How would you treat an elderly newly diagnosed tDLBCL that has previously seen R-CHOP and Bendamustine-Obinutuzumab prior to the transformative event?

I would give tafasatimab and Revlimid per the L-MIND study. I have been so impressed by this well tolerated immunotherapy regimen and the durability of responses. Literally, it looks competitive with car T cell therapy. Car, T cells would be an option, if the patient is very fit for their age and the disease is not extremely extensive to cause unacceptable CIRS or ICANS.

If the goal is palliation then Tafasitamab + lenalidomide or bi-specifics. If the goal is cure and the patient is reasonably fit, then CAR T.

It's a tough question, as there's no single standard of care approach here, especially because the patient-specific details really matter here. Options basically boil down to whether the patient is felt to benefit more from a cytotoxic approach or from a T-cell engaging approach. Approaches could be to administer a 1L DLBCL regimen (e.g. R-da-EPOCH, which can be given safely with prior RCHOP exposure given normal cardiac function at this point) with the intention of consolidating autotransplant ...

Interesting case. In a similar case, I gave R-GCVP and achieved long remission. However, it depends on the time interval between prior regimens. If it was short, I’d probably do something like Len-Rituximab or Len-Tafa and justify the patient is transplant-ineligible.

I would test his candidacy for CD19 CAR-T with Liso-Cel and if eligible, I would offer it to him. The PILOT study (Sehgal et al., PMID 35839786) showed that the transplant-ineligible population (including those age 70 and above) achieved an ORR of 80% (54% CR) and those achieving CR have a long duration of remission. Outside of this option, I would look for a clinical trial. My 3rd option will be Tafa-Len. I would not offer autoSCT for an elderly patient with transformed lymphoma after 2 lines o...

Taftasimab and lenalidomide: well tolerated in elderly patients, good remission.

It really depends on the patient's functional status. If healthy/fit, I would treat with CAR-T. If borderline health/fitness, I would treat with tafasitamab and Revlimid.

I would defer ASCT eligibility to the transplant physician. Personally, this patient's disease appears chemo-refractory.

He is an ideal candidate for liso-cel (or axi-cel, depending on the closest center performing CAR-T), provided he checks all the required boxes for eligibility for CAR-T.

I'd be curious to know what regimen would y'all use for bridging therapy. Tafasitamab + Len looks impressive in terms of durable remissions. I would use Tafa + Len as bridging therapy until CAR-T evaluation. ...

I think it might depend on how long ago the prior chemotherapies were. If relatively remote, some kind of "salvage" (Pola-BR?) then auto transplant would be reasonable. I know this is transformation but if the chemo was relatively recent, I probably would try to get that person to CAR-T ASAP if an option. I wouldn't be thrilled to give another course of anthracycline-based therapy.