7 Months Now

Still no sign of disease, beta-2 microglobulin down to 3.83 and falling, lymphocyte count has crept into the normal range. We’re stretching the Tecvayli dose interval to 3 weeks to give the T-cells a bit of a break.

Biggest news is I got a dramatic result from myringotomy tubes. If I’d known they were an adult option I would have done it sooner.

Still More

The cold persists, sometimes goes to bronchitis then gets better, then… Nancy’s tired of having to shout to be heard.

I need an immune system, will discuss radical/crazy approaches with the oncologist next month if things don’t get better.

Meanwhile, beta-2 microgolbulin is creeping up but there’s no other sign of any myeloma at all.

Day More

Still no evidence of myeloma on blood tests or PETT scan. Also almost no evidence of an otherwise functioning immune system – still fighting the cold I picked up on Memorial Day. Things were bad enough that we cancelled at the last hours our trip to the Dillon, CO, String Cheese Incidents because it wasn’t clear I would be able to handle the altitude. Still hoping to make Eugene, where it’s 30 degrees cooler than Tempe, and have arranged to get a Tecvayli dose there (with an oncologist who’s looking forward to seeing his first patient on the drug).

Day Many

Labs yesterday show continued low tumor markers, many undetectable, and slightly improved renal function (Cr 2.03). PETT/CT scan next Monday will presumably confirm little activity. I’ve had nearly four weeks of likely viral bronchitis that just won’t go away, so the oncologist was quite amenable to stretching my dose interval on the Tecvayli to every other week, and halving the associated dexamethasone dose. We’re working on coordinating with Oregon Health Sciences University to get some doses up in Portland rather than having to fly back home quite so often. All in all a very good visit. The Dillon Cheese Incidents have an ADA section that is significantly less crowded than the rest of the venue, and there’s a mid-venue seating section for the Eugene show that’s also a bit more distanced than the usual mosh pit. My life’s not as narrow as the Covid lockdowns tried to make it, but I do need to be careful.

Day 47

We’re far enough down the road that yesterday’s labs are worth reporting, with generally good news. Hgb is 11.8 without EPO, and Cr is down to 2.12.

Free light chains, which were quite low after the 4-drug bridge therapy in October, are now undetectable. We’re waiting on the M-spike but it wasn’t much, either. Beta2 Microglobulin, a marker that was normal all the years prior to the September relapse, but went up to 5.3 even after the bridge, is now down to 3.8. It looks like Tecvayli is working, which (again) puts me on the good side of the 50% response rate. Some responders relapse quickly, others last quite a while. There are also other bispecific antibodies in the pipeline that could well come available before I need them. My renal function excludes me from most research protocols, but the pretty good response to the bridge suggests this new clone is more sensitive to conventional chemo than previously, so if I need a little extra time there will be options.

Next month we’ll discuss stretching the dose interval to something longer than every week, which would really help with travel. Meanwhile, it does look like I can get doses up in Portland when we’re in Oregon.

Day 10

A little bit of headache with a drop in temperature this afternoon resolved with some fluids. No other signs of CRS or anything else for that matter. We anticipate a minor moment of truth tomorrow or the next day, but I suspect the toci will pretty thoroughly mask any trouble, if any.

We are told the occurrence of CRS after the second dose is not predictive of any more such events. Some 90% of previous patients had at least one mild bout of CRS – some after the first dose, many more after the second, a few less after the third, and very few thereafter. The N of the study and subsequent experience are still not high enough to draw a lot of conclusions. However, reason, and some limited experience, do suggest that the presence of a reaction is a good sign that *something* is happening. This is a great comfort to those of us whose greatest fear is that the treatment won’t work.

Day 9

(Posted a day later)

A somewhat eventful weekend. I got the second step-up dose on schedule Day 4 and was fine until Sunday (Day 7) early afternoon when I began to feel a little off, with mild headache, mild increase in my normal tachycardia, and a temp of 99.8. A dose of Tylenol fixed everything, but when I confessed at the next checkin time the on-call Doc said he didn’t want me masking CRS, so by evening things returned with an increase in my baseline tremor and now temp to 100.9 so it was time to be admitted. The fever broke with some fluids and antibiotics but it was clear I wouldn’t be getting the final dose the next morning.

Day 8 dawned with no symptoms but HR still 120s, so they went ahead and gave me some tociluzimab (an IL6 blocker) which worked rather quickly. They would have let me have Tylenol, too, but it wasn’t needed. The NCAA basketball final game was the sole salvation for an incredibly boring day.

Day 9 (Tuesday) the team came on rounds, reported all my cultures had come back negative, and offered me two choices: 1) get the dose right now and spend the night, or 2) go home now and come into the outpatient unit for the dose, delaying everything yet another day. I opted for 3) dose now, discharge after the obligatory 2-hour observation, and follow up as normal with the outpatient crew. My reasoning was that, especially with the toci on board and the previous CRS experienced only after the dexamethasone premed wore off, any problems if any weren’t going to crop up until Thursday at the soonest, so spending the first night in the hospital wouldn’t accomplish anything. They bought it.

Day 2

The homeopathic dose was uneventful. I survived the Benedryl premed because they let me have some lorazepam to keep me from jumping out of the bed. Total boring time about six hours because we waited for labs to come back, then IV start (for just in case rescue), then two hours observation. Next dose day I’m bringing lunch.

Mayo is pioneering at-home monitoring instead of admission for observation. We have a tablet, with a NIBP machine and pulse ox bluetoothed in and a SIM card connection to the Mayo Cellular Therapy floor. Five times/day we take vitals (have to enter oral temperature manually), then speakerphone into their hotline for a mental status exam that includes Nancy relaying how well I perform simple functions. Finally, the nurse gives me a sentence to write and we message them a photo of the result. My handwriting and fine motor function took a hit all by themselves about six months ago, so I’m a bit shocked at the results, but they’re only looking for further deterioration.

Since one of the checkin periods is 23:00-MN I may be doing more updates like this before I can fall back to sleep. Especially with the dexamethasone premed on dose nights and the night after. Wish me luck tonight…

Day -4

Well, once again it appears disappointment has resulted in what is probably a preferable alternative. A mandatory step in CAR-T protocols is lymphodepletion with conventional chemotherapy (Cytoxan/fludabarine) prior to the reinfusion. Last time around it took a good 6 months for my bone marrow to mostly recover, and it seems plausible to me that the qualification “mostly” is the reason for the “out of spec” designation (nobody here knows if that means insufficient numbers or insufficient activity) for my newest CAR-T cells. I’m not the first Mayo Carvytki recipient to have this issue. Avoiding that hit is itself alone perhaps a good reason to choose a bispecific antibody over CAR-T, so, again, the Mayo’s CAR-T expert seemed pretty happy to recommend the switch now that they’ve finally ramped up the Tecvayli protocol for several weeks now.

On Day 1, March 27th, I will receive a tiny SQ dose. The Mayo experience already has been that daily outpatient monitoring is sufficient to detect the expected mild Cytokine Release Syndrome or neurologic toxicity, most of which can be treated from the clinic. My relatively small tumor burden and low lymphocyte count (thanks a lot Cytoxan back in September) might well predict milder toxicity anyway. If all goes well on Day 4 I’ll get a small dose with further monitoring. The first full dose comes on Day 8, repeated every week after, with the option of dose adjustment if there are any problems (unlikely after day 15), something that is harder to do with CAR-T. We should see some response by the second month. The great concern from then on would be infections, but I won’t really be much more immunosuppressed than I’ve been since 2019.

Again, because we’re still targeting BCMA the chance of success is probably only about 50/50, but if we just buy a few months of response there are other bispecifics in the pipeline targeting other antigens on the myeloma plasma cell, with FDA approval possible by summer, even if I lack sufficient renal function to get into research protocols. I am again cautiously optimistic, which was an attitude difficult to maintain the last several months.