Originally published in "Discussions with Don S. Dizon" on The Oncologist
In oncology, we strive for cure, and short of that, we strive for stability. In some instances, particularly with recurrent disease, cure is rare, and the process of curative treatment can be quite extreme (for example, bone marrow transplantation for recurrent lymphoma, where the real risk of graft-versus-host disease is substantial and, in its most extreme, debilitating). But in solid tumor oncology (for the most part), we have been driven towards less toxic treatments, less complicated regimens, while continuing to strive for better survival.
With immunotherapy, we have seen such strides realized. First in melanoma, then lung cancer, then kidney cancer, and with each year, more and more indications seem to emerge. CTLA-4 and now immune checkpoint inhibitors have revolutionized cancer therapy, expanded ways to treat a number of cancers, and induced remissions where we once had no realistic shot or hope for this. Yet hidden in the headlines, and perhaps not as well publicized (due to our collective enthusiasm to see just where the field can take us next), is the reality that these treatments can be toxic, in some cases debilitating, and even life threatening.
Such was the case with Julie*. I had met her 3 years previously, when she was seeking a second opinion. She had been diagnosed with an extremely rare and often fatal cervical cancer. Her primary treatment consisted of chemotherapy with radiation, after which she had received a “novel” combination of three chemotherapy drugs. At the age of 19, her doctors wanted to give her the best chance of survival. Treatment was tough on her, and her bone marrow just barely withstood therapy. Months after treatment, she would require multiple hospitalizations for abdominal pain, attributed to late complications of chemoradiation. Still, she remained disease free for 19 months, and for the most part, returned to an “almost normal” existence, as a college student, office worker, and cherished sister and daughter. That is, until a surveillance scan showed new adenopathy in her chest. She was asymptomatic, but a biopsy confirmed the worst—she had developed metastatic disease. When she saw me, she was devastated. She knew the statistics well—that on average, women like her with this cancer lived on the order of months, not years. She cried for most of that first visit, and I felt horrible for her. It made me want to give her the best chance I could think of.
At the time, immunotherapy was still so new and promising. Several trials were underway exploring these strategies across all tumor types. I was aware of responses, and sporadic remissions that had resulted.
“Let’s see if I can get you a PD-1 inhibitor,” I said. “Your cancer is so rare, and there are no approved strategies. Maybe we’ll get lucky.”
I applied for an off-label exception to use a PD-1 inhibitor with her insurance company, and to my pleasant surprise, they approved a 6-month course of therapy (apparently, her young age, dire diagnosis, and lack of treatment proved to be an effective argument!). We commenced therapy and I was surprised at how well she tolerated it. She was thrilled to keep her hair and was relieved that she did not have any issues with abdominal pain.
At 6 months, we repeated her scans. To my astonishment, her disease was gone—she was in remission. I practically ran in to her examination room to deliver the news, and I still recall how she screamed with joy, laughing and crying with her mom over the incredible results.
Unfortunately, her joy was short lived. She was admitted the following week with fevers and excruciating abdominal pain. She was unable to eat and her abdomen had become acutely distended. Repeat scans showed diffuse bowel wall thickening and new ascites. The rapidity of symptoms was consistent with inflammatory colitis, though we had yet to determine if it was infectious, immune mediated, or both. She continued to decompensate in the hospital, which prompted an urgent operation where part of her colon was resected. While no tumor was present (at least on visual inspection), her surgeons were concerned because her bowels were so fragile. She ended up hospitalized for 7 weeks. At discharge, she weighed a fraction of her baseline and looked sicker than I had ever seen her.
It would take months before she felt like herself, but in the meantime, she suffered. Her bouts of abdominal pain landed her in the hospital several more times, and she needed increasing amounts of narcotics to get it under control. Slowly, she lost control of her life and the future she had planned—she could not stay in school and eventually had to move home. At her last visit we decided to repeat her scans in order to re-evaluate her bowels and to see what the cancer was doing, since it had been months since her last treatment.
To my shock, she was still in remission—there was no sign of active disease. Her bowels, however, still looked a little dilated and the ascites persisted. Ultimately, we felt this was immunotherapy-mediated colitis on top of chronic complications from chemoradiation. I explained the situation as best as I could, apologizing for how much she had gone through. She only had one question, though: “When will I feel better?” It proved to be the one question I could not answer.
Even now, I could not predict that she would get so sick, any more than I could have predicted her remarkable tumor response to immune checkpoint inhibition. Her life was irrevocably compromised due to treatment. I had hoped to give her the promise of a future, of life without cancer, and in a way, I guess I did that. But, is the price ending up too high to bear? Only time will tell.
*Details changed to preserve anonymity.