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CAR-T therapy is indeed very cool and very promising against certain lymphomas. My wife had triple-hit DLBPL (rearrangements of the c-MYC, BLC-2 and BCL-6 genes) and received CAR-T therapy. The therapy itself almost killed her due to neurotoxicity and other immune responses. We were initially very optimistic as the CAR-T cells rapidly destroyed the cancer cells and visible signs of the cancer on her body vanished. The cancer is her brain was eliminated, but after a few weeks, the lymphoma in her body came raging back, causing pleural effusion, swelling and horrible pain. Keytruda (pembrolizumab) was started as a salvage therapy but wasn't effective. Time of diagnosis to death was 10 months. CAR-T was administered in the middle of July and Melanie died on the first of October. For those wondering, she received several rounds of DA-EPOCH-R chemo for the lymphoma, high dose methotrexate for the CNS involvement, had a port installed in her chest and an Ommaya on her skull that allowed drugs to be put into her brain (intrathecal treatment.) The first rounds of chemo were pretty effective and she had a few good months. The brain involvement eventually damaged some nerves which caused Bell's palsy, which causes eye droop and facial paralysis. It sort of looks like the results of a stroke. For those curious, the CAR-T therapy itself was $650,000 US. Getting the blood to create the T-cells involved yet another special catheter getting put in to do the draw. The CAR-T infusion was a big deal at the cancer center; lots of staff came by to observe. It was also super stressful for Melanie and everyone as there was a pretty fast reaction to the infusion. She ended up in the ER about six hours later and was in the ICU for about a week. One thing I do wonder is if some of the drugs used to moderate the CAR-T cell expansion slowed things down enough that some of the cancer was able to avoid the T-cells? Regardless, if things weren't slowed down, she would have died from the infusion. |
Your thought about the drugs maybe limiting the effect of the CAR-T is an interesting one and the subject of ongoing investigation. One common drug used for CAR-T related cytokine release syndrome, tocilizumab, does not appear to have negative effects on CAR-T proliferation or efficacy. However, it doesn't seem to do as much for neurotoxicity (which seems to be a separate mechanism from the cytokine system), and they often have to resort to steroids for that. Steroids do dampen T-cell activity, but to what degree that impacts CAR-T effectiveness is not clear. However, as you mention, sometimes you are left without much choice.