A Cancer Patient’s Experience With a Rare But Serious Adverse Event

I was diagnosed with B-cell follicular non-Hodgkin’s lymphoma in 2007. I initially received rituximab immunotherapy and chemotherapy. After a few years of remission, I had a relapse and received rituximab and bendamustine. In late 2016, I had an aggressive relapse. Because my disease was refractory to rituximab and chemotherapy, my oncologist recommended bone marrow transplant. I was reluctant to do it. I also was ineligible for Chimeric Antigen Receptor T-cell (CAR-T) therapy, because the label specified transformed follicular lymphoma. Then my oncologist prescribed lenalidomide, a drug used for certain types of hematologic malignancies. The drug was sent to me by a specialty pharmacy, and I had a telephone consultation with their pharmacist. This focused mainly on the risk of embryo-fetal toxicity and other black box warnings. From the information I received from my healthcare providers and other patients, I got the impression the drug was generally well tolerated. After I received the medication, I did read the black box warnings on the package insert and skimmed through the medication guide; I felt most of the important information had been communicated to me by the pharmacist.

After 2 to 3 days of taking lenalidomide, I noticed a neck stiffness and tightening of my scalp. I also felt swelling of my face. I initially did not consider it serious, and since I had an appointment with my oncologist in a few days, thought I would mention it then. But, the next day these symptoms worsened, and my eyelids were swollen too, so much that I had trouble inserting contact lenses. I then did an Internet search to see whether other patients have reported these side effects. I did find discussion on these symptoms, and that in some cases the patients mentioned their physician had stopped the drug. I worked as a medical writer and at this point, it occurred to me I might have angioedema. I checked the package insert and found angioedema mentioned as a postmarketing experience. Further, it was an adverse event (AE) that required discontinuation. I decided to discontinue, having taken 4 doses in all. I sent a note to my healthcare provider to that effect adding that I suspected angioedema. When I saw my oncologist a few days later, he noticed my facial swelling and agreed with my assessment. My symptoms resolved. In late 2017, I had radiation treatment that worked extremely well.

I later thought about how I handled this situation. I worked as a medical writer and had been an editor of drug databases, and was aware how serious AEs can be, and of medication guides. Yet as a patient faced with the prospect of having to discontinue a potentially life-saving drug that could be a last resort, knowledge took a backseat to denial and wishing that I could continue taking the drug. I went to the Internet with the hope that I would see reports that others were able to continue despite these side effects, and that these side effects subsided. Also, I did not want the generalized, impersonal information of the medication guide but rather actual patient voices. I realized I made the mistake of not contacting my oncologist or a pharmacist with my side effects right away. Partly because the AEs were uncomfortable but did not particularly interfere with my daily activities. Also it is not always possible to contact healthcare providers immediately.

I did a literature search and came across a study which, albeit comprising a small number of subjects, suggested most patients do not read risk information; a chief reason was patients felt they were already familiar with the necessary information (1). This was the case with me, the lenalidomide medication guide was long and wordy, the first few pages dealt with basic information that I had already covered with the pharmacist so I felt I knew all that was there to know. The warnings regarding serious side effects such as skin reactions and swelling of the face were buried deep inside and described in only a few sentences. This may be due to the rarity of these events. Further, the medication guide did not include words like edema or angioedema, nor did it describe all the symptoms associated with it like neck stiffness or scalp tightening, so a search with those terms would have yielded nothing. I did not recall these side effects mentioned during my consultations with my health-care providers either. In fact, my oncologist was initially somewhat skeptical of angioedema because it is so rare.

My experience suggests there remain unmet needs in educating and informing patients when it comes to rare but serious AEs. As a patient, I was scared and emotionally fragile and focused more on controlling the disease than on an AE that wasn’t very debilitating and more like a nuisance. While in my case I found patient experience on the Internet valuable, it is not always a reliable source. Understandably, given the restrictions of time, pharmacists and physicians may not always cover every rare but serious AEs during consultation, especially when more critical risks are involved. It is also not feasible for them to regularly check on patients. However, if rare but serious AEs that necessitate immediate medical attention are emphatically mentioned by healthcare providers during initial consultation, it may help patient awareness. The medication guide and safety information documents may also display rare but serious AEs earlier in the text and more prominently to catch the eye of the patient. In addition, since patients are going to use the Internet for information, the medication guide may provide detailed descriptions of symptoms with terms that patients may use to search online. Finally, if an informal quiz can be included in patient information materials that focuses on all AEs, with healthcare providers encouraging patients to take the quiz, it may also prompt patients to read the medication guide more thoroughly. I would have enjoyed the personal challenge of a quiz. I have read there is a drive to make medication safety more patient centered; quality of communication and engagement have been mentioned as measures (2), and these are some ways communication and engagement may be proactively improved. I have learned from my experience, but also realize that had I taken the medication for another few days, it may have resulted in severe harm, and these are some factors I feel could have made me more aware and act more promptly.