A Myeloma Titan
Sagar Lonial’s Unfailing Quest
When all you want to do is be part of the fire
All you want to do is be the fire part of fire
~ Bill Callahan, Sycamore
The mightiest Greek gods may have ruled from Olympus, but their offspring connected them to humanity. The Muses, for example, presided over the very things that make humans human, including comedy, dance, poetry, music and history. Other progeny of the Gods gave humans skills and qualities, like Prometheus with fire and forethought, Asclepius with medicine and surgery, and Tyche with destiny and luck.
Myeloma, too, has its Olympus of sorts, as I have written in the past. Thankfully those ensconced there are not as distant, fickle or anything close to being potentially as venal as the ones in Greek mythology. They are fully human, their deeds born of effort and determination.
History tends to give inordinate amount of credit to those who were first in doing or discovering something. Rightly so. I do it in the articles I write. More often than not, however, it’s the ones who come after, who expand, open, or to use the vogue marketing term, add value, sometimes immense, to pioneers’ achievements.
Yet those following pathfinders, who build on their achievements deserve as much or more consideration. They absorbed the lessons from those who came before them; they often have a much wider perspective of what needs to be done to keep advancing.
To take one example, Wilber Wright may have invented the flying machine with his brother, but he didn’t live long enough to see the world from above the clouds. Nor could he likely grasp what it took to get there. His knowledge of aviation paled in comparison to that of a modern-day pilot.
The same analogy holds in medicine. Especially in rare diseases like myeloma. It seems the rarer they are, so too is their complexity.
Few myeloma experts today stand more firmly on the shoulders of giants than Sagar Lonial. Under his leadership in the past quarter century, Atlanta, Georgia’s Emory University Winship Cancer Institute has become a research and treatment Mecca for hematology, oncology, and especially myeloma.
In spite of progress made and plaudits received, Lonial still has the feeling of just getting started, “we have to think about things differently. This idea: first you do induction, and then you do consolidation, and then you do maintenance,” summing up the prevailing treatment paradigm, needs to be reevaluated, “I don’t know that that’s the right way to think about it.” As he looks to the future, he finds inspiration in the past.
“We have five or six new immune targets, we have to figure out how to put them together in a logical way,” he continued, “and I think we have to go back to the lessons we’ve learned from Bart Barlogie. Why not put the best drugs we have together, all at one time over the course of two years? Let’s hit it hard, get people into deep responses and see whether we’re done.” Expectations have changed dramatically.
“There’s no question in my mind that we have the tools now. It's just a matter of having the discipline to break paradigms from where we were 10 years ago.” Yet Lonial’s sense of urgency is tempered, knowing “if we can't take it beyond that with the tools we have now, then all we will have done is support Phase III clinical trials that are incremental.”
“The Bart influence” is strong. Like Barlogie, Lonial has a visionary’s confidence: “I want big changes that can cure patients.” His self-assurance might seem like false bravado when considering the circumstances of his arrival at Emory in 2000.
Just a couple of years earlier, as Lonial was nearing completion of his medical internship and residency at Houston’s Baylor College of Medicine, he was deciding where to go for his hematology fellowship, “I was looking at either MD Anderson or Emory.”
Emory was appealing because he had worked with faculty now there who were all in Baltimore during his undergraduate biology studies at Johns Hopkins Hopkins University. He decided to go “there to train and become a leukemia and transplant doctor.” It seemed a perfect fit.
During his residency at Baylor, “everybody knew heme malignancy was what I wanted when I was an intern. I wanted to do that and transplant.” It was so well-known, it became something of a friendly joke. “Somebody would come in with a case in the morning of, for example, community-acquired pneumonia and the chief resident would look at me and ask, ‘do you want to transplant that guy?’ They knew what my interest was.”
Lonial’s arrival at Emory, however, was less than promising. When he got there, all but one of his former Hopkins colleagues/faculty had left for other places, “basically the department was decimated. So, I got there, started my fellowship” and was pretty much alone, thinking about “turning around and going back to Houston, to be honest.” Instead, he got to work. Leukemia was his specialty of choice, with no thoughts of myeloma.
“I starting to write protocols and was just getting frustrated, I couldn’t get the stuff going like I wanted them to go,” he recalled, “but sometimes a vacuum is an opportunity.”
He was assigned to organize a professional education meeting, inviting prominent experts in differing hematological specialties from around the U.S. to speak. One was Dana-Farber’s Kenneth Anderson. Apparently, Lonial made an impression on Anderson. They would meet again in December 2001 at the annual American Society of Hematology (ASH) meeting in Orlando, Florida.
Anderson must obviously have been impressed with Lonial after they met at Emory. Like an experienced fly fisherman, Anderson was probably thinking of what kind of bait he could hook Lonial with the next time they met.
“I was walking out of a café at ASH,” recalled Lonial, “and I turned left instead of right to go to a session and ran into Ken Anderson.” It’s not crazy to speculate that, like a fly fisherman in rubber overalls standing patiently in a cold river, waiting to bag a trophy salmon, Anderson’s chance encounter wasn’t random luck. He asked, “where are you headed?” Lonial replied, “I’m going to this leukemia session.” To which Anderson replied, “forget that, follow me.”
Once he had Lonial in his sights, Anderson wasn’t going to let him escape. He yanked the hook to make sure he had Lonial firmly on the line. Anderson confidently started reeling him in, “I’m going to take you to see some myeloma docs in the APEX investigator meeting.”
As Lonial remembers it, Anderson said, “We’re going to set your lab up, get you access to trials, and we’re going to make you a myeloma center.”
Imagine starting out the night thinking you’re going to see a concert by Lifehouse, a long-forgotten band with a longer-forgotten song that topped the 2001 charts, and instead, getting a backstage pass to a Rolling Stones concert and being asked to join the tour as one of their top roadies. It might give you a sense of what Lonial was about to experience.
APEX wasn’t some run-of-the-mill clinical trial. Assessment of Proteasome inhibition for Extending Remissions confirmed the unprecedented efficacy of the proteasome inhibitor that Robert Orlowski first confirmed was effective in myeloma, known at various stages as PS-341, bortezomib and Velcade. Led by primary investigator Paul Richardson, Anderson’s colleague at Dana-Farber, APEX “was an international, prospective, randomized, Phase III study conducted at 95 centers worldwide [that] took only 14 months to complete.” Lonial was the youngest of an international “Who’s Who” of 21 myeloma researchers representing nine nations.
The trial was key in gaining FDA approval for Velcade in relapsed/refractory disease in 2003. An extended follow-up study led to approval for front-line treatment in 2007.
Lonial’s “first big paper was taking APEX and SUMMIT [the first large clinical trial led by Barlogie that confirmed bortezomib’s therapeutic benefit] data for Velcade and explaining its risk of thrombocytopenia [low numbers of platelets in blood]. We went back and charted all the patients that got Velcade on a spreadsheet and went through the data” and found “community docs were not giving the Velcade when the platelets dropped, like they would with chemo.”
But “this was not the same,” leading Lonial to partner with one of his PhDs to ask, “what happens when you give Velcade to a mouse? Can it be shown that the platelets (megakaryocytes) don't go away like they do with chemo? So, we did that study and showed the same thing happened in mice that happened in people. You don’t need to hold the drug.”
In another instance of how quickly advances are being made in myeloma, Lonial said, “It's old, probably not as relevant now as it was back then. But it was really our first translational contribution to the field. We went from a bedside observation, and it took to the bench. That was sort of cool for us to do.”
Later, Lonial was the primary investigator for “the first three big antibodies in myeloma – elotuzumab, daratumumab, belantamab mafodotin – we were there.”
Back at Emory, this research activity, according to Lonial, “really got us more and more on the horizon.” In early years, his staff “saw between 50 to 75 myeloma patients a year. This year we'll see more than 4,500. I added a half-day clinic as just to see myeloma clinical trials patients.”
The growing staff, steadily increasing numbers of patients, and the experience with bortezomib (Velcade) opened doors to participate in other key clinical trials of now common myeloma treatments. “We did lenalidomide, we did pomalidomide, carfilzomib, all that stuff, all because of that chance meeting with Ken Anderson,” said Lonial, “I mean, I was fortunate early on, even back in 2001.”
Emory administrators, much like Anderson when he first met Lonial, quickly picked up on what they had. “In subsequent years I had leaders at the top who basically said, ‘you tell us what you want to do and we're going to clear the barriers for you to be successful.’ And that made my life a lot easier. I was able to make the case that this is really important,” Lonial gratefully recalled.
“Our whole commitment all along was to build a translational program that provided access to new therapies that nobody else around us had. The advantage that Emory has is we're pretty much the only academic center in the state.”
Patients from throughout Georgia and neighboring states went to Emory because it had “access to new drugs,” and more importantly, “we wanted to make sure that we had a team that was prepared to take care of them. We had advance practice providers (APPs) dedicated to myeloma even back then.” Emory’s transplant program – although we don’t do allogeneic transplants anymore, but certainly auto transplants ourselves – grew as well.
“We were on the ground floor of what would become a huge revolution” and staying close to patients was paramount. “We gave our cell phone numbers out to everybody; people knew how to get a hold of us. We communicated back with referring docs and built our network. Everything sort of fell into place to support the growth of the team.”
Ajay Nooka, who now leads the myeloma program and serves as Winship’s Associate Director of Clinical Research, once noted “only about half to a quarter of those patients participating in Emory clinical trials are actually treated” there, the rest being treated by community physicians” with whom they work very closely. “They know us, we do a lot of outreach in the community, and in an area that's as big as Georgia and the surrounding states, that can go a long way.”
Emory’s reputation helped it to “start growing organically and were really committed to a sort of one-stop-shopping,” explained Lonial further, “in a lot of places, a patient goes to one doctor who advises you what to do for myeloma, but if you need a transplant, you got to see somebody else. We wanted myeloma docs to decide what's the best treatment throughout the course of a patient's journey, with our transplant team on board. So, we're not sending them to see different people to get different opinions.”
Another lesson, “which, actually, I'll say I sort of learned from Bart Barlogie is: we all said very early on we're all going to do the same thing. We’ll argue and fight over what we think is right internally, but once we decide, we are all on board. That allows us to have a level of consistency and retrospective access to data that most other programs don't have.”
This practice differs from many other clinics around the nation, where “what you're going to be recommended” for treatment “depends on who you see. We did not want that.” And Emory was, “in the beginning, small enough that our power was in consistency and in data.” Now, the Emory database, built by Nooka, “has more than 5,000 patients, which allows us to do long follow up. We know exactly what happens to people over time.”
Under Lonial’s leadership, the Emory staff has become a myeloma “Who’s Who” of its own.
“Jonathan Kaufman was really the first to join the group.” He is now a lead investigator in the use of the novel agents venetoclax and tocilizumab in myeloma. Nooka came on board after him. “Larry Boise was our first real scientist” who focused on cell and molecular biology.
“When Madhav Dhodapkar got here [from Yale, prior to that working in Arkansas with Barlogie], probably five years ago, we started adding in samples and the research piece to get even stronger than before.”
Craig Hofmeister, joined Lonial’s team in 2018, coming from Ohio State’s James Cancer Center. Now a full professor, Hofmeister is known as being a clear communicator and is a sought-after speaker for patient education events.
Nisha Joseph, who came to Emory after earning her MD at Ohio State for residencies in internal medicine and hematology/oncology was promoted to the staff in 2018. Her mother, Gita Joseph, is a hematologist/oncologist at Louisville, Kentucky’s Baptist Health who also treats myeloma patients. Joseph and Lonial are both natives of Louisville.
Not only was Lonial born and raised in Louisville, it was where, on his first day at the University of Louisville School of Medicine, he met his future wife, Jennifer Culley, also a Kentucky native. “We were paired as lab partners.” She is currently Medical Director for the Medical Optimization Clinic at Emory’s Department of Orthopaedics & Spine Center after retiring from Atlanta’s VA Medical Center.
Being closer to home was a big reason Lonial chose Emory over MD Anderson for his hematology fellowship. “My family was still in Kentucky; my wife's family is in Kentucky. Atlanta is a lot closer than Houston.” If they didn’t fly, a 6 ½ drive was more doable than a 14 ½ hour one. Especially with their then young children, Hallie and Ben, in tow.
“My dad came to the U.S. from India for college. He was an engineer who moved to Louisville to work for General Electric. Later he got his PhD in marketing and he taught at the university’s business school for close to 40 years. He was an amazing teacher, but tough. So, I guess I’m first generation. Grew up in sort of a traditional immigrant household. Worked hard. Loved school.”
Medicine wasn’t an obvious direction in life. “There aren't any physicians in our family, really,” the closest connection was his mother, a nutritionist. In elementary school, he “loved science, and then in high school, I loved biology.” He “was also a bit of a debater. “For me, the tension was sort of medicine versus law.”
Medicine won out. As he remembers it, “I think it was my sophomore year. RAS was the ‘oncogene of the year’ or something like that in a Time magazine article. And I remember writing a term paper on that and realizing that's what I want to do.” Any thoughts of law took a seat way in the back. “I wanted to take care of cancer patients, thinking, ‘this is going to be really cool.’”
After high school, it was on to Hopkins. In his first week, he “signed up to work in the adult leukemia lab” and continued to work there until graduation four years later. “I was there during the summers. I was there during the week. Just loved it.” In addition to the work assigned to him, he “had two of [his] own projects,” becoming enamored with translational research. “Sometimes I would actually go on rounds with the leukemia docs at Hopkins just to see the other side of what I was doing.”
Thankfully, considering where life took him, leukemia joined potential law studies in the back row in favor of myeloma.
On the other hand, for anyone who has experienced Lonial speaking to professional audiences, in examination rooms, or at patient education events, it becomes immediately apparent that he would have made one heck of an attorney arguing a case in court. He speaks with a confident authority and a grasp of facts with a precision that few, if any, of his colleagues can match. He hasn’t lost any of the debating skills he honed in high school. He’s only gotten better.
Today he is the Chief Medical Officer of Emory’s Winship Cancer Institute, a named professor (the Anne and Bernard Gray Family Chair in Cancer) at Emory’s School of Medicine, and its Professor and Chair of the Department of Hematology and Medical Oncology. He’s come a long way since making that wrong turn in Orlando.
Roman mythology’s counterpart to Tycho is Fortuna. It would be easy to conclude that Lonial had a way of keeping Fortuna busy; she usually makes her wishes known with subtlety. Perhaps she pointed out an article in a magazine at an impressionable time, maybe she influenced lab partner matching on the first day of medical school, she might even have made him take a wrong turn at the right time.
On the other hand, as Chi Chi Rodriguez, the colorful golf pro once said, “No one has much luck around the greens as one who practices a lot.” Lonial obviously likes to practice, it pays off in his work, life, and hopefully, in his golf game.
The Olympians of myeloma knew that. Robert Kyle, Jean-Luc Harousseau, Kenneth Anderson, and Jesús San Miguel all wrote letters in support of the promotions Lonial has earned at Emory.
Although he’s never seen them, Lonial said, “they’ve told me what was in them, and they’re just so kind and welcoming. It made a huge difference. A huge difference.”
Sagar Lonial is one of a handful of next generation trailblazers with quite a different view of the myeloma landscape than his forebears. Under his vision and leadership, Emory University’s Winship Cancer Institute has blossomed into one of the world’s leading research and treatment centers in hematology, oncology, and especially myeloma.
Although he’d deny it, he’s made a huge difference.
Photos courtesy of Sagar Lonial.
Lovely piece, Greg! Keep ‘em coming.