Lymphoma Flashcards
What is a major difference between Hodgkin’s Lymphoma and Non-Hodgkin’s Lymphoma?
Hodgkin’s: minority, binomial ages (younger and old!)
Non-Hodgkin’s: majority, occurs as B/T/NK cell
- Graded based on disease progression + aggression
What are all the risk factors for lymphoma?
Male
Old age
Immunosuppression
Infections
Environmental exposures
Radiation
Epstein-Barr
HIV
[my old ignorant in-law expect rich eloquent housewives]
What is the most common type of Non-Hodgkin’s lymphoma?
Diffuse Large B-cell Lymphoma (B-cell lymphoma is most common)
How is Non-Hodgkin’s lymphoma classified?
Classified by step in cell maturation process where mutation occurs
(“Cell of origin”)
What is the clinical presentation of Diffuse Large B-Cell Lymphoma?
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)
What are the specific risk factors for Non-Hodgkin’s lymphoma?
Immunosuppression
Environmental factors
Radiation exposure
What is required for the diagnosis of Non-Hodgkin’s lymphoma?
LYMPH NODE BIOPSY - confirm various mutations including CD20
Imaging- PET, CT scans
Assess cell of origin (Germinal (favorable) or Activated?)
For prognosis assessment of Non-Hodgkin’s lymphoma, what tool is used? What factors are involved with assessment?
International Prognostic Index (IPI)
Age (older = worse)
Lactate dehydrogenase (>3 is bad)
Extranodality
Performance status
Overall risk grouping
What are the TWO preferred treatment regimens of Non-Hodgkin’s?
R-CHOP (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone)
Pola-R-CHP (Polatuzumab vedotin, Rituximab, Cyclophosphamide, Doxorubicin, Prednisone)
H = Doxarubicin, O = Vincristine, don’t question it
What is an alternative to R-CHOP/Pola-R-CHP for Non-Hodgkin’s treatment?
DA-R-EPOCH (Dose Adjusted Rituximab, Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin)
If a Non-Hodgkin’s patient has poor LV ejection fraction, what are preferred first line treatments?
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)
If a Non-Hodgkin’s patient is frail or >80 yo, what is the preferred first line treatment?
R-mini CHOP
(Lower intensity R-CHOP)
If a Non-Hodgkin’s patient has concurrent CNS disease, what are preferred first line treatments?
Lumbar punctures with chemo
High dose methotrexate
What are two considerations of using CHOP in Non-Hodgkin’s?
HIGH emetic risk! (PRN antiemetics)
Moderate febrile neutropenia risk (consider G-CSF after chemo)
What are some AEs with CHOP therapy in Non-Hodgkin’s?
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)
After CHOP, how long should prednisone be continued (including day of chemo)?
5 days prednisone
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?
6 cycles of 21 days
Vincristine = 2 mg maximum
For CD20-positive Non-Hodgkin’s patients, what drug is used? When do we give it timing-wise?
Rituxumab (basically everyone gets)
Administered before CHOP
What are some AEs from using Rituxumab (Non-Hodgkin’s drugs)
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
What did the MInT study find? (Non-Hodgkin’s)
R-CHOP vs CHOP
Rituxumab had significant improvement wo increased toxicity
How is DA-R-EPOCH administered? What is the one difference between typical R-CHOP and this?
Administered as infusion for 4 days then on Day 5 only cyclophosphamide bolus
One difference = Etoposide included
DA-R-EPOCH has ________ lab checks for pt’s ____ and _______. If these are too LOW, then what do we do? If too HIGH?
2x/week lab checks for PLTs andd ANC!
INCREASED PLT/ANC = increase dose
DECREASED PLT/ANC = decrease dose
When should DA-R-EPOCH treatment be considered? (Non-Hodgkin’s) What must ALWAYS be given with this treatment?
Double/Triple hit high grade B cell lymphoma
Poor LVEF
ALWAYS give G-CSF following completion of each chemo cycle
What is given in the alternative R-CHOP therapy instead of vincristine? Why?
Is this alternative superior to R-CHOP?
Polatuzumab vedotin given instead of vincristine
Eliminates synergy with vedotin and worsening peripheral neuropathy
Non-superior to R-CHOP, but also not worse
What are some AEs of Polatuzumab (Non-Hodgkin’s)?
Peripheral neuropathy, constipation, skeletomuscular pain, infusion reactions, anemia, thrombocytopenia, neutropenia
30-40% of Non-Hodgkin’s patients relapse; what are possible REFRACTORY treatments?
Salvage therapy chemo (R-ICE, GDP)
Autologous Stem Cell Transplant
Chimeric Antigen Receptor Therapy (CAR-T)
Bispecific mAb
What is Chronic Lymphocytic Leukemia (CLL)
Accumulation of immunologically dysfunctional B cells
MOST common type of leukemia
What is the clinical presentation of chronic lymphocytic leukemia?
Mostly asymptomatic
(If symptomatic:
Enlarged lymph nodes
Enlarged spleen/liver
B-symptoms [fever, night sweats, weight loss]
Autoimmune cytopenia
Hypogammaglobulinemia)
What two mutations are indicative of WORSE prognosis in chronic lymphocytic leukemia?
del(17p)
TP53
While most people are asymptomatic, what are indications for treatment in CLL?
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
Who should get FIXED treatment vs INDEFINITE treatment for CLL?
FIXED: Younger, fit patients
INDEFINITE: Elderly, less fit patients
What is the FIXED treatment for normal TP53 mutations and TP53/del(17p) mixed mutations?
Obinutuzumab + venetoclax
What is the INDEFINITE treatment for normal TP53 mutations and TP53/del(17p) mixed mutations?
Acalabrutinib +/- [obinutuzumab OR zanubrutinib]
What drug is CCL drug Obinutuzumab similar to? What are some AEs?
Similar to RITUXUMAB (like in R-CHOP)
AEs: infusion reactions, Hepatitis B reactivation, increase viral infection risk
What are Bruton Tyrosine Kinase Inhibitors (BTKi)? (CLL) Name the three that we use.
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
What are some major AEs for the BTKis in CLL. What is one clinical pearl?
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
With Hodgkin’s lymphoma, there is a spike in ___ and _____ patients. They are characterized by _________ cells, which are B cells with 2 nuclei!
Spike in younger and older pts
Characterized by Reed-Sternberg cells
What is the clinical presentation of Hodgkin’s lymphoma?
B-symptoms (FEVER, NIGHT SWEATS, WEIGHT LOSS)
Lymphadenopathy (CD30 (+), usually in neck/underarm)
Generalized malaise (cough, SoB, less appetite)
What lymphoma risk factors are specific to Hodgkin’s lymphoma?
Younger/Older age
Epstein-Barr Virus
HIV infection
What factors could indicate a worse prognosis for Hodgkin’s lymphoma?
≥45 yo
Male
Stage 4 bone marrow biopsy
Albumin < 4
Hgb < 10.5
WBC > 15,000
Lymphocytopenia
What is the GOLD STANDARD treatment for Hodgkin’s lymphoma?
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!)
What are some risks with using ABVD therapy in Hogkin’s? What are some AEs?
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)
What is the method to decrease Bleomycin usage in ABVD regimens (Hodgkin’s)?
Conduct a PET scan after 2 cycles ABVD
If PET score 1-3, may deescalate to AVD for remaining 4 cycles
What is Brentuximab vedotin? When is it used? What must be given with it?
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
What are some refractory Hodgkin’s treatments?
Salvage therapy - ICE, GVD
Autologous Stem Cell transplant
Immunotherapy (Pembrolizumab/nivolumab)
Before starting a Rituxumab-inclusion therapy, what kind of Hepatitis-B panel are we looking for? What would be the prophylaxis for HBV reactivation?
HBsAg (+)
Anti-HBc (+)
IgM Anti-HBc (-)
Anti-HBs (-)
indicates chronic HBV infection
Give entecavir 0.5mg po for prophylaxis
