How the CAR-T Myeloma Trial Gave Me My Life Back, by Cherie Rineker
Chimeric antigen receptor (CAR) T cells are a living drug. T-cells are a type of Lymphocytes (white blood cells) that identify and remember invading bacteria and viruses. They do this by recognizing markers on the surfaces of infectious or malignant cells. One such protein marker in multiple myeloma is BCMA (B-cell maturation antigen), a highly plasma cell-selective protein. Multiple myeloma is a blood cancer of the immune fighting plasma cells.
Sixty-five months is a long time to be sick. When we get the common cold, we feel crappy for a few days, maybe a week, then life goes on as usual. Unfortunately, this is not the case with cancer. Even when treated with chemo, the disease often becomes resistant to the drugs, and in turn can become even more aggressive than when it was first diagnosed.
Multiple Myeloma made its way into our home in November 2012. It took over our lives and invaded our thoughts, taking away many hopes and dreams. I had to give up the dream of both starting a health spa, and being the kind of wife and mother I aspired to be. Instead, just surviving Multiple Myeloma became my full-time job.
When I was first diagnosed, I remember my oncologist telling me that some people reached remission in just a couple of months. I truly believed that was going to be me. But, more than five years and after over a dozen different forms of chemotherapy later, I had come to the realization that I was not one of those lucky patients. As a matter of fact, I was quite the opposite. I went through those thirteen different forms of treatment at a phenomenal pace and I felt my body slowly decline. Even though all these different forms of treatments had kept me alive for five years, both the cancer and the treatments were slowly killing me. Chemotherapy has made incredible strides in the past decades, but it remains a medicine that attacks cells indiscriminately, destroying both cancer cells and healthy cells. This was evident with the many ER trips we had to make as my body declined and my immune system became overloaded. When, for the thirteenth time the treatment failed, my oncologist recommended that I try a combination of four drugs instead of the usual three, I told him NO MORE CHEMO!!!
About a year earlier, I saw a news program in which a new therapy using the measles virus had brought a myeloma patient, who had run out of options, into complete remission (five years later she remains cancer free). I was intrigued by both the unusual form of treatment as well as its apparent success in achieving complete remission just weeks after receiving it, and it had given me hope. This show introduced me to the idea of immunotherapy and I told my doctor that if this study ever came to MD Anderson, my home hospital, I wanted to be the first one on that list.
Unfortunately, on the day I said no more chemo, a new immunotherapy called CAR-T was not yet available at our hospital and I had to search outside my usual place of treatment (MD Anderson), which had also become my place of comfort. The whole process of locating CAR-T studies and applying to participate in one felt daunting.
Not only were the requirements very specific, most hospitals had long waiting lists and required that I travel, sometimes long distances, to the hospital site just to see if I even qualified for entry into the study. This entire process was made even more difficult by my failing physical condition. By this time both my immune system and my spine were total wrecks, which made traveling a big challenge.
Dana, my good friend and an incredible patient advocate, put me in touch with Brian McMahon, founder of SparkCures, an organization that helps multiple myeloma patients find clinical trials, and by the end of the year we found that a relatively unknown cancer center, Sarah Cannon in Nashville, Tennessee, with a fairly unknown Myeloma specialist Jesus Berdeja, that was doing a phase two CAR-T trial. I immediately contacted Dr. Orlowski, my local oncologist and asked him to write a referral to Dr. Berdeja. I also decided to write him myself. I felt it was important that he not only know me as a patient, with a bunch of lab reports, body scans and an extensive history of prior lines of treatment, but that he also know me as a wife, a mother and a person who had a life that mattered to her children, husband, friends and loved ones. I attached “Dying to get into a Trial”, an article I wrote describing the challenges of getting into a CAR-T trial. I lost a dear friend who literally died while waiting to get into a CAR-T trial. The loss devastated me, and I did not want the same to happen to me and my family. The next day I received a personal response from Dr. Berdeja. He thanked me for my letter and a couple of days later I followed up with his office and was able to arrange an appointment.
Driving to Sarah Cannon takes about fourteen hours from our home in Texas. Though flying would have been easier and much faster, it was out of the question. My immune system was shot and I had a tumor growing on my spine at T12 causing significant pain. My friend and neighbor Amanda, who had lost her son to cancer a few years earlier, was willing to do anything to help me survive mine. She told me that she would drive me back and forth as many times as it took. My husband, wanting to be with me, had to work and take care of our daughter. His work was our only source of income and without it we would lose our health insurance. As much as I wanted him to be with me, it was out of the question. Cancer is horrible at any time in life, but dealing with it while having young children makes it all the more challenging. Amanda is one of the people to whom I owe my life. Without her generous offer to drive me, we may have had to abort our plan. We left early in the morning. The sun would not be up for many hours. I had five pillows tucked all around me, was wrapped in a warm blanket because I was cold all the time, and my chair was completely reclined. All this, together with the opioids I had to take every three hours, made the trip bearable.
Dr. Berdeja saw me the next day and said I would make a good candidate for the trial. I was ecstatic! I thought this meant I was automatically given a spot. When he left the room the research nurse told me that there were more than 30 patients on the list ahead of me. It was hard to hear because I knew I did not have that kind of time. With thirty people ahead of me trying to get into the same trial, it was a long shot that I would get in and I doubted that they would even call me. Very disappointed, we drove home that day and ended up in a snow storm. What was supposed to be a long one-day drive turned into a three-day disaster. Interstate HWY-40, with many more eighteen-wheelers on it than cars, most of which seem to drive well over the speed limit, is an intense highway to travel on.
Add to this the snow that was piled high on both sides of the road, frozen windshield wipers which required us to stop about every thirty minutes to pour anti-freeze over the window in order to see, and the return trip home became a nightmare.
Just a few days after we made it home, I received a call from Dr. Berdeja’s office telling me I could be the next possible candidate if I could be there in two days. Nothing was going to stop me from getting my name on that list! Amanda and I got back in the car and I became Sarah Cannon’s second Phase II Celgene/Bluebird bb2121 CAR-T candidate. I do not know what happened to the thirty plus patients who were in line ahead of me. I know one, my friend, had passed away. Others may not have passed the rigorous qualifications. Some may have gone back on chemo. Dr. Berdeja and I both use my story as an example that no matter how long your shot is at getting into a trial, don’t get discouraged and keep trying. I must mention that I had applied at two other places. One never needed me, and the other did not accept me. For me, what seemed like a hopeless situation just a month earlier, turned into an amazing success story, one I am here to share with you today!
In order to qualify for the CAR-T study, my myeloma biomarker counts had to be at minimum a certain number, my immune system had to be strong enough, and my lungs, heart and kidneys had to be healthy enough to handle the fight that would surely happen once my reprogrammed and re-engineered T cells were infused back into me. In addition, my platelets had to be at least fifty million, a number I had not achieved for many months. Fortunately, when I stopped all chemotherapy, my platelet count rose to the required level fairly quickly. My ANC or absolute neutrophil count was another story. I would not have made it into the trial had it not been for research nurse’s suggestion that I climb the hospital stairs each time the test came back too low. As hard as it was, I was not going to let a couple flights of stairs stop me from getting into the trial. So with Journey’s Don’t Stop Believing blasting from my iPhone, hands and teeth tightly clenched, I climbed the steps of the hospital’s four floors up and down three times. Apparently this would shake the neutrophils off the lining of the blood vessels so they would be picked up in the blood test that would immediately follow. Over the course of one month I had to do this three times. It was this which kept me qualified for the trial, although barely.
After one more trip to Sarah Cannon, my T-cells were harvested early February. This was done through a process called leukapheresis which spins off white blood cells and returns the rest of the blood back to the patient. The procedure required that I have a catheter put in my neck the day prior to the procedure. The harvest itself took only about four hours. Other than some serious tingling in my hands, feet and mouth due to an electrolyte imbalance, something that was alleviated by a calcium infusion, as well as the fact that all my blood was being circulated through a high-tech machine outside the warmth of my body, then returned at a lower temperature requiring many blankets to stop my teeth from chattering, all went well.
After the cells were collected and taken to the lab, a modified form of HIV was used to insert new coding into the gene that makes T-cells. Through the insertion of this new coding, the virus turned my T-cells into a mixture of my genetic code and its own. The new CAR-T cells were now programmed to locate and kill the cancerous myeloma cells by seeking out their BCMA target on the surface of the cell, like Arnold Schwarzenegger was programmed to kill Sarah Conner in the Terminator. Once my T-cells were transfected (the process of deliberate introduction of nucleic acids into the T-cell), they were cultured (pumped-up) and expanded in a laboratory for four weeks where they turned into hundreds of millions of myeloma Terminator cells. We drove back home and had to wait while my army of CAR-T’s were multiplying somewhere in New Jersey in a petri dish.
In the interim, I was put on bridge chemotherapy because my myeloma was growing out of control. Even though the actual number did not look so bad, the viciousness with which these mutated cells were attacking my body was so much worse than they had been five years earlier, when the numbers were much higher! Unfortunately, the chemotherapy did not work. It was a very scary time. In just a short time two plasmacytomas (a plasma cell tumor that grows in soft tissue or on the skeleton) had grown. One was on my sternum and fractured it, making it hard to breath. When I had to sneeze or cough, the pain was excruciating. The other, about the size of an orange, put so much pressure on my spine that I felt as if it had snapped it in half. I ended up in the hospital for twelve days to try and control the pain. Unfortunately pain medicine, even the kind given through an IV, was no match for the pain the tumors were causing. All I could do was lay in bed reclined for those twelve days. I was unable to take showers, walk, and even going to the toilet, which was put right next to my bed, was all but impossible. I was feeling weaker and sicker than ever before. Had it not been for the hope of the CAR-T, I think I might have thrown in the towel. This was no way to live. Thankfully I was given several rounds of radiation, which reduced the pain in my lower back dramatically.
After four agonizing weeks, during which we did not know if I would be able to hang on, the time came for my husband and I to make the long drive back to Nashville. Shawn requested family leave and was granted one week. This time I was leaving for six weeks. We arranged for our daughter to stay with close family friends. Angelina was a real trooper; her Mom was not. I was unable to hold back my tears. The stress, the pain, the opioids, the uncertainty, the fear, it was all too much. I had so much faith in this trial, but I had so much faith in all the treatments I had previously been on, and none of them worked for very long. When we had to say good-bye, I was not sure if I would ever see my daughter again. We hugged and though I did not want to let her go, I knew I needed to and make her feel that it was all going to be okay, that this was not a big deal and that she would see me soon. I saw the concern in her eyes, but she tried to hide it from me, gave me a kiss and ran up the stairs to play with the other girls.
On Wednesday March 7th, I started my three days of lymphodepletion chemo (Cytoxan and Fludarabine). This was required in order to eradicate the leftover T cells in my blood so they could make way for the CAR-T cells. By that time, I had no energy left whatsoever. All I wanted to do was lay around and sleep. I took a blanket with me everywhere we went. I would wrap myself in a blanket when we went to a restaurant, the store to get groceries, and when we were in the hotel, all I wanted to do was lay in bed covered under several blankets.
During infusion of the T-Cell depleting chemo, I needed their preheated blankets on top of my own, all the while my husband sat next to me, comfortable in a T-shirt. When the three days were done, I was given the weekend off and on Sunday I had to check into the hospital and my husband had to go back home. As much as I hated to see him go, I knew my daughter needed him to be there. Five years is a long time for a child to deal with a parent’s illness. She and I were very close. I can only imagine how scary it was for her. However, what she had kept inside since my diagnosis was beginning to come to the surface. She had a lot of anxiety and suffered from panic attacks in school.
We knew I would be well taken care of by the staff at Sarah Cannon, with their very professional and friendly nurses. March 12th the day we had been waiting for finally arrived and I was given back my GMO’d T-cells. Four small bags, pure white liquid inside, were given to me by nurses dressed in blue suits, thick gloves and goggles, those big ones that cover both your eyes and nose. They looked quite daunting, as if they had just walked out of the movie Outbreak, with Dustin Hoffman. Six times they tried to put an IV in my arm for the infusion of the CAR-T cells. Though my port (an access device for patients who need frequent or continuous administration of chemotherapy) was already accessed, the IV was needed in case I had an allergic reaction to the infusion. There was a time when my nurses had loved my veins, they were plump and near the surface, but the three years of abuse prior to getting a port had shot them to hell. Thankfully, when their expert infusion nurse was called in to access my vein she succeeded on the seventh attempt! Life is all about perspective. Prior to my diagnosis five years earlier, I did not like having blood drawn at all! I had only had a couple of IV’s put in my arm during the delivery of my children and back then I thought it was a big deal. Now, every time one of the nurses made a go at it, I would just relax, let out a big sigh, and go with the flow. It was no fun, but it was as it was, and complaining about it would not make it go any better. By this time, I felt very calm, very much at peace. I had surrendered, for better or worse, and trusted my doctor, the nurses, and the trial implicitly. There was no more going back, no changing my mind, so I relaxed and let the process carry me through.
Once the infusion was over it was time to wait. Time for the storm! Time for war! A war of life and death. Death to multiple myeloma! I had watched the movie Lord of the Rings a week earlier. In one particular scene the Elves led by Legolas, prince of Mirkwood and master bowman, fight and kill hundreds of Orcs (ugly demonic like creatures) with bow and arrow. I envisioned my Car-T’s as the Elves, resilient, fast and limber, strong and brave. Multiple Myeloma was the enemy, the Orcs. Slimy, treacherous and vile, they were no match for any of the immortal Elves I had seen pushed into my veins. I know it may sound crazy, but imagining the fight this way, somehow gave it more power, at least to me. By seeing the fight in this way, I became an active participant, cheering my team of Elves on.
I have always been very susceptible to nausea, unfortunately, this time was no different. Several hours after my infusion, right after I ate, I lost my dinner, then my lunch, then my breakfast. The nurse on staff came in and gave me Phenergan, an anti-nausea medicine that always did wonders. Unfortunately, some of my dinner had already made its way into my lungs, and on top of everything else that was about to happen, I ended up with a pneumonia. The next five or six days were rough, but thankfully almost entirely forgotten. To this day most of it remains a blur. That night the war started. I had fevers of over 103F.
This was one of the more common symptoms associated with cytokine release syndrome, caused by the rapid release of cytokines into the blood. My spine throbbed so badly, it felt like it had a heartbeat of its own, and some of my ribs (probably where a previous tumor had been) swelled up which made it impossible to lay down in almost every position. You could safely say that I felt a bit on the miserable side. However, I had no doubt that the CAR-T’s were working. The nurses checked in on me often and I was put on oxygen, primarily because of the pneumonia. I was also given morphine, and though the struggles were real and intense, the medicine I was offered helped me get through the worst.
Two dear friends and volunteers from MD Anderson, Marc and Twilight, were incredibly generous and made the fourteen-hour drive in order to keep me company that first week when my husband couldn’t. I met them during my first stem cell transplant, and we became like family almost instantly. I felt bad that I was unable to be a good host. They drove all this way only to catch me at my worst, and it was not until a couple of months later that they told me about our conversations and the food they brought me every day. Apparently, I was in the worst shape my friend Twilight had ever seen me in, and she did not want to leave me. She thought I could die and she could not bear the thought of me dying alone. Months later I recalled our conversation, me grabbing her hand and assuring her that I would win this fight and for her to go home with her husband. I wanted to put her mind at ease, even though in that moment I was far from believing the words of comfort I gave her.
After almost a week, like magic, from one day to the next, the fog lifted, the pain subsided and the fever came down. I wanted to take a shower, I wanted to eat, and I wanted to go for a walk, though ever so slowly. Over the next week, the walks got longer and I went around the hospital floor many times, iPhone in hand, my favorite songs of the eighties playing. By this time, I could not wait to get out of the hospital as I was bored out of my mind; something the doctors took as a very good sign. Though I still needed four hour antibiotic infusions three times a day for the pneumonia, my oxygen was back to normal and I had more energy than I had in months.
I will never forget the day my husband and daughter came to be with me. It was the last day of my two week stay in the hospital and time could not pass fast enough. All I wanted was to see my husband and my baby girl. I felt as if I had a near death experience and that I walked away from it feeling strong and empowered. If I could handle this, I knew I could handle anything! Finally, the door opened and my daughter walked in with a big smile on her face, closely followed by my husband. We all cried happy tears as we embraced each other for a very long time.
Though my immune system had taken a beating and I needed almost daily shots for that, I felt great. So much so, that on the first morning out of the hospital, I got on the elliptical machine at our hotel. I had not done this in over five years! Every day thereafter, I climbed the stairs to the top floor of the hotel. To think that just a month prior, I could not even bathe myself! My quick recovery felt nothing short of a miracle. During my last visit with Dr. Berdeja, prior to going back home to Texas, he handed me a piece of paper with a big smile. It showed my bloodwork on a graph. The numbers that tracked my cancer had made a sharp dive and were below normal!
I let out a cry of joy and gave him a big hug. During all my years of treatment this had never happened! The results showed what I was already feeling, for the first time since my diagnosis I was cancer free; something my next bone marrow biopsy and PET scan would confirm.
Since that day I have continued to recover and the results have been nothing short of amazing. Today, just a couple of months after I received my genetically modified Terminator/Elf cells, I feel as good and even better than I did before my Myeloma diagnosis. It is funny to think of myself with my CAR-T multiple myeloma obliterating cells. I am genetically modified, or genetically enhanced as I like to say. My husband jokes and says I can no longer go to Whole Foods or the alarm will go off. For a person that was against GMO’s and did not like doctors and medicine very much, I have changed my mind. Today I very much appreciate medicine and science, and I am very grateful for the strides that have been made in cancer research.
Today, five months after the procedure, my immune system still has a way to go to get as functional as it can be. It took four months just for my platelets to get back to 50 million, the number they had to be in order for me to qualify for the CAR-T trial. Then again, if I look at how long my immune system had been bombarded by the cancer and its treatment, four months is not that long. My white blood cells are still below normal, but my ANC, the number that had me climbing the stairs and almost kept me from getting into the trial, is now in the normal range without the help of shots, for the first time in years!
CAR-T taught my immune system how to fight multiple myeloma in a matter of weeks! What two stem cell transplants and thirteen lines of treatment had been unable to do in over 65 months, CAR-T did in less than a month. I don’t like to call myself a cancer patient anymore. I do not say I am in remission. Instead I like to say I am cancer free. Today I live my life like everyone else, and like everyone else, I can get cancer. I hope that my modified T cells will continue to stick around to fight possible relapses, so that it will provide long-term protection.
Where do I go from here? Some people have asked me if I would do it all again, considering how tough the road was. My answer is always an affirmative Hell YES! Sure, the trial was rough, but only for one week. My transplants were comparatively much worse, as were the never ending chemo treatments. However, Myeloma destroyed a lot of my bones, so going back to massage therapy, a job I truly loved, is pretty much out of the question. Sadly, and surprisingly, after we came back to Texas, my daughter’s anxiety grew worse instead of better. It was as if five years of bottled up fear came rushing to the surface. It appeared she had post-traumatic stress disorder and we took her to a psychiatrist who diagnosed her with generalized anxiety disorder and obsessive compulsive disorder that she developed in order to feel in control over what was happening. She is very afraid of germs and getting sick. I continue to reassure her and remind her that it was my immune system that did not work, and that hers is very strong indeed. It seems as if my words fall on deaf ears and for now she needs medicine to help her cope. We are hopeful that her issues will subside as I continue to get healthier. Unless you have gone through what we have, you can’t truly understand how far reaching the ugly tentacles of cancer truly are.
I will continue to bring awareness to multiple myeloma, an often forgotten and unheard of cancer that still takes way too many lives. Awareness is needed for early detection which leads to longer survival and better quality of life. I want to help those who struggle with their diagnosis, who need help when they feel helpless, and give them hope when they feel hopeless. I want to be there for others by believing in them, when they no longer have it in them to believe in themselves. I have been there, I can relate. People always see me with a smile. Despite everything that happened to me, I feel blessed and lucky indeed. I have met some incredible friends on this journey and learned a lot about myself and what truly matters to me. It took a lot of people to get me to where I am today, and I am beyond grateful that I had my tribe of supporters cheering me on along the way. I am well aware that not everyone is that lucky.
As I am editing this article one last time, my daughter and I are ready for a concert tonight. We are going with a group of friends. Over the past years I have had to forego so many milestones, special events and parties. Tonight, I get to go with her and her friends. I will get to be in a crowd and not wear my mask. I will have some wine, and sing and dance along to the music. From now on I will live my life to the fullest, and that my friends, is priceless!
For now, CAR-T therapy is one of the most promising treatments for multiple myeloma and other blood cancer patients. Currently about 20 registered trials are being done in the US and around the world, and sofar the response rates for this treatment have been amazing. Patients in these studies have undergone an average of seven prior treatments before enrolling. Outcomes like the one I experienced could predict the possibility of a revolutionary breakthrough in cancer treatment. It is my hope that CAR-T therapy will change multiple myeloma from an incurable to a curable cancer.
Cherie Rineker, author of A Pilgrimage Without End, How Cancer Healed my Broken Heart, lives with her husband and daughter in South East Texas. She is currently working on her next book, A Pilgrimage Toward Health, Keeping Hope Alive.
This article is an excerpt from A Pilgrimage Toward Health, Keeping Hope Alive, which will be released in 2019.
copyright (c) 2018 Cherie Rineker
You can contact Cherie at www.cherierineker.com