Mutations and CDs
Which translocation(s) are associated with Burkitt lymphoma
t(8;14) – most common
t(2;8)
t(8;22)
How do you differentiate between germinal vs non-germinal cell DLBCL?
Hans algorithm
--> Based on 3 markers--> CD10,BCl-6, MUM1
--> Remember that the CD10 and BCL6 are germinal center markers
--> Therefore CD10+ is GCB
--> BCl6 + (CD10 -ve and MUM-ve) is GCB
--> GCB is better!!!! 76% five year OS in GCB vs 34% in Non GC
Polarix Trial
--> In patients with previously untreated intermediate-risk or high-risk DLBCL [IPI score 2-5], the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP.
--> PFS in Pola-R-CHP > RCHOP.
--> Subgroup analysis--> PFS in Pola-R-CHP > RCHOP only in ABC.
--> No difference in the PFS in GCB.
--> These subsets can be defined on Gene expression profiling.
--> It can also be done via IHC using Han's algorithm, but 20% of patients can be misclassified therefore, we should utilize GEP.
Polatuzumab Vedotin mechanism of action, adverse effects
Anti-CD79 b Antibody drug conjugate.
The most common adverse reactions (≥20%) included myelosuppression (neutropenia, thrombocytopenia, anemia), peripheral neuropathy, fatigue, diarrhea, pyrexia, decreased appetite, and pneumonia.
--> OTHER WARNINGS AND PRECAUTIONS
- Infections.
-Infusion-Related Reactions
- Progressive Multifocal Leukoencephalopathy (PML): Monitor patients for new or worsening neurological, cognitive, or behavioral changes suggestive of PML
- Tumor Lysis Syndrome:
- Hepatotoxicity
FDA Approved CAR-T drugs approved in DLBCL?
Anti-CD19 CAR T-cell Constructs
--> Axicabtagene ciloleucel [Lets just call it Axi-cel]
--> Tisagenlecleucel [Tisa]
-->Lisocabtagene maraleucel [Liso]
* CAR-T therapies were initially approved for 3 rd and later line therapies. *****Even the patient's who have failed ASCT can be cured by CART!!!!!
* Now, it has also been approved in patients who relapsed within 12 months of Ritux-based therapy or were refractory. It is better than ASCT in such cases.
What is a double or triple hit DLBCL?
Double hit--myc, BCl 2/or 6 rearrangenment--Bad!!!
drug resistant, very proliferative, poor prognosis.
Triple hit-- myc, BCL2 and 6 rearrangement--Bad!!!!!
*****Remember that the standard R-CHOP is suboptimal!
Management of Relapsed/Refractory DLBCL-- 1st line options
--> Evaluate if they are a candidate for an Autologous stem cell transplant?
--> Ineligible patients should go to 2nd and 3 rd line options.
--> Patients eligible for ASCT should receive platinum-based salvage therapy[RdHAP, RICE]. Only 50% patients will respond to it and will get ASCT. The ones who did not respond (platinum refractory) should go to 3 rd line options.
--> CART has also been approved in patients who relapsed within 12 months of Ritux-based therapy or were refractory. It is better than ASCT in such cases.
CAR-T Toxicities?
-> Cytokine release syndrome (CRS)--IL-6 mediated--IL-6 receptor antagonist, Tocilizumab --1st line.
--> Immune effector cell-associated neurotoxicity syndrome (ICANS)--> managed with steroids.
--> Prolonged cytopenias
--> B cell aplasia
--> Hypogammaglobinemia
Staging workup for DLBCL?
--> PET [if it doesn't show bone marrow disease, do a bone marrow biopsy to rule out stage IV disease]
--> TLS labs
--> Hep B testing
--> Echo
--> IPI score[ APLES--Age> 60, performance status>=2, LDH level >1× normal, Extranodal site(>1 site), Stage III-IV ]--3 is High-intermediate risk group, 4 and 5 are high risk group, 3-5 have poor prognosis.
Name 2nd and 3rd line regimens
-> CAR-T
-> Polatuzumab vedotin +BR
--> Tafasitamab-Lenalidomide [Tafasitamab is a CD19 monoclonal antibody]
--> Selinexor
--> Loncastuximab Teserine [Anti CD19 ADC]
--> Investigational trials
--> CD3/CD20 Bispecific Antibodies[Glofitamab, epcoritamab]
True/false
CD3/20 bispecific antibodies can be used in DLBCL with prior ASCT or prior CART?
True!
Ann Arbor staging?
How do you treat non-bulky limited disease?
I: single LN group
II: Multiple LNs on one side of the diaphragm
III: Multiple LN's involving both sides of the diaphragm
IV: Involvement of extranodal sites
--> Non-bulky limited disease (i.e confined to one area and < 7.5 cm)-->can manage with 3 cycles of R-CHOP followed by restaging and if Complete or partial response, follow up with RT.
--> If bulky limited ds--RCHOP X6 cycles+RT
--> Extensive stage DLBCL--RCHOP X6 cycles, PET at 2-4 cycles/mini RCHOP for > 80 years old.
Name the drugs in R-EPOCH and who needs it?
Ritux, Etoposide, Prednisone, vincristine, cyclophosphamide and doxorubicin.
Double or triple hit, primary mediastinal, grey zone, HIV lymphomas.
True/false
CHOP-based therapy is NOT adequate for Burkitt Lymphoma.
True!
Dose-intensive regimens needed (e.g. CODOX-M, DA-EPOCH, hyper-CVAD)