Lymphoma

Question 1

What is a major difference between Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma?

Answer 1

Hodgkin’s: minority, binomial ages (younger and old!)
Non-Hodgkin’s: majority, occurs as B/T/NK cell
- Graded based on disease progression + aggression

Question 2

What are all the risk factors for lymphoma?

Answer 2

Male
Old age
Immunosuppression
Infections
Environmental exposures
Radiation
Epstein-Barr
HIV

[my old ignorant in-law expect rich eloquent housewives]

Question 3

What is the most common type of Non-Hodgkin’s lymphoma?

Answer 3

Diffuse Large B-cell Lymphoma (B-cell lymphoma is most common)

Question 4

How is Non-Hodgkin’s lymphoma classified?

Answer 4

Classified by step in cell maturation process where mutation occurs
(“Cell of origin”)

Question 5

What is the clinical presentation of Diffuse Large B-Cell Lymphoma?

Answer 5

B-symptoms (FEVER, NIGHT SWEATS, WEIGHT LOSS)
Nodal masses (nodes full of immature cells)
Increased Lactate Dehydrogenase (cell turnover marker, since lymph nodes swell and cause cell lysis)
Bone marrow involvement
Altered mental status
Increased SCr, uric acid, liver enzymes, electrolytes (tumor lysis syndrome)

Question 6

What are the specific risk factors for Non-Hodgkin’s lymphoma?

Answer 6

Immunosuppression
Environmental factors
Radiation exposure

Question 7

What is required for the diagnosis of Non-Hodgkin’s lymphoma?

Answer 7

LYMPH NODE BIOPSY - confirm various mutations including CD20
Imaging- PET, CT scans
Assess cell of origin (Germinal (favorable) or Activated?)

Question 8

For prognosis assessment of Non-Hodgkin’s lymphoma, what tool is used? What factors are involved with assessment?

Answer 8

International Prognostic Index (IPI)
Age (older = worse)
Lactate dehydrogenase (>3 is bad)
Extranodality
Performance status
Overall risk grouping

Question 9

What are the TWO preferred treatment regimens of Non-Hodgkin’s?

Answer 9

R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)
Pola-R-CHP (Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone)

H = Doxarubicin, O = Vincristine, don’t question it

Question 10

What is an alternative to R-CHOP/Pola-R-CHP for Non-Hodgkin’s treatment?

Answer 10

DA-R-EPOCH (Dose Adjusted Rituximab, Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin)

Question 11

If a Non-Hodgkin’s patient has poor LV ejection fraction, what are preferred first line treatments?

Answer 11

DA-R-EPOCH (contains cardiotoxic drug Doxorubicin but slower infusion is ok!)

Alts:
- R-CDOP (rituximab, cyclophosphamide, liposomal doxorubicin, prednisone)
- R-GCVP (rituximab, gemcitabine, cyclophosphamide, vincristine, prednisone)
- R-CEOP (rituximab, cyclophosphamide, etoposide, vincristine, prednisone)

Question 12

If a Non-Hodgkin’s patient is frail or >80 yo, what is the preferred first line treatment?

Answer 12

R-mini CHOP
(Lower intensity R-CHOP)

Question 13

If a Non-Hodgkin’s patient has concurrent CNS disease, what are preferred first line treatments?

Answer 13

Lumbar punctures with chemo
High dose methotrexate

Question 14

What are two considerations of using CHOP in Non-Hodgkin’s?

Answer 14

HIGH emetic risk! (PRN antiemetics)
Moderate febrile neutropenia risk (consider G-CSF after chemo)

Question 15

What are some AEs with CHOP therapy in Non-Hodgkin’s?

Answer 15

Infections, fatigue anemia, thrombocytopenia, alopecia
Doxorubicin: cardiotoxicity (anthracycline, limit max lifetime dose <500)
Vincristine: peripheral neuropathy
Cyclophosphamide: hemorrhagic cystitis
Prednisone: insomnia, GI upset, high BG (steroid effects)

Question 16

After CHOP, how long should prednisone be continued (including day of chemo)?

Answer 16

5 days prednisone

Question 17

How many cycles of CHOP are usually used in Non-Hodgkin’s? What is the maximum vincristine that can be given in any one cycle?

Answer 17

6 cycles of 21 days
Vincristine = 2 mg maximum

Question 18

For CD20-positive Non-Hodgkin’s patients, what drug is used? When do we give it timing-wise?

Answer 18

Rituxumab (basically everyone gets)
Administered before CHOP

Question 19

What are some AEs from using Rituxumab (Non-Hodgkin’s drugs)

Answer 19

Infusion rxn (PREMEDICATE w APAP and Benadryl, first cycle titration = 6 hrs!)
Hepatitis B reactivation (check hepatitis panel before use)
Hypogammaglobulinemia/infections
GI perforations (consider holding Rituxumab)
Rare - PML

Question 20

What did the MInT study find? (Non-Hodgkin’s)

Answer 20

R-CHOP vs CHOP
Rituxumab had significant improvement wo increased toxicity

Question 21

How is DA-R-EPOCH administered? What is the one difference between typical R-CHOP and this?

Answer 21

Administered as infusion for 4 days then on Day 5 only cyclophosphamide bolus

One difference = Etoposide included

Question 22

DA-R-EPOCH has ________ lab checks for pt’s ____ and _______. If these are too LOW, then what do we do? If too HIGH?

Answer 22

2x/week lab checks for PLTs andd ANC!

INCREASED PLT/ANC = increase dose
DECREASED PLT/ANC = decrease dose

Question 23

When should DA-R-EPOCH treatment be considered? (Non-Hodgkin’s) What must ALWAYS be given with this treatment?

Answer 23

Double/Triple hit high grade B cell lymphoma
Poor LVEF
ALWAYS give G-CSF following completion of each chemo cycle

Question 24

What is given in the alternative R-CHOP therapy instead of vincristine? Why?
Is this alternative superior to R-CHOP?

Answer 24

Polatuzumab vedotin given instead of vincristine
Eliminates synergy with vedotin and worsening peripheral neuropathy
Non-superior to R-CHOP, but also not worse

Question 25

What are some AEs of Polatuzumab (Non-Hodgkin’s)?

Answer 25

*Peripheral neuropathy*, constipation, skeletomuscular pain, infusion reactions, anemia, thrombocytopenia, neutropenia

Question 26

30-40% of Non-Hodgkin’s patients relapse; what are possible REFRACTORY treatments?

Answer 26

Salvage therapy chemo (R-ICE, GDP) Autologous Stem Cell Transplant Chimeric Antigen Receptor Therapy (CAR-T) Bispecific mAb

Question 27

What is Chronic Lymphocytic Leukemia (CLL)

Answer 27

Accumulation of immunologically dysfunctional B cells *MOST common type of leukemia*

Question 28

What is the clinical presentation of chronic lymphocytic leukemia?

Answer 28

Mostly asymptomatic (If symptomatic: Enlarged lymph nodes Enlarged spleen/liver B-symptoms [fever, night sweats, weight loss] Autoimmune cytopenia Hypogammaglobulinemia)

Question 29

What two mutations are indicative of WORSE prognosis in chronic lymphocytic leukemia?

Answer 29

**del(17p) TP53**

Question 30

While most people are asymptomatic, what are indications for treatment in CLL?

Answer 30

Disease-related sx (severe fatigue, weight loss, night sweats) End organ dysfunction Bulky disease (splenomegaly/lymphadenopathy) Bone marrow failure Anemia, thrombocytopenia (unresponsive to corticosteroids) Increase in absolute lymphocyte count (ALC) ≥50% over 2 months Extranodal involvement

Question 31

Who should get FIXED treatment vs INDEFINITE treatment for CLL?

Answer 31

FIXED: Younger, fit patients INDEFINITE: Elderly, less fit patients

Question 32

What is the FIXED treatment for normal TP53 mutations and TP53/del(17p) mixed mutations?

Answer 32

**Obinutuzumab + venetoclax**

Question 33

What is the INDEFINITE treatment for normal TP53 mutations and TP53/del(17p) mixed mutations?

Answer 33

**Acalabrutinib +/- [obinutuzumab OR zanubrutinib]**

Question 34

What drug is CCL drug Obinutuzumab similar to? What are some AEs?

Answer 34

Similar to RITUXUMAB (like in R-CHOP) AEs: infusion reactions, Hepatitis B reactivation, increase viral infection risk

Question 35

What are Bruton Tyrosine Kinase Inhibitors (BTKi)? (CLL) Name the three that we use.

Answer 35

Block B-cell receptor signaling cascade by binding to BTK enzyme and stops further creation of B cells Second gen BTKis are more selective for cysteine 481 (less “off-target” effects) *1st gen* = Ibrutinib *2nd gen* = **Acalabrutinib, Zanubrutinib**

Question 36

What are some major AEs for the BTKis in CLL. What is one clinical pearl?

Answer 36

Ibrutinib = Neutropenia, HTN, **arrhythmia** Acalabrutinib = HAs, muscle pain (“push through”, will self-resolve; consider APAP for relief) Zanubrutinib = Myelosuppression, contusions (much less arrhythmia)= Pearl: transient increase in absolute lymphocyte count at start, does not mean worsening disease

Question 37

With Hodgkin’s lymphoma, there is a spike in ___ and _____ patients. They are characterized by _________ cells, which are B cells with 2 nuclei!

Answer 37

Spike in **younger** and **older** pts Characterized by **Reed-Sternberg cells**

Question 38

What is the clinical presentation of Hodgkin’s lymphoma?

Answer 38

B-symptoms (FEVER, NIGHT SWEATS, WEIGHT LOSS) Lymphadenopathy (**CD30 (+)**, usually in neck/underarm) Generalized malaise (cough, SoB, less appetite)

Question 39

What lymphoma risk factors are specific to Hodgkin’s lymphoma?

Answer 39

Younger/Older age Epstein-Barr Virus HIV infection

Question 40

What factors could indicate a worse prognosis for Hodgkin’s lymphoma?

Answer 40

≥45 yo Male Stage 4 bone marrow biopsy Albumin < 4 Hgb < 10.5 WBC > 15,000 Lymphocytopenia

Question 41

What is the GOLD STANDARD treatment for Hodgkin’s lymphoma?

Answer 41

ABVD (Doxorubicin (A, dont question), Bleomycin, Vinblastine (similar to vincristine) Dacarbazine Given every 14 days Advanced stage can add targeted therapies like Brentuximab vedotin (like Polatuzumab!)

Question 42

What are some risks with using ABVD therapy in Hogkin’s? What are some AEs?

Answer 42

Considerations: High emetic risk, febrile neutropenia AEs: Doxorubicin - **cardiotoxicity** Bleomycin - **pulmonary toxicity** especially with growth factor Vinblastine - peripheral neuropathy (like vincristine) Dacarbazine - cytopenias (Try to minimize Bleomycin use if possible! Quite toxic)

Question 43

What is the method to decrease Bleomycin usage in ABVD regimens (Hodgkin’s)?

Answer 43

Conduct a PET scan after 2 cycles ABVD If PET score 1-3, may deescalate to AVD for remaining 4 cycles

Question 44

What is Brentuximab vedotin? When is it used? What must be given with it?

Answer 44

Anti-CD30 Ab conjugate Used in ADVANCED HODGKIN’S LYMPHOMA Given with rituximab, cyclophosphamide, doxorubicin, prednisone MUST be given with GROWTH FACTOR plus AVD standard therapy

Question 45

What are some refractory Hodgkin’s treatments?

Answer 45

Salvage therapy - ICE, GVD Autologous Stem Cell transplant Immunotherapy (Pembrolizumab/nivolumab)

Question 46

Before starting a Rituxumab-inclusion therapy, what kind of Hepatitis-B panel are we looking for? What would be the prophylaxis for HBV reactivation?

Answer 46

HBsAg (+) Anti-HBc (+) IgM Anti-HBc (-) Anti-HBs (-) *indicates **chronic HBV infection*** Give **entecavir 0.5mg po** for prophylaxis