September 6, 2018

Jason Harris

Andrew L. Pecora, MD, discusses the use of autologous stem cell transplantation in patients aged ≥75 years and the future of care in multiple myeloma.

Andrew L. Pecora, MD, editor in chief,John Theurer Cancer Center at Hackensack Meridian Health

There is no reason to avoid autologous stem cell transplantation (ASCT) in all patients with multiple myeloma who are older than 75 years, said Andrew L. Pecora, MD, president of Physician Services and chief innovation officer at Hackensack Meridian Health.

Patients with comorbidities, such as unstable diabetes or renal insufficiency, should not undergo ASCT, he explained. However, primary data suggest that transplantation can be safe and effective in an elderly population.

Pecora presented findings at the 2018 ASCO Annual Meeting from a study of 604 patients with multiple myeloma who received ASCT at the John Theurer Cancer Center. Forty-four patients were aged 75 to 84 years, while 560 were younger than 75 at the time of transplantation.

Results showed that the 3-year overall survival (OS) rate was 83.7% in the older cohort and 82.0% among younger patients. The median OS was 93.3 months and 127.8 months for the older and younger groups, respectively.

The 3-year progression-free survival (PFS) rate was 51.7% in the older group compared with 46.0% among younger patients. The median PFS was 36.1 months versus 33.7 months, respectively.

Moreover, older patients were able to tolerate high-dose melphalan conditioning.

“We'll need to do a larger prospective trial to prove it, but our data strongly suggest that you can safely apply ASCT in an appropriate 75-year-old or older patient, meaning that they have the right performance status, no comorbidities, and proper vital organ function,” Pecora said. “With those caveats being addressed, you can offer this potentially lifesaving therapy to an older patient.”

OncLive: Can you provide some background on your presentation?

In an interview with OncLive, Pecora, who is also the chief innovation officer and vice president of Cancer Services at the John Theurer Cancer Center at Hackensack University Medical Center, discussed the use of ASCT in patients aged ≥75 years and the future of care in multiple myeloma.Pecora: ASCT has been proven in multiple phase III, prospective, randomized trials to improve survival among patients with multiple myeloma, whether it was done upfront after an induction regimen or done later at the time of progression. The real question was, “Were the data applicable to an older population?” Most of these trials were in a population younger than 65 years.

At John Theurer Cancer Center, where we have one of the largest myeloma transplant programs in the world, we're fortunate enough to have a database that allowed us to look at our patients at or older than 75 years and compare them with younger patients. What was really striking and important was that the data were nearly superimposable. The toxicities and the benefits were similar in the older age group versus the younger age group.

Are there any comorbidities an older patient can have and still undergo ASCT?

Do older patients typically want to undergo ASCT?

Will ASCT continue to be the standard of care in multiple myeloma?

In addition to tolerating the toxicity, the principle concern that people have is that these are older stem cells. Are they going to engraft? Are they going to restore immunity? Or are they kind of tired? The answer is, “No.” The hematopoietic and immunologic reconstitution is just as brisk, as long as you give an adequate dose, as in a younger person.If a patient has hypertension, diabetes, or a myocardial infarction but doesn't have residual damage to the heart, then transplantation would be acceptable. However, if patients have active comorbidities, such as unstable diabetes, low ejection fraction after a heart attack, a deficit after a stroke, or renal insufficiency as a result of lifelong hypertension, that would not be an appropriate population.Age, in and of itself, does not define what a patient feels. I know a lot of 90-year-old patients who think they're young—and some of them live to be 105. You have to look at the patient. You have to, obviously, be certain a patient is articulating what they want—the outcome that matters most to them. If the patient is a “young” 75—still playing tennis, still working full-time, you have all your cognitive faculties, and you don't feel any different than when you were 65—we have proven that age, at least in ASCT for multiple myeloma, should not be a limiting factor.Transplant has been the steadiest thing in myeloma treatment over the past 15 years. With the advent of all the new drugs, first-generation immunomodulatory agents, monoclonal antibodies, proteasome inhibitors, and more, transplant is still there. It has still been shown that there is nothing that can provide, at least today, the benefit that a transplant can in a properly assessed patient.

What are other updates related to transplant are you excited about?

That said, what is the future? There are new therapies coming down the pike, such as CD38-targeted chimeric antigen receptor (CAR) T cells. Maybe that will supplant transplant, but I don't know that we will be able to cure myeloma or get very deep remissions with the current medications we have without transplant. I don't know that in the future—even with CAR T cells or CAR natural killer cells with a CD38 construct—if they will be powerful enough to eradicate myeloma without the disease having been cytoreduced by ASCT. If I had to bet, I can't say 10 years, but 5 years from now we will still be doing transplants.We're still learning more and more about how haploidentical bone marrow transplant can be used. When I first learned immunology and learned that we were going to do half matches, I thought that was tantamount to homicide. I couldn't believe it. However, it really does work and it seems that it's equivalent to a matched unrelated donor. It's more ubiquitous because you don't need to find someone a match. You just need a family member who’s a half match. That's important.

The use of immunomodulators [is also interesting]. We now have follow-up data from a trial we presented in 2017 showing that you can use checkpoint inhibitors after transplant and they may improve outcomes. That is pretty exciting.

Dong N, McKiernan, Siegel DSD, et al. Autologous stem cell transplantation in multiple myeloma patients over age 75. J Clin Oncol. 2018;36(suppl; abstr 8025)