Ibrutinib stopped working for Dr. Matt

George, Matt, and I began the National Institutes of Health clinical trial with ibrutinib (PCI-32765) the exact same day. We decided we are blood siblings. George and Matt will be forever my “blood bruthas.”

Ibrutinib is now called “Imbruvica” and is available to cancer patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Soon the FDA will approve it for 17p deleted CLL/SLL cancer patients.

My last visit to NIH in Bethesda, Maryland was in October. I had hoped to meet up with George and Matt, but I did not hear back from Matt. I thought that either he was a poor communicator or something was wrong. Well, something was wrong. This is what Matt emailed to me:

Hi La Verne and George,

I’m sorry I’ve been out of touch, but I had a dramatic reversal of fortune in late September through October and was unable to communicate well. 

In summary…My June 2013 ibrutinib checkup went beautifully, with what they called a complete response to the experimental drug.  There was no sign of CLL in my bone marrow biopsy and only 2-3% of my blood cells were CLL compared with about 90% CLL when I started the NIH trial.  All was looking rosy and very positive. 

               On my 15-month checkup on 27 September 2013 things changed.  My white cell numbers were up a bit, but the NIH team was not concerned at that time.  They said they had seen some fluctuations like that and not to worry.  However, they wanted me to get another blood test sooner than the usual 3 month test, so I went to my primary care physician a couple weeks later and found that the white cells had doubled in just under two weeks. 

               The NIH team asked me to visit again on 16 and 17 October for further testing.  At this point they confirmed that the CLL had “broken through” the ibrutinub treatment and that the drug was no longer working for me.  Such a promising start turned in a total bust by mid-Oct 2013.  They suggested I return to Dr. Michael Grever and the rest of the OSU team in Columbus, OH for alternative treatment. 

               I saw the OSU team on Friday, 25 Oct 2013, and got some options for alternative treatments.  That is the day my time with ibrutinib stopped and I was no longer on the NIH trial.  We were planning to begin the new treatments at OSU soon after, but I had a series of major complications that led to three hospitalizations, two for two days each by my home and one for four days at OSU.  I retrospect all the troubles and pain were due to a Richter Transformation of my CLL into a very aggressive large-cell lymphoma.  So I turned into an even more complicated case than I could imagine.  The other thing the OSU team said is I have many more mutations than most people, making things very complex. 

               Below I have copied my latest upates to family and friends.  I’ll ask that you two distribute this to the NIH trail group as you see fit.  Ibrutinib worked well for me for quite a while, but then it stopped.  I think my case is unusual, so everyone else should stay encouraged. 

               I’m sorry I won’t be seeing you at NIH anymore.  It was great to have you in my cohort!

               As always, I wish you all the best with ibrutinib and hope all continues to trend well.  I’m taking it one day at a time, using a tremendous network of family, friends, and colleagues in Hiram and beyond.  Enjoy each day and worry about nothing but having fun! 

All my best to you both and the rest of the NIH crew,

Naturally Yours,

Matt

As I mentioned in my previous posts, Ibrutinib is a BTK inhibitor. That means it blocks a pathway used to develop leukemia cells. In Matt’s case the drug stopped working, because the leukemia found another pathway and then transformed into a very aggressive Richter’s transformation -- large-cell lymphoma. This affects about 5% of CLL/SLL patients at some time. It can appear suddenly, even to patients in remission. It has a poor prognosis with survival of five to eight months, according to the experts.

In summary Matt is at Ohio State University in another clinical trial with another experimental drug (IPI-145), an oral inhibitor of phosphoinositide-3-kinase (P13K)-delta and P13K-gamma. Matt said that the new drug is not a cure but rather a stopgap measure to get the aggressive disease under control.  

The only way he will be cured of all this is through a stem cell transplant (aka bone marrow transplant).  Unfortunately he has no matching donors in the system.  The medical team is looking into using umbilical cord stem cells or using a half match donor. No transplant can happen until the lymphoma is under control. Anyone with a fully matched donor and who has the cancer under control is in the best situation for success. Matt will be my guinea pig so that I know what to do if the same thing happens to me.

I got this news about Matt at the time I came down with an upper respiratory infection with laryngitis. I also had a severe drug-related cramp in my right ankle which tore my ligament. So I was hobbling around with a brace and cane, but the most difficult part was not talking. LOL. This is a ripe setting for a pity party. Lucky for me my friend Sally was visiting from Santa Barbara/Houston and there was no time for anything but laughter. Then Carl and I visited our friends Janis and John and the laughter continued.

Then on Thanksgiving my children and my baker’s dozen grandchildren came over to share our turkey dinner with Carl and I. That is when I was reminded again how very blessed I am for every single day.

I have kicked the pity party to the curb.