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S. Vincent Rajkumar, MD

Failing to get into medical school is a setback; failing to respond to myeloma is not the type of failure I could have possibly rebounded from. And here was Charlie, happy and peaceful amidst the worst possible situation.

—S. Vincent Rajkumar, MD

The following essay by S. Vincent Rajkumar, MD, is adapted from The Big Casino: America’s Best Cancer Doctors Share Their Most Powerful Stories, which was coedited by Stan Winokur, MD, and Vincent Coppola and published in May 2014. The book is available on and

It was August 1999, and I was barely 2 months out of my fellowship training. One of my first patients was Charlie, a 58-year-old man with newly diagnosed multiple myeloma. Accompanied by his wife and two adult children, Charlie had traveled hundreds of miles to be seen at the Mayo Clinic. His was not a straightforward diagnosis, since there were several atypical clinical features.

One of the advantages of working at the Mayo Clinic is that it gives you instant credibility. Even though I was literally just starting my career, I was seeing patients from far and wide, most seeking a second or third opinion—perhaps a more optimistic one than they had been given at home. But this was a burden as well. Patients had great expectations, and seeing a newbie oncologist for an incurable cancer is not why people fly across the country. Further, I usually had very little to offer. Multiple myeloma was a disease for which we’d had no new drugs for nearly 4 decades.

I hesitantly introduced myself to the crowd of hopeful eyes and held out my hand to the patient. Charlie gave me an enthusiastic handshake that practically broke my hand. He was bright, cheerful, and full of hope. I started to wonder whether he knew what the diagnosis was. However, within the next hour I realized that Charlie was well aware of what he had. He knew that myeloma was a devastating, incurable malignancy. He also knew that treatment options were limited and that we had very few drugs that really worked.

The Resilience of Patients

Over the next 2 days, I confirmed the diagnosis and explained the various treatments available. I told him that since he was relatively young, stem cell transplantation was an option. I also told him that we were starting clinical trials with thalidomide (Thalomid), a notorious teratogen. In the 1950s, thalidomide, prescribed as an anti–morning sickness treatment for pregnant women, caused thousands of birth defects, the most prominent one being malformed limbs. It was now being tested as a possible new treatment for multiple myeloma.

I was hoping that I’d lay out some options and he’d pick one. Instead, Charlie said he trusted me completely and was going to do whatever I recommended. I hurriedly excused myself and went out to discuss the situation with my senior colleagues who specialized in myeloma. I returned, a bit more confident, and after a lot of discussion, enrolled Charlie in the thalidomide clinical trial.

We talked about my 1-year-old son, whose picture he saw on my desk. What I mostly remember is that we had a lot of laughs and warmth. As Charlie and his family departed for home to initiate therapy on this promising trial, I actually felt more confident in my step that day.

A little over a month had passed when I received the call. Charlie’s myeloma had progressed on the thalidomide therapy, and he now had a spinal plasmacytoma with impending spinal cord compression. He was being rushed into radiation therapy. I was sick to my stomach. This was not supposed to happen! He was supposed to return to see me with a great response to treatment.

The next month, after completing emergency radiation therapy, Charlie came back to see me and I was greeted by the same hopeful eyes: Charlie’s, his wife’s, and their children’s. I held out my hand; his handshake was as firm as the first time. He seemed to relish the fact that he was able to literally crush my hand.

“So, what’s next?” he asked.

I was amazed that this person still had any kind of trust in me. Did he not realize that the treatment I prescribed a couple of months ago had completely failed to work for him? Did he realize he’d almost been paralyzed due to disease progression? It’s true that there is no guarantee that any given medicine will work for myeloma, but still….

We talked options again. I told him that we should try more standard chemotherapy regimens and then a stem cell transplant. He listened carefully, and nodded in agreement. We talked about my son again, and then he left to start treatment at home.

Charlie’s next year was not pleasant. Two different types of chemotherapy regimens failed to work. His bone marrow was packed with myeloma, and a heroic attempt to harvest his stem cells failed. This was November 2001, and all we had after 2 years was myeloma refractory to everything we tried and no real options on the table.

Each time they returned, I was constantly jolted by the love and affection of this family. As always, Charlie was full of hope and joy. He was imperturbable.

Rebounding From Failure

I am no stranger to failure. I’d desperately wanted to be a doctor, but for 2 years every medical school in India that I applied to had turned me down. I finally got accepted into medical school after 3 years.

Failing to get into medical school is a setback; failing to respond to myeloma is not the type of failure I could have possibly rebounded from. And here was Charlie, happy and peaceful amidst the worst possible situation.

There was one faint ray of hope. We were just opening a trial of PS-341, a new drug that had shown promise in two patients with myeloma. It was from a new drug class, one that had not been tested in humans before, called proteasome inhibitors. In simple terms, it wrecks the garbage disposal system of the cell, leading to accumulation of unwanted proteins and eventually tumor cell death.

I hesitantly brought this option forward to Charlie. I was nervous, considering what had happened in the thalidomide trial. By now, I should have known not to worry. Charlie was thrilled with the idea.

“Let’s do it,” he said,, and crushed my hand one more time.

What followed was nothing short of a miracle. He responded dramatically to the new drug. Although the median duration of response in this trial and many others subsequently was only a few months, Charlie had a sustained response as long as he stayed on the therapy.

Months passed, years passed, and he continued to respond. PS-341 was the blockbuster drug for myeloma that was eventually named bortezomib (Velcade). The trial was over, but Charlie’s response was not. We were able to switch him to a commercial drug.

Over the next 10 years, I saw Charlie and his family many times. He always chuckled with every firm handshake. He never met my kids in person, but he watched them grow by looking at pictures on my computer and then on my phone. He never met my wife, but he always asked about her.

By 2012, however, we slowly started to lose the battle. In the last year of his life, I watched Charlie slowly lose weight and lose color but never hope. A month before he died, he stopped by to thank me and asked his son to take a picture of the two of us, which I cherish. His death saddened me, but it gave me an opportunity to reflect on the things I learned from him.

The Lesson of True Imperturbability

Charlie taught me a lot about hope, trust, and determination. But most importantly, he taught me aequanimitas—true imperturbability, not just an external show of calm, but calmness and peace of mind internally. I’d read William Osler’s essay “Aequanimitas” as a medical student. Dr. Osler wanted physicians not only to appear to be imperturbable, but also to be truly in that frame of mind internally, without sacrificing empathy. This was a difficult concept to put into practice. As much as I was reminded of it, I always found myself being exactly the opposite.

Now, Charlie—and many other patients like him, despite all the challenges and realities of cancer—had showed me the path to equanimity.  ■

Dr. Rajkumar is Professor of Medicine and Chair of the Myeloma, Amyloidosis, Dysproteinemia Group at Mayo Clinic in Rochester, Minnesota.