Is Early Immunotherapy a Game Changer?

Sagar Lonial, MD, is an internationally recognized leader in multiple myeloma research who has led landmark studies on the genetic diversity of the disease, participated in practice-changing trials, and spearheaded real-world data collection. But his focus on myeloma happened mostly by chance.

In 2001, Lonial was a junior faculty member at Winship Cancer Institute of Emory University, in Atlanta. He was becoming increasingly frustrated with a lack of advances in his area of focus — leukemia and allogeneic transplant — when he bumped into Ken Anderson, MD, in the hallway at the American Society of Hematology (ASH) annual meeting.

“I just happened to run into Ken Anderson at ASH, who said, ‘Where are you going?’ I said, ‘I’m going to a leukemia session,’ and he said, ‘Why? Come follow me,’” recalls Lonial, who currently serves as the chief medical officer at Winship Cancer Institute and chair of the Department of Hematology and Medical Oncology at Emory University School of Medicine.

Anderson, who was already a leader in the myeloma field, brought him to an investigator’s meeting about bortezomib, a novel agent for myeloma. That chance encounter, and the collaboration and mentorship from Anderson that followed, helped Lonial build Emory’s myeloma program into an internationally recognized leader in the field.

“I met Sagar over 25 years ago and at that time recognized what a rising star he was and encouraged him to pursue studies and clinical trials in multiple myeloma,” said Anderson, director of the LeBow Institute for Myeloma Therapeutics and Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in Boston.

“This is now 25 years later, and Sagar has succeeded beyond belief. He’s grown the multiple myeloma center at Emory Winship Cancer Institute into a world-class, leading research and clinical care center of excellence in the world.”

The experience of changing his research focus from leukemia to myeloma is why Lonial advises junior faculty to avoid narrowing their focus for the first few years in academia.

“Don’t say no to anything the first 4 years because you never know what opportunity is going to take you to where you are today,” Lonial said. “Being open to change, being open to new ideas, doing something you never thought you’d be able to do, that challenge is what keeps you fresh.”

Following the Science

From the start, Lonial has been following the science. He was in high school when the identification of the RAS oncogene and its potential in cancer therapeutics inspired him to become an oncologist. He started working in the leukemia lab at Johns Hopkins during his freshman year as an undergraduate and was soon helping to design experiments on the newly cloned granulocyte- and granulocyte-macrophage colony-stimulating factor.

In that lab, he met one of his first mentors, Judy Karp, MD, now his friend and collaborator for 30 years. “Her commitment to the science and clinical trials is probably what got me started,” Lonial said.

Lonial returned home to Kentucky to attend the University of Louisville School of Medicine, where he met his future wife — his assigned lab partner — on the first day of medical school. Already then, he had an interest in translational research and started working with an oncologist at Louisville on research projects.

Lonial went on to residency at Baylor College of Medicine in Houston, where he worked closely with the transplant specialist, Phil McCarthy, MD, who is now at Roswell Park in Buffalo, New York.

When it came time to start his fellowship, Lonial chose Emory, in part for the chance to work with some faculty members he had known from his time at Johns Hopkins who had moved to Emory. But by the time he arrived in Atlanta, that group had left. There was big faculty turnover then, and the department was in disarray. Nevertheless, Lonial said it ended up being an opportunity for him.

“There weren’t a lot of people blocking me to do what I wanted to do,” he said. “If you have good ideas and you have good external support, things just sort of fell into place, and I was able to write a couple of protocols and do some things as a fellow that I don’t think I would have been able to do [otherwise].”

After switching his focus to myeloma research, Lonial quickly made his mark on the evolving field. He has conducted laboratory work evaluating the impact of purified dendritic cell subsets on immune responses against antigens and has conducted several trials assessing the role of cytokines on dendritic cell content and immune recovery after transplant. Over the years, he’s led trials for multiple novel agents that have gone on to become standard of care in myeloma, from immunomodulatory drugs (IMiDs) and proteasome inhibitors to monoclonal antibodies. More recently, he has investigated the synergistic inhibition of the PI3K/Akt pathway and the role of 14-3-3 in proteasome function.

In June 2025, Lonial received the Robert A. Kyle Lifetime Achievement Award from the International Myeloma Foundation for his significant contributions in the field of myeloma research.

Evolving the Myeloma Field

Over the past 25 years, Lonial has had a front-row seat on advances in the myeloma treatment landscape.

“Back then, it was melphalan and thalidomide. That’s pretty much all we had,” Lonial said.

Early on, Lonial said that he and his colleagues at Emory were “big believers” in maximizing early responses by consolidating with a transplant and using maintenance therapy to keep patients under control. But the emergence of monoclonal antibodies, proteasome inhibitors, and second-generation IMiDs allowed them to change the treatment paradigm and begin to achieve complete remissions.

Lonial recalls that Emory was ahead of the curve on the concept of using combination therapy in myeloma, rolling it out before phase 3 trials results made it standard of care. That allowed them to build a real-world dataset of patient outcomes showing that the approach worked and to achieve “unprecedented durations of remission,” Lonial said.

“As we develop new molecules, we further refine the model, highlighting the idea of combining therapies as ultimately the best way to kill myeloma,” he said.

Next, Lonial said he’s excited to move that concept forward with immunotherapies. He is currently working with colleagues on designing a trial to assess a concept called “total immune therapy” that would give patients with newly diagnosed myeloma treatment for every immune target within the first 2 years of treatment and then stop therapy, with the idea being to never let myeloma develop resistance. “This idea of sort of cycling through and trying to really eliminate every subclone is what we’re proposing for the next trial from us,” Lonial said.

Rowing in the Same Direction

Lonial splits his time among his research, administrative, and clinical responsibilities, but he sees teamwork as important to making all those roles work.

Lonial is in the clinic once a week, so he relies on a team of advanced practice providers to be the “eyes and ears” of the program and manage patients throughout the week. He takes a similar approach to managing the clinical trial load. The team of eight myeloma specialists divide the 25-30 open trials among themselves, but they generally enroll patients to all of them. “We really want to make sure that we are pulling oars in the same direction,” Lonial said.

Lonial tends to lead the early-phase trials of new drugs, giving junior faculty more opportunities to step up on the management of phase 2 and 3 trials, he said.

He also works with the myeloma clinicians on having a unified practice approach. This type of team approach allowed the group to develop large, real-world datasets comparing RVD (lenalidomide, bortezomib, dexamethasone) with dara-RVD (daratumumab + RVD) in clinical practice.

This unified practice approach, spearheaded by Lonial, has had a significant impact on the treatment of patients with myeloma, said Larry Boise, PhD, a professor of hematology and medical oncology at Emory, who has worked with Lonial for the past 16 years.

“He is all about team,” Boise said. “Even though he’s obviously highly accomplished at what he does, and has been recognized for that, he is very clear that he believes that his success has been because of the culture and environment here at Emory in the myeloma program. What he won’t say is that he’s the one who created it. He’s the one who created that culture, and everyone has bought in because everyone gets their fair share of credit. He takes very little.”

Challenges in Oncology

Lonial sees his connection with patients as the most fulfilling part of his job, but he recognizes that it gets harder for physicians to build those relationships while also needing to fulfill requirements related to electronic medical records and patient volume. “That’s the real challenge that I see in medicine today,” he said.

The other challenge for the field is creating greater access for patients to the full spectrum of advances in oncology.

“We have all these great new drugs — CAR [chimeric antigen receptor] T cells and bispecifics — they are going to be in more than hematologic malignancies; they are going to be in solid tumors. But the ability for patients in underserved areas to get them is a real challenge,” Lonial said. “Figuring out how we make that access a little bit more democratic, I think, is going to ultimately be the social challenge that we as oncologists need to help deliver.”

Lonial disclosed having ties with AbbVie, Amgen, BMS, Genentech, GSK, Janssen, Novartis, Pfizer, Regeneron, Takeda, and TG Therapeutics.