Heme/onc midterm

what is lymphoma

cancer of the lymphatic system

age distribution of hodgkin lymphoma

-15-30 years

->55 years old

hodgkins lymphoma is one of the most _____ hematologic maliganacies

curable

CHL

Classical Hodgkin Lymphoma

NLPHL

Nodular lymphocyte predominant Hodgkin's lymphoma

CHL key feature

-reed-sternberg cell in an inflammatory background

-large, binucleated cell

-owl eyes

-expressed CD30 and CD15

NLPHL key feature

-lymphocyte predominant cells

-popcorn cells

most common type of hodgkins lymphoma

classical

etiology of hodgkins lymphoma

-unknown

-connected to infectious exposure

-epstein barr virus

-immunocompromised patients are at higher risk

clinical presentation of hodgkins lymphoma

-painless enlarged lymph nodes, persistent > 2 months

-mediastinal mass

-B symptoms

what are B symptoms

-fever >100.4 degrees F

-drenching night sweats

-weight loss >10% within 6 months

diagnosis of hodgkins lymphoma

-lymph node biopsy

-assess symptoms and performance status

-CBC, CMP, LDH, ESR

-PET-CT scans

ann arbor staging system

I-IV

stage I ann arbor stage

involvement of a single lymph node region or structure or of a single extralymphatic organ or site

stage II ann arbor stage

involvement of two or more lymph node regions on the same side of the diaphragm or localized involvement of an extralymphatic organ or site and of one or more lymph node regions on the same side of the diaphragm

stage III ann arbor stage

involvement of lymph node regions on both sides of the diaphragm, which may also be accompanied by localized involvement of an extralymphatic organ or site or by involvement of the spleen or both

stage IV ann arbor stage

diffuse or disseminated involvement of one or more extralymphatic organs or tissues with or without associated lymph node enlargement

early stage favorable hodgkins lymphoma

stage I-II with no unfavorable factors

early stage unfavorable hodgkins lymphoma

stage I-II with unfavorable factors

advanced stage hodgkins lymphoma

stage III-IV, advanced stage disease is considered unfavorable

what is used for prognosis in advanced disease (III-IV)

international prognostic score (IPS)

international prognostic score (IPS)

-1 point per factor

-albumin <4 g/dL

-hemoglobin <0.5 g/dL

-male

-age >/= 45

-stage IV disease

-leukocytosis

-lymphocytopenia

treatment principles for hodgkins lymphoma

-goal to cure

-minimize short and long term treatment complications

treatment modalities of hodgkins lymphoma

-chemo

-radiation

-surgery = minimal role

interim FDG-PET imaging

-important role in prognosis and treatment decisions

-informs treatment adaptation

-response determined utilizing deauville criteria

what is the Deauville criteria

measuring hodgkins lymphoma response to treatment through PET scans

stage IA-IIA favorable treatment

-ABVD x 2 cycles

-restage with FDG-PET/CT

-ABVD 1-2 cycles +/- ISRT or AVD x 4 cycles

ISRT

involved site radiation therapy

first line options for stage I-II unfavorable hodgkins lymphoma

-ABVD x 2 cyles

-nivolumab + AVD x 4 cycles + ISRT

-brentuzumab vedotin + AVD x 4 cycles +ISRT

-BrECADD x 2 cycles

what do we need to do after giving first part of hodgkins lymphoma treatment

restage with FDG-PET/CT

after giving BrECADD x 2 cycles for stage I-II unfavorable hodgkins lymphoma, what are we giving next

-BrECADD x 2 cycles (deauville 1-3)

-BrECADD x 4 cycles (deauville 4-5)

THEN

repeat staging for treatment plan

after giving nivolumab + AVD + ISRT OR brentuximab vedotin + AVD +ISRT for stage I-II unfavorable hodgkins lymphoma, what are we doing next

-surveillance (deauville 1-3)

OR

-biopsy (deauville 4-5)

THEN

-surveillance (biopsy negative )

-treat as primary refractory disease (biopsy positive)

after giving ABVD x 2 cycles for stage I-II hodgkins lymphoma, what are we doing next

-ABVD x 2 cycles or AVD x 4 cycles (deauville 1-3)

OR

-ABVD x 2 cycles or BrECADD x 2 cycles (deauville 4-5)

THEN

-repeat staging for subsequent treatment plan

preferred treatment of stage III-IV treatment for hodgkins lymphoma

-BrECADD x 2 cycles

-nivolumab + AVD x 6 cycles

after giving BrECADD x 2 cycles for stage III-IV hodgkins lymphoma, what are we going next

-restage

-BrECADD x 2 cycles (deauville 1-3)

OR

-biopsy (deauville 4-5)

THEN

-BrECADD x 4 cycles (biopsy negative)

-treat as refractory disease (biopsy positive)

ABVD regimen

-Doxorubicin

-Bleomycin

-Vinblastine

-Dacarbazine

cycle duration of ABVD regimen

all given day 1 and day 15 of a 28 day cycle

AVD regimen

-doxorubicin

-vinblastine

-dacarbazine

BV+AVD regimen

-brentuximab vedotin

-doxorubicin

-vinblastine

-dacarbazine

what chemo drugs do we need growth factors for

brentuximab vedotin

nivolumab + AVD regimen

-nivolumab

-doxorubicin

-vinblastine

-dacarbazine

BrECADD regimen

-brentuximab vedotin

-etoposide

-cyclophosphamide

-doxorubicin

-dacarbzine

-dexamethasone

second line therapy for relapsed/refractory disease

-combination chemo, use of immune checkpoint inhibitors and brentuximab vedotin

-high dose therapy and autologous stem cell rescue

-brentuximab vedotin maintenance if high risk

reed-sternberg cells highly express what

PD-L1

PD-L1 inhibitor

nivolumab

MOA of doxorubicin

Anthracycline, topoisomerase II inhibition, DNA intercalation via receptors with phosphatases, generates free radicals with interaction with iron and copper

why do we give doxorubicin via a central line

it is a vesicant

toxicity of doxorubicin

-Cardiotoxicity

-myelosuppression

-N/V

-hair loss

-red bodily fluids

doxorubicin has a lifetime dose limit of 550 mg/m2, what can we give to patients that have received >300 mg/m2

dexrazoxane

MOA of bleomycin

antitumor antibiotic that inhibits DNA by binding to DNA and causing single and double strand breaks

toxicity of bleomycin

-pulmonary toxicity

-hypersensitivity

-renal and hepatic toxicity

most common presentation of bleomycin toxicity

pneumonitis progressing to pulmonary fibrosis

risk factors for bleomycin pulmonary toxicity

-older age

-cumulative bleomycin dose

-pulmonary irradiation

-prior history of lung disease

-smoking history

-use of G-CSF

MOA of vinblastine

vinca alkaloid, inhibits microtubule formation leading to cell cycle arrest

what drug is a vesicant that must be given in an IV minibag

vinblastine

toxicity of vinblastine

-peripheral neuropathy

-myelosuppression

-constipation

MOA of dacarbazine

alkylating agent, intercalates in DNA, leading to double strand breaks and cell death

toxicities of dacarbazine

-myelosuppression

-N/V (high)

-reproductive toxicity risk

what regimen has no routine use of growth factors

ABVD

MOA of brentuximab vedotin

antibody drug conjugate, mAb antibody against CD30 connected to MMAE, a microtubule disrupting agent

toxicities of brentuximab vedotin

-peripheral neuropathy

-myelosuppression

-constipation

-rash

MOA of nivolumab

immune checkpoint inhibitor, binds to PD-1 on T cells and blocks interaction between PD-L1 on tumor cells

toxcities of nivolumab

-immune related adverse effects

-colitis

-dermatitis/rash

-hepatitis

-endocrinopathies

-pneumonitis

long term complications of hodgkins lymphoma treatment

-secondary malignancies

-infertility

-cardiopulmonary diseases

-hypothyroidism

types of non-hodgkins lymphoma

T cell and B cell

types of B cell lymphomas

-follicular lymphoma

-diffuse large B cell lymphoma (DLBCL)

-burkitt lymphoma

what cell type is least common in non hodgkin lymphoma

NK cell

median age of diagnosis for non-hodgkins lymphoma

67

what is expressed on B cell lymphoma

CD20

double hit or triple hit B cell lymphoma

more aggressive subtype of disease, requires more intense treatment

etiology of non-hodgkins lymphoma

-chemical exposure

-prior chemo/radiation exposure

-immunocomprised

-history of certain infections

clinical presentation of non-hogkins lymphoma

-enlarged lymph nodes

-enlarged liver or spleen

-abdominal pain, bowel obstruction

-anemia, neutropenia, thrombocytopenia

-B symptoms

what lymphoma often involves lymph nodes, spleen, bone marrow

B cell lymphoma

what lymphoma often involves skin and lungs

T cell lymphoma

diagnosis of non-hodgkins lymphoma

-biopsy of lymph node

-history and physical

-lab tests

-CT scans and chest X ray

-bone marrow biopsy

aggressive non-hodgkins lymphoma

-fast growing

-requires treatment

-cure possible

types of aggressive non-hodgkins lymphoma

-diffuse large B cell lymphoma

-Burkitt lymphoma (very aggressive)

Indolent non-Hodgkin lymphoma

-slow growing

-can have long survival even without treatment

-incurable

types of indolent non-hodgkins lymphoma

-follicular lymphoma

-mantle cell lymphoma

-marginal zone lymphoma

stage I limited non-hodgkins lymphoma

one node or a group adjacent nodes

stage II limited non-hodgkins lymphoma

two or more nodal groups on the same side of the diaphragm

stage III advanced non-hodgkins lymphoma

nodes on both sides of the diaphragm or nodes above the diaphragm with spleen involvement

stage IV advanced non-hodgkins lymphoma

additional non-contiguous extra-lymphatic involvement

FLIPI score

follicular lymphoma international prognostic index score

follicular treatment principles

-goal = control

-indolent disease does not always require immediate treatment

stage I-II treatment of follicular lymphoma

-radiation alone

OR

-anti-CD20 monoclonal antibody

-(+/-) chemo

-(+/-) radiation

stage III-IV treatment of follicular lymphoma

anti-CD20 mAb +/- chemo

second line treatment of follicular lymphoma

-bendamustine + obinutuzumab or rituximab

-CHOP + obinutuzumab or rituximab

-CVP + obinutuzumab or rituximab

-lenalidomide +/- rituximab

-lenalitomide + rituximab + epcoritamab or tafasitamab

third line regimen for follicular lymphoma

-bispecfic antibody therapy

-CD19 CAR-T cell therapy

MOA of rituxumab

mAb targeting CD20 on B cells

what drug do we need an initial slow titration to minimize infusion reactions

rituximab

rituximab toxicity

-infusion reactions

-tumor lysis syndrome

-severe mucocutaneous reactions

-progressive multifocal leukoencephalopathy

obinutuzumab MOA

mAb targeting CD20 on B cells

obinutuzumab toxicity

-hepatitis D reactivation

-progressive multifocal leukoencephalopathy

-infusion reactions

-neutropenia

-tumor lysis syndrome

-infection risk

MOA of bendamustine

alkylating agent, forms interstrand DNA crosslinks, leading to cell death

bendamustine toxicity

-myelosuppression

-N/V/D

-rash

-fatigue

-infection risk

DLBCL

Diffuse large B-cell lymphoma

treatment principles of DLBCL

-goal to cure

-requires treatment

-treated with chemo

-high risk of tumor lysis syndrome with initial treatment

what scoring index is used in DLBCL

international prognostic index score (IPI)

prognosis of germinal center B cell subtype of DLBCL

better prognosis