Lymphoma and MM Flashcards
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
- Reed-Sternberg
- B
HL – Epidemiology
if untreated 90% fatal within 2 to 3 years
Median age at diagnosis: ___
bimodal
39
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
Reed-Sternberg
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
sweats
10
HL - Diagnosis
___ is the gold standard
Excisional biopsy
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
Unfavorable Factors:
* Large mediastinal
adenopathy
* Multiple involve nodal
regions
* B symptoms
* Extranodal involvement
* Significantly elevated
erythrocyte sedimentation
rate (ESR)
HL - Treatment
Goal: ___ while minimizing toxicities and long-term
complications
Modalities
◦ Combination chemotherapy
◦ ABVD
◦ Stanford V
◦ BEACOPP
◦ AAVD
◦ Radiation
◦ Autologous stem cell transplant
CURE
Treatment by Stage
IA, IIA Favorable
- ABVD + RT
- Stanford V + RT
- ABVD
- ABVD + escalated
- BEACOPP
Treatment by Stage
Stage I-II
Unfavorable
- ABVD + RT
- Stanford V + RT
- Escalated BEACOPP x 2 + ABVD x 2 + RT
Treatment by Stage
Stage III/IV
- ABVD ± RT
- AAVD
- Stanford V + RT
- Escalated BEACOPP ± RT (IPS > 3)
ABVD
- doxorubicin
- bleomycin
- vinblastine
- dacarbazine
cardio and pulm toxicity
ABVD
high amount of neutropenia
low amount of infecction
we dont know why
AAVD
- doxorubicin
- brentuximab vendotin
- vinblastine
- dacarbazine
Relapsed HL
- High dose chemotherapy with ____ stem cell rescue
- Maintenance therapy if high risk of relapse with brentuximab vedotin following stem cell transplant
autologous
HL summary
Early stage disease
◦ Involved-field radiation
◦ 2-4 cycles of ___ chemotherapy
ABVD
HL summary
Advanced stage disease
◦ 6-8 cycles of ___ or ___ chemotherapy
◦ ___ preferred in younger patients with Stage III or IV
- ABVD, AAVD
- AAVD
HL summary
Relapsed disease
◦ High-dose chemotherapy followed by ___ cell rescue
Maintenance therapy (high risk disease post transplant)
◦ ___
- stem
- Brentuximab vedotin
Non Hodgkin Lymphoma (NHL)- epidemiology
Median age at diagnosis: ___
5-year survival rate: 74.3%
68
NHL – Pathophysiology
Malignant __ or ___ lymphocytes and ___
Malignant cells proliferate and replace normal cells in the lymph nodes and/or bone marrow
B
T
precursors
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
- Fever (greater than 38oC)
- Drenching sweats, especially at night
- Unintentional weight loss
of greater than 10 % in < 6 months - excisional
NHL: B-Cell Lymphomas
Indolent (25-40%)
- Relatively ___ survival
- Usually ___
- Follicular (Grade 1 or 2)
* Marginal zone
* Small lymphocytic lymphoma
- long
- incurable
NHL: B-Cell Lymphomas
Aggressive (60-75%)
- Rapid growth
- ___ survival if untreated
- Usually ___
- Follicular (Grade 3)
- ___ (DLBCL)
short
curable
Diffuse large B-cell
NHL: B-Cell Lymphomas
Highly Aggressive
- Doubling time = 18 hours
- Usually ___
- Burkitt’s
- Lymphoblastic
- AIDS-related
curable
NHL – Treatment Approaches
Treatment depends on subtype, staging, and patient factors
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
Richter’s Transformation
- Follicular lymphoma can transform into an aggressive NHL!!
- Chemotherapy yields 40% CR (of the DLBCL) but: Still have underlying follicular lymphoma
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
70
NHL Multi-Agent Chemotherapy
R-CHOP
- rituximab
- cyclophosphamide
- doxorubicin
- vincristine
- prednisone
NHL Multi-Agent Chemotherapy
DA-EPOCH +
rituximab
- Etoposide 50
- Prednisone 60
- Vincristine 0.4
- Doxorubicin 10
- Cyclophosphamide
- rituximab
*Dose-adjustment paradigm based on twice weekly CBC (nadir ANC count
NHL Multi-Agent Chemotherapy
Pola + R+ CHP
Polatuzumab vedotin
Rituximab
Cyclophosphamide
Doxorubicin
Prednisone
DLBCL Treatment
- ___ and ___ mostly
R-CHOP
Pola - R -CHP
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
- reactivation
- surface
- core
- entecavir
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
gram colony stimulating factors
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
Curative
- salvage, autologous
CAR T-cell in NHL
3 drugs
all target ___
CD19
- Tisagenlecleucel
- Axicabtagene ciloleucel
- Lisocabtagene
maraleucel
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
makes T cell and cancer hold hands
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
- on
- impairs
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 ___
corticosteroids
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%
- ABVD
- R-CHOP
Multiple Myeloma (MM)
the ___ cells are messed up
plasma
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
plasma
bone marrow
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
- calcium
- renal
- anemia
- bone
MM – Treatment Overview
- disease is ___
- Goal: disease control
incurable
MM - induction therapy
MM – Agents
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
incurable
3
autologous
