The breakthrough in genetic engineering that lead to two of three patients with bad CLL getting a clean bill of health has generated world wide excitement, with good reason.
It's dramatic, it's a first, it's not chemo, it's mostly drug and big pharma money free , it's a doable technology for CLL that has possible applications for any cancer that can be recognized by its protein markers that protrude from their cell wall (in this case CD19), and it's still working a year later.
My bet is there will be a lot of money to move beyond this proof of concept to phase 1 trials, both at U Penn and other eager centers that can make the requisite designer genes.
That is mostly companies like Amgen and Genentech and a million start-ups, and universities, and big cancer centers such as MDACC, UCSD, Stanford, Dana-Faber, and others.
My bet is that these trials will not be hitting the local oncologists office anytime soon.
My bet is that the demand for this will outstrip the number of openings. It is a very personalized, hands on, and expensive therapy. My T cells won't work for you and vice versa.
My bet is that dosing will be critical as always in Phase 1 trials, but even more so here, where we know we have a very big bomb that can have quite a long fuse. Remember that the onset of the tumor lysis syndrome (TLS), the state where there is a very rapid and dangerous amount of cancer killed in a short time exceeding the kidneys' ability to handle all the debris, was quite delayed in the U Penn trial. Too high a cell dose, and the unpredictable TLS can kill you, too little, and the response is too feeble and the cancer continues to grow.
My bet is that choosing the right target is also critical. CD19, the target in the U Penn trial, is found on all B cells and its precursors, so this therapy wipes out nearly the entire immune army that produces antibodies. Does that mean you are cured of cancer, but may be at risk of dying from measles or chickenpox as the oldest soldiers (the memory cells) die off? We don't know, yet.
Are other targets better and more selective? Will they work as well without the immune risks? Again, that's what trials are all about- to answer these questions.
So what does this all mean to those of us with CLL?
Here's my best case scenario.
It means nothing today.
But I bet (when you have cancer you are always making bets with less than perfect knowledge), that in less than a year we will have limited opportunities to enter phase 1 trials on new iterations of the designer T cell therapies. This is too good a result and way too much fun for the MD/PHDs not to tinker with creating new cells to not work its way through the IRB committees quickly. Most trials will they likely be small and be restricted at first to those at the end of the present therapeutic rope, but as experience and safety data grows, in three years or so, bigger phase 1/11 trials now with pharma money may open for those looking at earlier or even front line therapy.
If all goes great, and and this is a big if, they can find a way to pay for this, we could have a new revolutionary treatment option in less than ten years. Maybe even seven or if a prominent senator is diagnosed with aggressive CLL, five.
That's the Cinderella story. The perfect fitting glass slipper and the lucky girl living happily thereafter.
But it won't be easy choosing what size or design is best, which virus is the safest to do the heavy lifting (the U Penn people used an HIV like virus with its reproduction genes disabled), what cancer center is best ready to handle possible TLS weeks out, what dose of T cells, what chemo if any is needed to clear the table before the gene therapy can begin, and a thousand other unknown unknowns.
So again for us patients, the trick is to stay alive, try to keep our powder dry by avoiding therapies that damage the marrow or immune system as long as possible, keep our ears to the ground for new research, assess whether we really need to do anything so don't get caught up in the hype and pressure and worry that we might miss the boat if we don't jump at this, and if we do need therapy, is what is available in a gene trial therapy the best choice?
The good news is that when we do need therapy, the choices are getting both better and tougher.
The devil we know such a FCR or Revlimid or Bendamustine or HSCT, or the devil that we are just getting to know such as the new small molecules such as CAL101, PCI 32765, ABT99 and more and more sharply focused cancer pathway blockades, or the completely unknown devil with his great promise, the new very sexy new kid in town - designer T cell therapy?
An exciting time for sure. I love these possibilities, but that is what they are possibilities. But so was Gleevec at one time.
For me, I am nervous about jumping too fast until I see more data, especially long term safety data. I am frightened that I will be, as Leonard Cohen said, "torn by what I have done and can't undo." Still the appeal is undeniable- the benefits of an allogenic transplant with much of the downside taken out of the equation.
So I plan to stay alive and follow my own advice given above.
But first I am going fishing in Missouri. And I don't even eat fish.
Labels: Breakthrough, decisions, T cells