CAR- T therapy for highly aggressive B cell lymphoma

Axicel versus tiso cel:

Axi cel with better PFS, and OS than tiso cel when compared in patients who did not go on trial. More grade 3 ICANS with Axicel.

https://www.nature.com/articles/s41591-022-01969-y

Lisocel has a better toxicity profile than Axicel, although premed with steroids helps reduce the incidence of CRS with axicel.

RTP Pan Pacific 2022

https://www.researchtopractice.com/UNMCPanPacific22CART/Video/1?playlistIndex=0#t=3m46s

Double hit lymphoma

•  Less than 10% of lymphoma are DH or TH
• Ideally, all high-grade lymphomas should be tested for double and triple hit, definitely all GCB types
• Chromosome 2 ( kappa light chain), 
• chromosome 3 ( BCL6)
• Chromosome 8 ( c-myc), 
• Chr 14( heavy chain IGH), 
• chr 18 ( BCL-2), 
• chr 22 ( lambda)
• In addition to usual lymphoma testing, viral and cardiac tests, also do LP and CSF cytology in double hit
• If CSF positive or CNS symptoms--> get MRI brain
• Treatment: DA R EPOCH for denovo
• Add 4 cycles IT methotrexate
• If CSF positive, place Omaya , add systemic MTX and cytarabine with CHOP
• If CNS involvement and pt gets to CR--> auto SCT
• Frail, > 80 yr , cardiac dysfunction or cannot use anthracycline-->R-CGOP (rituximab, cyclophosphamide, gemcitabine, vincristine, and prednisone).

Ovarian cancer front line

 Three main considerations:

1. Surgery upfront or NACT followed by interval surgery

2. Choice of front-line chemo

3. Molecularly targeted therapy: HRD, BRCA

Primary surgery depends on patient's clinical condition and the possibility of complete cytoreduction.

If NACT 3 cycles chemo--> surgery--> 3 cycles chemo

Choice of chemo

Standard: carbo taxol 3 week. Total 6 cycles

Molecular therapy:

Bevacizumab: improves PFS

The biggest change has been in BRCA improves OS as maintenance. 

In the maintenance setting:

BRCA mutated: niraparib ( PRIMA), Olaparib with or without avastin

BRCA WT but HRD: Niraparib, olaparib

BRCA WT, HRD p: niraparib, avastin

Immunotherapy for coagulation disorders

 Antibodies in X linked hemophilia

These are alloantibodies acquired after prior plasma-derived or recombinant factor 8. It can start as early as within 20 exposure days. Bypass agents are formally indicated and patients are treated with immune tolerance therapy. Occasionally immunosuppression is used. Spontaneous remission is rare, and mortality is high due to bleeding risk.

Antibodies in acquired hemophilia ( AHA)

These are autoantibodies. 50% of these are idiopathic, but look for cancer, autoimmune conditions, drug-induced and postpartum. Interestingly, postpartum acquired hemophilia can go into remission in 20-30% cases. Bypass agents can be used but not formally indicated as with X linked. In contrast, immune suppression ( IST) is indicated, but ITI is not typically used.

A word about immune tolerance therapy ( ITI)

More successful in Hemophilia A versus Hemophilia B. 70% versus 30%.

Small doses of factor 8 are introduced daily in those with high titers of inhibitor. High dose is preferred to low dose based on a 2012 study which showed faster improvement in high dose cohort and higher bleeding in low dose cohort.

ITI typically in good prognosis patients, IST in poor prognosis patients.

IST treatment in acquired hemophilia

High risk or low risk.

High risk: Inhibitor > 20 BU, factor 8 less than 1%

Low risk : inhibitor < 20 BU, factor 8> 1%

Mortality in acquired hemophilia: 20% in those over 65 yr.

CV complication, risk of infection and risk of bleeding. Also prognosis is determined by the underlying condition responsible for AHA.

Reference Blood Journal Sept 8, 2022

Alloantibodies in VWD are always in type 3. Difficult to treat. Routine testing is not done. Inhibitors may cause anaphylaxis when VWF is infused. Suspect this if a loss of response to VWF Infusions.

Acquired VWD: MGUS, malignancies, aortic stenosis etc.

Treat underlying condition.

Combination of VWF/factor 8 concentrates, IVIG, IST, DDAVP.