent mutation
• 90% of WM; absent in myeloma
• Role as adaptor molecule in TLR and IL-1R signaling
• CXCR4:
• 30% of WM, 2 types: non-sense or frameshift
• C-terminus of CXCR4 receptor; impacts serine phosphorylation sites
Cytogenetics:
• Del in 6q21: 40-60% in WM patients = poor prognosis
• trisomy 4 = poor prognosis
• Others: trisomy8, 13q del, 17p del, 11q del
Marrow Environment:
• Enhanced CD40-CD40L interaction in WM  survival and growth
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Lymphoplasmacytic Lymphoma/WM

Signaling Pathways Driven

by MYD88
✗
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Lymphoplasmacytic Lymphoma/WM
CXCR4 C-tail Mutations
• Warts, Hypogammaglobulinemia,
Infection
• 30-40% of WM patients
• >30 nonsense/frameshift
• Silencing of TLR pathway regulators
• Promote stromal derived factor 1
SDF-1 hyperactivation, WM cell
growth and ibrutinib resistance by
AKT/ERK signaling
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM
Laboratory Findings
Immunophenotyping
Negative: CD 5 (-), CD43(-), Cyclin D1 (-)
Positive: CD 138 (+) CD38 (+)
B-Cell: CD20 (+) CD19 (+) CD22 (+)

Gammopathy if WM
Morphology Findings
Secretes monoclonal IgM
• PBS: Rouleax Formation seen d/t If IgM spike >4g/dL, test for serum viscosity
IgM accumulation
• BMA: infiltrates of lymphocytes,
plasma cells; mast cells common
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM
CLINICAL FEATURES
• Male, Elderly
• Weakness and fatigue - most common
• B-symptoms (25%)
• Lymphadenopathy, hepatosplenomegaly (25%)
• Morbidity due to tissue infiltration by cells and
IgM activity
• Funduscopic abnormalities (34%)
• Hyperviscosity syndromes
• Cryoglobulinemia
• Neuropathies (22%)
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Waldenstrom Macroglobulinemia
Morbidity Mediated by Immunoglobulin M

Hyperviscosity
• Due to increase in resistance to blood flow
• High concentration of IgM form aggregates and bind to water
• Serum Viscosity is proportional to IgM concentration upto 30g/L then
increases sharply
• IgM interact with blood cells  Increase viscosity decreases EPO 
anemia
• Symptoms occur when monoclonal IgM >50g/L
• Oronasal mucosal bleed, visual disturbance
• Inappropriate red cell transfusion can exacerbate hyperviscosity
TION OF HEMATOLOGY

Waldenstrom Macroglobulinemia
Morbidity Mediated by Immunoglobulin M

Cryoglobulinemia
• Type 1: monoclonal IgM
• Type 2: Mixed Cryoglobulins: IgM-IgG
complexes
• Cryoprecipitation depends on
concentration
• Symptoms are from impaired blood
flow in small vessels
• Raynaud phenomenon,
acrocyanosis and necrosis to
regions exposed to cold
TION OF HEMATOLOGY

Waldenstrom Macroglobulinemia
Morbidity Mediated by Immunoglobulin M

Autoantibody
• Monoclonal IgM exerts its pathogenic effects through recognition of
autologous antigens  nerve constituents, rbc antigens
TION OF HEMATOLOGY

Waldenstrom Macroglobulinemia
Morbidity Mediated by Immunoglobulin M

Neuropathy
• 5-40% of patients
• Due to IgM antibody activity toward nerve constituents, endoneurial
deposits to IgM, tubular deposits in endoneurium by cryoglobulin,
amyloid deposits in nerve structure
• Half of patients: Anti-myelin associated glycoprotein (Anti-MAG)
• Distal symmetrical, slow progressive
TION OF HEMATOLOGY

Waldenstrom Macroglobulinemia
Morbidity Mediated by Immunoglobulin M

Cold Agglutinin Hemolytic Anemia

• Monoclonal IgM may have cold agglutinin activity
• Less than 10% of WM
• Cold Agglutinin titers 1:1000
• IgM kappa light chain reacts with RBC I/i antigens  complement
activation
• Hemolysis is extravascular
• Hgb is usually above 70g/L
TION OF HEMATOLOGY

Waldenstrom Macroglobulinemia
Morbidity Mediated by Immunoglobulin M

IgM Tissue Deposition

• Linear deposition in skin basement membrane  bullous skin disease
• Deposits in dermis  papules on extensor surface
• Deposits in lamina propria of intestine  malabsorption, GI Bleed
• Deposits in Kidney  less common/less severe  less light chain
excretion
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Lymphoplasmacytic Lymphoma/WM
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM

Low <0.535

awmrisk.com

High >1.802
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM

First Line Therapy Previously Treated

Bendamustine + Rituximab Bendamustine + Rituximab
Bortezomib/Dexamethasone/Rituximab Bortezomib/Dexamethasone/Rituximab
Ibrutinib/Rituximab Ibrutinib/Rituximab
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM
Frontline Therapy

BR: Bendamustine+Rituximab
BDR: Bortezomib/Dexamethasone/Rituximab
DRC: Dexamethasone/Rituximab/Cyclophosphamide

Broccoli, A., &amp; Zinzani, P. L. (2020). How do we sequence therapy for marginal zone lymphomas? Hematology,
2020(1), 295–305. https://doi.org/10.1182/hematology.2020000157
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM
Frontline Therapy
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM
Relapse After First Line Treatment

Broccoli, A., &amp; Zinzani, P. L. (2020). How do we sequence therapy for marginal zone lymphomas? Hematology,
2020(1), 295–305. https://doi.org/10.1182/hematology.2020000157
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM
HSCT

• For relapsed or refractory patients

• Disease resistant to chemotherapy and number of lines of therapy
were the most important prognostic factors for PFS and OS
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM
Treatment Response

Complete Response IgM in normal range; disappearance of monoclonal protein; absence of BM

involvement, resolution of adenopathy, no signs or symptoms
Very Good Partial Response 90% reduction in IgM, decrease in adenopathy on CT Scan; no new symptoms or
active disease
Partial Response 0% reduction in IgM, decrease in adenopathy on CT Scan; no new symptoms or
active disease
Minor Response 25% reduction in IgM; no new symptoms or active disease
Stable Disease <25% reduction/increase in serum IgM, no progression adenopathy/cytopenias,
no significant symptoms
Progressive Disease 25% increase in IgM; progression of clinically significant findings/symptoms, 10%
body weight loss

Rituximab induces a spike/flare in serum IgM levels

usually when used as monotherapy or in combination, can
last for several weeks to months --> SKEWING Treatment
Response; BMB consider to clarify
TION OF HEMATOLOGY

Lymphoplasmacytic Lymphoma/WM
Prognosis
REVISED IPSS WM SCORING SYSTEM TOTAL SCORE 5 YEAR OS
AT INITIAL TX
Age > 65 1 point 0-1 points (except age) 87%
Hgb < 11.5 g/dL 1 point 2 points or age >65 68%
B2M >3mg/L 1 point 3-5 points 36%
IgM > 7g/DL 1 point
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Updates
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SEPT 2022
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Bispecific to both
CD20 and CD3
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Showing Good
Durability in Indolent
Lymphomas
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Population 20 MZL, 33 FL Zanubrutinib is second generation BTK inhibitor

Exposure Zanubrutinib
Zanubrutinib monotherapy has a favorable benefit risk profile in patients with
Outcome Overall Response Rate relapsed/refractory indolent NHL
Method Open-label multicenter
Prospective Study In MZL patients ORR 80% CR20%
In FL patients ORR 36.4% CR 18.2 median PFS 10.4months
Follow-up 33.8 months
Treatment tolerated well. Most adverse events < grade 2 (Diarrhea, Rash)
Grade 3 AE (Bleeding, Neutropenia, Thrombocytopenia)
TION OF HEMATOLOGY

Indolent Lymphoma
DIDACTICS
Andrea Reyes
TION OF HEMATOLOGY

Response Criteria for NHL

PET SCAN CT SCAN
Complete Score 1-3 with/without mass; No new Target nodes decrease 1.5cm in long
Response lesions; No FDG Avid Marrow transverse diameter; no extralymphatic
disease; normal by morpho in BMA; flow neg
Partial Response Score 4-5 with reduced uptake; BM Residual 50% decrease in SPD up to 6 target
uptake higher than update but reduced measurable nodes and extranodal sites;
compared with baseline assign 5x5mm as default
Stable Disease Score 4-5 with no significant change in FDG <50% decrease from baseline SPD of up to 6
uptake from baseline at interim. No new dominant measurable nodes
lesions
Progressive Score 4-5 with increase in intensity of uptake Longest transverse diameter >1.5cm and
Disease from baseline; New FDG avid foci consistent increase 50% from Transverse/Perpendicular
with lymphoma Diameter; Increase in splenic length by 50%;
New/Recurrent involvement