Multiple Myeloma

For many years, the fight against multiple myeloma unfolded like a siege—slow gains measured against painful losses.

Now, researchers like Rafat Abonour, MD, speak optimistically about what the future holds. “A lot of us are bold enough to say we can cure multiple myeloma with the treatment we provide,” said Abonour, who oversees the myeloma program at Indiana University Melvin and Bren Simon Comprehensive Cancer.

Since 2013, eight therapies have gained federal approval, including second-generation proteasome inhibitors and newer immune-based options like bispecific antigens. Those advances have provided oncologists with a deeper bench of options for patients whose disease requires second or third options. For some, care for managing myeloma resembles managing a chronic condition.

Yet researchers still tackle thorny problems.

Why do some patients with precursor conditions like smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS) eventually progress to full-blown cancer? Why does myeloma surge back–even if immunotherapy wipes it out? What genetic factors power hyper-aggressive disease?

At the IU Simon Comprehensive Cancer Center, we are striving to find those answers. Our physicians and researchers work at the cutting edge, using the latest advances in genomic sequencing, machine learning and drug discovery. They also lead clinical trials for the newest options in immunotherapy.

Our progress against multiple myeloma is also made possible by generous donors like you.

“Donors have helped us build a strong program,” Abonour said. “It’s given us opportunities to be bold. We can ask big questions. Sometimes, doing that means you won’t get funded through traditional sources.”

Philanthropy will allow the IU Simon Comprehensive Cancer Center to continue to recruit talented scientists. It will underwrite collaborations with the Brown Center for Immunotherapy, turning newly discovered targets into immunotherapies manufactured at IU. And it can fund trials offering new therapies through IU Health’s statewide network.

Together, we can reach the ambitious goal of curing myeloma. Here is a look at our progress and what supporters make possible.

Brian Walker, PhD
Daniel and Lori Efroymson Professor of Oncology

Two questions continue to gnaw at researchers. Even as we learn more about myeloma, we still don’t know why less than 1 percent of patients with precursor conditions ultimately develop cancer. And even as therapies improve, we don’t understand why many patients see their disease eventually roar back.

Next-generation sequencing, which allows us to analyze DNA better, will help us answer those questions.

Using samples from IU’s myeloma registry, Walker and his team are revealing the cancer’s slow-motion evolution. In a condition like MGUS, for example, there are fewer genetic mutations or abnormalities.

The lab found one gene that might play a leading role. It guards the cell’s genome, making sure copying unfolds without a hitch. But when absent, errors pile up, and some pieces of code get misplaced. In samples taken from patients at regular intervals, Walker has found their frequency ramps up, allowing myeloma to emerge and crowd out normal cells rapidly.

Much of this data is new, but in time, it could pave the way for biomarkers oncologists use to keep tabs on patients. By understanding the cellular mechanics at work, Walker hopes we could single out at-risk individuals.

The lab also sequences samples based on the treatment a patient receives. Studying genetic changes over time might help us understand why some therapies, like newer proteasome inhibitors, fail. “There’s no point in treating patients with an ineffective therapy,” Walker said. “They could move on to other options.”

Attaya Suvannasankha, MD
Associate Professor of Clinical Medicine

Over the past several years, immunotherapy has shown promise in treating myeloma. Yet those treatments aren’t always durable–and still pose the risk of harsh side effects.

One solution might be bispecific antigens, cells retrofitted to identify a target on the surface of a myeloma cell and draw immune cells to take them out.

This past year, Suvannasankha led a clinical trial for a drug called linvoseltamab, which was effective in 90.3 percent of patients. Aside from the results, the therapy was also noticeable for milder side effects—making it easier to administer to older patients.

The treatment is unique because the antigen binds “gently” to the target and T cells, decreasing the workload to destroy myeloma. It also keeps the immune system from overdrive, lowering the risk of a cytokine storm. And most importantly, 78 percent of patients whose earlier therapies had failed remained in remission after a year.

To Suvannasankha, it’s early evidence that you can create more tolerable therapies without sacrificing effectiveness. “In this very difficult-to-treat group, where remaining options are so limited, to say that remission may continue at one year at such a high rate is pretty phenomenal,” she said.

Travis Johnson, PhD
Agnes Beaudry Professorship in Myeloma Research

 The best way to imagine cell sequencing is to think of a TV.

When next-generation sequencing arrived almost a decade ago, it allowed researchers to see genetic changes in high definition. Now, the arrival of single-cell sequencing is something like 4K, allowing scientists to analyze the profiles of individual cells from an entire group.

Doing so allows researchers to isolate cells with markers of high-risk melanoma, but other insights are buried in an avalanche of data. And Travis Johnson, PhD, an assistant professor of bioinformatics, uses powerful tools like machine learning to find them.

Unlike some cancers, where one mutation drives the disease, myeloma relies on multiple changes playing out. “It’s multifaceted on a scale the human mind can’t comprehend,” Johnson said. “It’s a bad disease, and its complexity makes it a fascinating problem to work on.”

Using existing tools and algorithms, Johnson hunts for patterns in data from a small group of patients and compares it to other datasets available to researchers. That way, he sees if trends scale up. He can also add other variables–like risk profiles for certain patients—and see if others emerge.

Often, Johnson focuses on copying errors for genes linked with more aggressive forms of myeloma. He passes his findings along to Brian Walker, PhD, a professor of medical and molecular genetics, whose lab tries to validate them at the lab bench. For his part, Walker provides feedback that helps Johnson make tweaks.

Together, Johnson and Walker could discover genetic markers for high-risk myeloma or hint at a substantial likelihood of recurrence. Genomic testing would allow oncologists to identify and track patients most at risk. Patients can start treatment and halt myeloma’s return when they show the marker.

Charitable support is essential for researchers like Johnson, who are in the early stages of their careers. A generous estate gift from Jim Beaudry, PhD, lets Johnson carve out time to focus on myeloma projects and pay for a graduate student to assist with analysis. His data helps peers at IU and can pave the way for large grants from the NIH.

Maci Cox and Ke Yang

Most days, Maci Cox’s job as a social worker supporting myeloma patients is about stacking small gestures: handing out a business card, arranging transportation, lining up lodging, or helping someone navigate an insurer’s website.

“It’s solution-based,” Cox said. “When a patient has a problem, my brain just starts going.”

It’s also a helping hand made possible by Miles for Myeloma funding directed to enhancing patient care through the IU Health Foundation.

Along with Ke Yang, a nurse practitioner, Cox ensures patients receive care that treats the whole person and enhances their quality of life. They work out of an office tucked away on the second floor of the IU Melvin and Bren Simon Comprehensive Cancer Center just steps away from infusion rooms.

They meet with myeloma patients who have completed induction therapy and are preparing for a bone marrow transplant. Yang addresses any medical questions they might have about the procedure, its side effects, and outcomes. Meanwhile, Cox helps guide patients in the weeks and months afterward.

That includes administering a psychological assessment. During that meeting, Cox also learns where a patient is working, the status of their family, and what support system they might have. It helps her ascertain what’s needed to ensure the patient stays on track with follow-up care.

Often, a patient’s needs are practical. If they need lodging in Indianapolis, Cox can connect them with community foundations that offer it. For transportation she might be able to obtain a gas card from a social service agency.

“It sounds really simple,” said Cox, who sees up to 15 people each week, “but it’s just hearing patients and making sure they feel supported.”

Cox’s aspiration to work with cancer patients started as an intern with a support group while she earned a master’s degree at the University of Southern Indiana. So far, the reality has been everything she wanted.

“Everyone is just so grateful to be here–the staff in the clinic, the doctors, and the nurses,” she said. “The gratitude patients show confirms my decision to do this.”