20 Years of Advancements Brings a 'Luxury' of Treatment Options for Patients With Myeloma

Advancements in the treatment of multiple myeloma over the past 20 years have significantly affected the lives of thousands upon thousand of patients.

“The survival of (patients with myeloma) has more than quadrupled over the past 20 years, and we’ve come from conventional chemotherapies to targeted novel therapies,” said Dr. Saad Z. Usmani, hematologic oncologist and chief of myeloma service at Memorial Sloan Kettering Cancer Center in New York City, in an interview with CURE®.

Treatment Advancements

When Usmani was a trainee, there were only two classes of drugs for patients with multiple myeloma in their first line of treatment: immunomodulatory drugs (IMIDs) such as Thalomid (thalidomide) and Revlimid (lenalidomide) and the proteasome inhibitor (PI) Velcade (bortezomib). Then came the next-generation immunomodulatory drug Pomalyst (pomalidomide) and second-generation proteasome inhibitors Kyprolis (carfilzomib) and Ninlaro (ixazomib).

The real revolution started in 2010, when there was a bigger focus on immune-based treatment approaches such as targeting specific surface antigens, chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies.

“All of those therapies just really propelled and started to change the landscape of myeloma treatment,” he said.

Usmani added that conversations among doctors also started changing over the years, and they realized that combining drugs could lead to better survival outcomes. As a result, combination therapies began penetrating the space around 2015 and 2016, he noted. And now the standard of care in the second-line treatment of patients with relapsed multiple myeloma is three-drug combinations known as triplets.

“I think we have better tolerability for these therapies in myeloma compared to the conventional chemotherapies. We have better responses (and) better survival outcomes,” he explained. “We have learned to (treat) patients more effectively over time, manage side effects better with dose adjustments and alternate schedules, and because of these advances we also have a lot of ... younger hematologist oncologist trainees who have shown interest in doing quality research in this disease. (There) has been an influx of good, fresh ideas, as well, over time.”

Dr. Gurbakhash Kaur, an assistant professor of internal medicine at UT Southwestern Medical Center in Dallas, has been specializing in multiple myeloma for three years. Although she was not “in the trenches treating patients" at that time Usmani was, she agrees that the advancements for treating multiple myeloma have been significant over the years.

She also noted that 20 years ago, IMID- and PI-based therapies were not even approved for multiple myeloma. Since then there have been over 16 drug approvals for multiple myeloma. which researchers reported at the 2021 American Society of Hematology Annual Meeting and Exposition.

“The type of therapy you choose for second line takes into account patients’ comorbidities, preferences and quality of life. Treatment at any stage of relapse of myeloma is important, and you have to make the most informed decision and the right decision for the patient,” she explained.

Kaur mentioned the increaseduse of the combination of CD38 antibodies like Darzalex (daratumumab) and Sarclisa (isatuximab), CD38 antibodies and second- generation PIs such as Kyprolis and Ninlaro with newer immunomodulatory agents like Pomalyst are used mostly in the second line.

Quality-of-Life Advancements

Usmani and Kaur have seen significant improvements in quality of life, something they both said is important for their patients.

“The patients are at the center of (it) ... they are the central keys to everything that we do,” Usmani said. “When I meet with patients, I tell them ... the patient is the most important person in the room. These advancements and all these new data are helping us manage our patients better, take care of them better, give them the opportunity to have a better quality of life, to do things that really matter (and) to spend time with their loved ones.”

He added that over the years, doctors have come to understand that myeloma is typically a disease of older age. Treatments today are better tolerated for older patients than past conventional chemotherapies. The safety and side effect profiles are also better, which translates to a better quality of life.

For example, infusing Darzalex used to take eight hours, and Kaur would dread having to tell a patient they would have to go through that. Over the years the process has been dramatically shortened, and now administration is a shot under the skin and takes only five minutes.

“That itself has changed patient’s experience and quality of life, and I don’t even blink when I have to introduce (Darzalex) to a patient anymore,” Kaur noted.

She said that physicians now have a “luxury” of options that were not available before, meaning that if a patient does not want to receive an intravenous infusion, there may be an oral option instead. For patients in treatment, a main focus is on toxicities and quality of life, which explains how far management of the disease has come in 20 years.

“To me, that’s the most amazing thing about the advancements we’ve made, that we as myeloma physicians ... are starting to address the quality-of-life questions a lot more than before,” Kaur said.

The Next 20 Years

Usmani and Kaur agree that immunotherapies, such as bispecific antibodies, and CAR-T cell therapies are the future for managing multiple myeloma. Currently, these therapies target a surface marker on myeloma cells called B-cell maturation antigen, or BCMA, but other surface targets are on the horizon.

Usmani added that new cell modifications and biomarker-driven treatments, such as Venclexta (venetoclax), will become important players in the second-line treatment of relapsed disease. He said important metrics in these new treatments include whether they are safe for the patients, are effective in a deeper response or lead to better progression-free survival (or the time during and after treatment when the patient lives without disease progression).

Kaur added that the ultimate goal is to have a treatment that is curative, and with these new immunotherapies doctors might be able to get there. She is hopeful for the future of patients with multiple myeloma, but she said there is more work to do in understanding how to sequence new treatments.

“I do have quite a bit of hope of these newer agents moving further up front. ... Myeloma, there is a science to it, an art to it, which is the personalized aspect of it. ... What we need to figure out (is) how to sequence these medications and have a more scientific approach. ... What are the right combinations? We’re still figuring out those (answers), but that’s my hope for the future,” Kaur concluded.

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