Lymphoma and MM

Question 1

What is Lymphoma?

Malignant transformation of lymphocytes
◦ Solid tumors of the immune system

2 major types of lymphomas
◦ Hodgkin lymphoma (HL): characterized by ___ cells
◦ Non-Hodgkin lymphoma (NHL)
◦ 30 + unique histopathologic diseases
◦ Varied clinical course between subtypes
◦ 90% are ___ -cell

Chemotherapy backbone of treatment

Many subtypes are curable

Answer 1

• Reed-Sternberg
• B

Question 2

HL – Epidemiology

if untreated 90% fatal within 2 to 3 years
Median age at diagnosis: ___
bimodal

Answer 2

39

Question 3

HL – Pathophysiology

HL – Pathophysiology ___ cells: multinucleated giant cells, originate from B-lymphocytes

B-cell transcription disrupted
◦ Loss of immunoglobulin expression
◦ Lack of apoptosis pathways
◦ Proliferation of malignant cells

Risk Factors
- viral exposure
- impared immune function
- genetic factors

Answer 3

Reed-Sternberg

Question 4

HL - Presentation

Painless, rubbery, enlarged lymph
node

B symptoms (25-50% of patients)
◦ Fever (greater than 38 C)
◦ Drenching ___ , especially at night
◦ Unintentional weight loss of greater than ___% in < 6 months

Pruritus

Answer 4

sweats
10

Question 5

HL - Diagnosis

___ is the gold standard

Answer 5

Excisional biopsy

Question 6

Staging - Classification

Early-stage favorable
* Stage I-II without unfavorable factors

Early-stage unfavorable
* Stage I-II with unfavorable factors

Advanced-stage
* Stage III-IV

Answer 6

Unfavorable Factors:
* Large mediastinal
adenopathy
* Multiple involve nodal
regions
* B symptoms
* Extranodal involvement
* Significantly elevated
erythrocyte sedimentation
rate (ESR)

Question 7

HL - Treatment

Goal: ___ while minimizing toxicities and long-term
complications

Modalities
◦ Combination chemotherapy
◦ ABVD
◦ Stanford V
◦ BEACOPP
◦ AAVD
◦ Radiation
◦ Autologous stem cell transplant

Answer 7

CURE

Question 8

Treatment by Stage

IA, IIA Favorable

Answer 8

• ABVD + RT
• Stanford V + RT
• ABVD
• ABVD + escalated
• BEACOPP

Question 9

Treatment by Stage

Stage I-II
Unfavorable

Answer 9

• ABVD + RT
• Stanford V + RT
• Escalated BEACOPP x 2 + ABVD x 2 + RT

Question 10

Treatment by Stage

Stage III/IV

Answer 10

• ABVD ± RT
• AAVD
• Stanford V + RT
• Escalated BEACOPP ± RT (IPS > 3)

Question 11

ABVD

Answer 11

• doxorubicin
• bleomycin
• vinblastine
• dacarbazine

cardio and pulm toxicity

Question 12

ABVD

high amount of neutropenia
low amount of infecction

Answer 12

we dont know why

Question 13

AAVD

Answer 13

• doxorubicin
• brentuximab vendotin
• vinblastine
• dacarbazine

Question 14

Relapsed HL

• High dose chemotherapy with ____ stem cell rescue
• Maintenance therapy if high risk of relapse with brentuximab vedotin following stem cell transplant

Answer 14

autologous

Question 15

HL summary

Early stage disease
◦ Involved-field radiation
◦ 2-4 cycles of ___ chemotherapy

Answer 15

ABVD

Question 16

HL summary

Advanced stage disease
◦ 6-8 cycles of ___ or ___ chemotherapy
◦ ___ preferred in younger patients with Stage III or IV

Answer 16

• ABVD, AAVD
• AAVD

Question 17

HL summary

Relapsed disease
◦ High-dose chemotherapy followed by ___ cell rescue

Maintenance therapy (high risk disease post transplant)
◦ ___

Answer 17

• stem
• Brentuximab vedotin

Question 18

Non Hodgkin Lymphoma (NHL)- epidemiology

Median age at diagnosis: ___
5-year survival rate: 74.3%

Answer 18

68

Question 19

NHL – Pathophysiology

Malignant __ or ___ lymphocytes and ___

Malignant cells proliferate and replace normal cells in the lymph nodes and/or bone marrow

Answer 19

B
T
precursors

Question 20

NHL – Presentation

Presentation depends on tumor location
◦ B-cell: lymph nodes, spleen, bone marrow
◦ T-cell: extra nodal sites (skin and lungs)

B symptoms (3)

Diagnosis: ___ biopsy is best

Answer 20

• Fever (greater than 38oC)
• Drenching sweats, especially at night
• Unintentional weight loss
  of greater than 10 % in < 6 months
• excisional

Question 21

NHL: B-Cell Lymphomas

Indolent (25-40%)
- Relatively ___ survival
- Usually ___
- Follicular (Grade 1 or 2)
* Marginal zone
* Small lymphocytic lymphoma

Answer 21

• long
• incurable

Question 22

NHL: B-Cell Lymphomas

Aggressive (60-75%)
- Rapid growth
- ___ survival if untreated
- Usually ___
- Follicular (Grade 3)
- ___ (DLBCL)

Answer 22

short
curable
Diffuse large B-cell

Question 23

NHL: B-Cell Lymphomas

Highly Aggressive
- Doubling time = 18 hours
- Usually ___
- Burkitt’s
- Lymphoblastic
- AIDS-related

Answer 23

curable

Question 24

NHL – Treatment Approaches

Answer 24

Treatment depends on subtype, staging, and patient factors

Question 25

# Follicular Lymphoma Treated if symptomatic or patient preference 2nd most common type of NHL - Low grade is not “curable,” so only treat when needed Indolent: Grade 1 and 2, Median age: 60, Median survival: 8 to 10 years

Answer 25

Richter’s Transformation - Follicular lymphoma can transform into an aggressive NHL!! - Chemotherapy yields 40% CR (of the DLBCL) but: Still have underlying follicular lymphoma

Question 26

# Diffuse Large B-Cell Lymphoma (DLBCL) 30% of NHL Median age of diagnosis: ___ 30 to 40 % present with extranodal disease: ◦ Head/neck, GI tract, Skin, Bone, Testes, CNS

Answer 26

70

Question 27

# NHL Multi-Agent Chemotherapy R-CHOP

Answer 27

- rituximab - cyclophosphamide - doxorubicin - vincristine - prednisone

Question 28

# NHL Multi-Agent Chemotherapy DA-EPOCH + rituximab

Answer 28

- Etoposide 50 - Prednisone 60 - Vincristine 0.4 - Doxorubicin 10 - Cyclophosphamide - rituximab *Dose-adjustment paradigm based on twice weekly CBC (nadir ANC count

Question 29

# NHL Multi-Agent Chemotherapy Pola + R+ CHP

Answer 29

Polatuzumab vedotin Rituximab Cyclophosphamide Doxorubicin Prednisone

Question 30

# DLBCL Treatment - ___ and ___ mostly

Answer 30

R-CHOP Pola - R -CHP

Question 31

# NHL – Rituximab and Hepatitis B Hepatis B viral ___ seen in patients receiving anti-CD20 monoclonal antibody-based therapy - Hepatitis B ___ antigen (HBsAg) and hepatitis B ___ antibody (HBcAb) prior to anti-CD20 directed therapy Treatment with pre-emptive therapy: ___ 0.5 mg daily

Answer 31

- reactivation - surface - core - entecavir

Question 32

# Anti-CD20 antibody late neutropenia Occurs in approximately 20% of patients Onset is delayed, weeks to months after last exposure to CD20 monoclonal antibody therapy Can be severe, but generally do not present with infections Treatment: ___ (G-CSF) ◦ Intravenous immunoglobulins (IVIG) for refractory

Answer 32

gram colony stimulating factors

Question 33

# Relapsed DLBCL/Aggressive NHL ___ intent - ___ chemotherapy followed by ___ stem cell rescue - Chimeric Antigen Receptor (CAR) T-cell therapy Palliative chemotherapy - Bendamustine + Rituximab + Polatuzumab Bispecific T-cell Engagers ◦ Epcoritamab ◦ Glofitamab

Answer 33

Curative - salvage, autologous

Question 34

# CAR T-cell in NHL 3 drugs all target ___

Answer 34

CD19 - Tisagenlecleucel - Axicabtagene ciloleucel - Lisocabtagene maraleucel

Question 35

# Bispecific T-cell Engagers Third line option ◦ After at least 2 lines of systemic therapy ◦ Includes patients who progressed after CAR-T or stem cell transplant Epcoritamab and glofitamab ◦ Receptor for CD3 on T-cell and ___ on B-Cells Mechanism: ◦ Activation of T-cell = proinflammatory cytoxine release = B-cell lysis

Answer 35

makes T cell and cancer hold hands

Question 36

# Bi-Specific T-Cell Engager & CAR T-cell Unique Toxicities Cytokine Release Syndrome (CRS) - Cytokines are released when CAR T cells bind to their target antigen or T cells activated by binding to receptor and cause cancer cells destruction. **Turns ___ the immune system** Treatment is emergent! ◦ Tocilizumab: anti-interleukin-6 (IL-6) (grade 2 or higher) ◦ Does not have impact on the efficacy of CAR-T-cell therapy ◦ Corticosteroids (grade 3 or higher) ◦ ___ T-cell function

Answer 36

- on - impairs

Question 37

# Bi-Specific T-Cell Engager & CAR T-cell Unique Toxicities Immune Effector Cell Associated Neurotoxicity Syndrome (ICANS) - Specific neurological assessments needed = immune effector cell encephalopathy (ICE) scores, which include hand writing - Underlying mechanism is not fully understood - Treatment must be with ___

Answer 37

corticosteroids

Question 38

# Lymphoma Summary Most common hematologic malignancy 2 types: ◦ Hodgkin lymphoma ◦ Non-Hodgkin lymphoma Treatment with multi-agent chemotherapy ◦ HL: ___ ◦ NHL: ___ 5-year overall survival is greater than 70%

Answer 38

- ABVD - R-CHOP

Question 39

# Multiple Myeloma (MM) the ___ cells are messed up

Answer 39

plasma

Question 40

# MM – Pathophysiology Abnormal clonal ___ cells infiltrating the ___ ◦ Plasma cells and MM cells produced from differentiated B-cells (after antigen stimulation Secrete immunoglobulins ◦ **60% IgG**, 20% IgA, 20% light chain only

Answer 40

plasma bone marrow

Question 41

# MM – Presentation CRAB - ___ >11.5 mg/dL - ___ dysfunction SCr > 2 mg/dL or CrCL < 40 mL/min - ___ < 10 g/dL or 2 g/dL below normal - ___ : one or more osteolytic lesions or pathologic fracture

Answer 41

- calcium - renal - anemia - bone

Question 42

# MM – Treatment Overview - disease is ___ - Goal: disease control

Answer 42

incurable

Question 43

# MM - induction therapy

Answer 43

MM – Agents

Question 44

# Summary of Multiple Myeloma disease is ___ - ___ drugs better than 2 drugs for induction Corner stone of therapy: high dose chemotherapy followed by ___ stem cell rescue ◦ Induction -> consolidation -> maintenance ◦ Better outcomes to transplant with better disease control Several regimens used in the relapse and refractory setting

Answer 44

incurable 3 autologous