Nivolumab, pneumonia and venetoclax!
“Life is a crooked line. It’s rarely what you plan.” –Chuck Slaughter, founder of TravelSmith
Or, as I’ve quoted many times before in this long story, “If you want to hear God laugh, tell Him your plans.”
Indeed, my life and plans have not been a straight line. I have settled in several times to write an update to my story, only to have our plans change…over and over again in the past six months. I will try to tell you of all these permutations of our plans in a somewhat condensed form, but those long-time readers of my stuff know that it is hard for me to tell stories succinctly. I always seem to render them in excruciating detail. I can’t help myself. Hey, I diagnosed myself with “hypergraphia” several years ago. I guess it doesn’t heal itself!
Last January it looked like I was relapsing. The folks at M. D. Anderson made plans for me to get a huge number of tests and to return in a month for follow-up. And indeed, on my return a month later, the manifold tests showed that I was indeed relapsing, that I was failing my wonder drug, ibrutinib. I’d long known that it was possible to relapse on ibrutinib, but I had done so well for so long, I was thinking I’d have many more good years on this drug. I knew of some folks who have been on it five years or more and continue to do well. I’d hoped to be one of them.
But, since I was relapsing, we had to come up with a plan for my next treatments. I mentioned at the end of my “Book Five” that Doc Keating was considering trying the checkpoint inhibitors on me. To that end, I was signed up for a clinical trial which combined the ibrutinib with a checkpoint inhibitor called nivolumab (trade name Opdiva) which is already on the market and shows success against lung, kidney and melanoma skin cancers. It had not, however, been used against leukemias except in a very few small trials. But it looked promising.
In February, I signed all the appropriate paperwork usually associated with clinical trials (laying out all the known and unknown risks). I also was scheduled for a whole raft of new tests to make sure I was eligible and qualified to be in this clinical trial, for which you have to be sick enough, but not TOO sick, to get in. The tests, which were scheduled for early March, included about a dozen tubes of blood being drawn, another bone marrow biopsy, CT images of my abdomen, chest and head and neck, an EKG and, finally, a cardiac echogram. I believe just getting eligible for the study set my insurers (the taxpayers of America—thank you very much!) back about $10,000 or so. All the tests went well so I was scheduled to begin the trial, which was the nivolumab in combination with my recently failed ibrutinib, later in March. But let me digress for just a moment in telling this story.
Initially I had great interest in getting into the nivolumab plus ibrutinib study. It sounded exciting (any drug that can help you stave off certain death HAS to be exciting, I think) but the more I thought about it, the less I liked the idea. I could find close to nothing in the medical literature showing that nivolumab had significant effects against CLL cells, and I knew already that my CLL cells weren’t responding to the ibrutinib any longer. “What was the point,” I thought to myself. But, I was scheduled to begin the study at the end of March and we went forward with the plan.
Then the trajectory of our plans went sideways. Our family had a long-planned trip to Alaska set up for mid-March, just before the start of the “nivo” study. We were headed to Fairbanks, the better to see the Northern Lights, plus we had plans to go dog sledding, snow-machining, flightseeing and more. We had a wonderful time up there as I mentally prepared myself for the upcoming study to start.
But, as we flew home from Alaska, I developed a fever. Followed by shaking chills. Followed days later by a persistent and vicious cough. I thought I had a bad cold. After about ten days of this, it was time to go back to Houston to start my new trial. There I saw my nurse practitioner, Jackie, who asked some questions and listened to my chest for a few seconds. “Do you want to be admitted?” she asked. “Hell, no!” I responded. I still believed I had just a bad cold and maybe a little post-viral bronchitis. But Jackie ordered a chest X-ray. It showed “double pneumonia,” pneumonia in both lungs! When the X-ray results came back, Jackie told me-- didn’t ask me-- “You’re getting admitted!” They ended up growing both the bacterium Pseudomonas and the virus human meta-pneumovirus out of me.
And so it was that I spent April Fools’ Day on the 16th floor of the M. D. Anderson hospital wing. Unlike the long-ago April Fools, who were celebrating New Year’s Day in April, not yet having heard about the change from the Julian to the Gregorian calendar, I knew the correct date. I just didn’t know when I’d be able to start my new study drug, the “nivo”. I was sick enough that it couldn’t be administered, but I really wanted to get going with something. I could feel lymph nodes in my neck and underarm areas growing, seemingly on a weekly basis.
But the study was postponed while I was tied to a hospital bed with an IV pumping in industrial strength antibiotics I’d never heard of before (ever hear of linezolid or cefepime?). I spent four days on the ward and then another five weeks on various oral antibiotics, trying to get well enough to start up the trial of nivo. All the time I was impatient to get going on the study. My nodes were getting bigger all the time and aching daily.
Then the trajectory changed again. I went back to M. D. Anderson in early May to see Doc Keating to see if I was finally well enough to start the study. We were running out of time, as the cluster of tests I’d done in early March were going to “expire” after 60 days and those days were about used up. But, Doc Keating wasn’t there. He was out recovering from back surgery, having been involved in a freak incident. As I hear it, there had been a car fire in the hospital parking garage and someone, driving too fast to get away from it, almost ran Doc Keating down. He dove out of the way, injuring his back and ended up requiring surgery.
So, instead I saw his protégé, Dr. Phillip Thompson, another Aussie who specializes in CLL and who is being groomed to take over for Doc Keating. Doc Keating is now working part-time and is slowly, very slowly heading into retirement. It was great to meet Doc Thompson after having only heard about him from other patients lately. If you see any of the patent Power videos concerning updates in CLL, you’re probably seen a lot of Doc Thompson in recent months.
Dr. Thompson examined me, felt the enlarged nodes in my neck, under my arms and in my belly (he could tell they were there though I could not) and we talked about the nivo study, for which I was still signed up. But Doc Thompson said that the early results of that study weren’t encouraging, that the response rate wasn’t very good. He felt that it was disappointing that they weren’t better, because in theory the nivo should be a great treatment for CLL. But, since it wasn’t working out well, he suggested I enter into a study of another drug called ABT-199 (also known by its generic name, venetoclax).
I’d been hearing more and more about venetoclax lately and in fact, knew that it had been approved for certain CLL patients just the month before. It’s been in development for about as long as ibrutinib, but some early problems in its testing phase set it back. This stuff really works! It works, maybe, too well in some cases. There were a few deaths of some patients early on because this stuff kills off CLL cells so fast that the cellular debris and the inflammatory chemicals in the CLL cells overwhelmed some folks’ kidneys and immune systems in a condition called “tumor lysis syndrome.” It’s nothing to mess around with.
I was happy to hear that I could sign up for a venetoclax study. I had actually wanted to get into one the previous February when I signed on to the nivo study, but there were no venetoclax studies open at the time. I knew it was a wonderful drug for CLL and I also knew that the docs administering it were exceptionally careful in giving it now, knowing full well the deadly complications it could bring on. And so I signed on to the study.
Only then did I go looking for recent updates on the drug and folks in my condition. You will remember that I have the deadly 17p chromosome deletion and I also now have failed the ibrutinib after more than three years. I looked up recent studies of folks like me who were taking venetoclax. There was one such study. It flatly stated that patients who have this chromosome abnormality AND who have failed ibrutinib have a “dismal” prognosis. They had recently started a study using venetoclax on some of these patients. At the time of publication they had signed up 18 study patients. Four of them were already dead six months into the study. And, the overall response rate was said to be about 60%. That left 40% of those patients with little hope. That scared me. It really scared me. So, as I entered into the study I wondered if I’d be one of the lucky 60% who at least showed some response to this drug, which apparently was now my last and best hope for survival, or whether I’d be one of the 40% for whom there would be little hope.
--Next; slowly and carefully starting the venetoclax…and maybe a transplant?
“Experience is the comb that life gives you after you’re bald.” –Chinese proverb