Thomas G. Martin, MD
Autologous stem cell transplantation (ASCT) continues to have an imperative role in the multiple myeloma paradigm, as most patients with the disease are able to tolerate it and it is a go-to strategy for physicians, explained Thomas G. Martin, MD.
The best sequence of treatment for newly diagnosed patients, he added, is induction therapy, between 3 and 6 cycles of triplet-based therapy, followed by ASCT. However, with all of the available therapies in the myeloma landscape, the challenge lies in figuring out which patients derive the most benefit from which agents, Martin said.
Other therapeutic developments continue to show encouraging activity as monotherapy and combination regimens in the landscape, such as proteasome inhibitors, monoclonal antibodies, immunomodulatory agents, and potentially, chimeric antigen receptor (CAR) T-cell therapy.
“The future of myeloma is very bright,” said Martin. “It's really fun to be a myeloma doctor with all of these therapies we have. It is only going to get better, especially with CAR T-cell therapy. Off-the-shelf products will also have an impact.”
In an interview during the 2018 OncLive®
State of the Science Summit™ on Hematologic Malignancies, Martin, associate director of the Myeloma Program at the University of California, San Francisco, discussed the clinical utility of ASCT and the rapidly evolving treatment paradigm of myeloma.
OncLive: Please provide an overview of your presentation.
: There are some limitations to ASCT. Patients older than age 75 are rarely transplant candidates. I would say almost all patients younger than 70 are eligible candidates. Most of the patients, if they're ineligible, it's because they have ongoing pulmonary comorbidities or cardiac issues.
In general, most patients can tolerate transplant. We have done a number of randomized trials in the frontline setting—at least 4—where patients are randomized to either upfront single ASCT versus standard triplet therapy. Essentially, in every one of the trials, we see that the PFS in the depth of remission is better if you undergo ASCT. Many of those trials have looked at delayed transplant or salvage transplant. This is when disease recurs.
Unfortunately, when people have relapsed disease, most of the time they don't receive ASCT. We don't have a lot of data in the novel era suggesting that's a better strategy. For me, I stick with frontline transplant.
I also spoke about maintenance-based therapy. The data these days really support this following transplant. We have had a number of randomized trials looking at single-agent lenalidomide (Revlimid) as maintenance. In a meta-analysis, patients who received lenalidomide had a 2.5-year advantage in terms of overall survival compared with patients who received placebo. Lenalidomide is now the standard of care for posttransplant patients.
The one thing that comes into question is what to do with patients who have high-risk disease, in terms of transplant and maintenance. In the United States, we did a trial looking at a single ASCT versus tandem ASCT. There was no difference in terms of benefit. That was the StaMINA trial. There was also a European trial called the EMN02 trial, which looked at bortezomib-based induction with cyclophosphamide and dexamethasone. Those patients who received induction followed by tandem ASCT did better than those who received induction followed by single transplant. The best results were seen in patients with high-risk disease.
The difference between these studies is that in the European study, they didn't use an immunomodulatory agent as initial induction therapy. In the United States, almost every patient gets immunotherapy and a proteasome inhibitor. That is why, in the United States, if you still give that regimen, a single transplant is probably best. In terms of maintenance, there was a trial done in the United Kingdom that showed benefit with lenalidomide maintenance, even if you had high-risk disease.
The future is bright in terms of all the agents we have. In the future, because we're seeing such great activity in patients who are receiving CAR T-cell therapy, it's very possible this type of treatment early on will limit the use of transplant. We will need a randomized trial looking at this.
In terms of induction, is lenalidomide, bortezomib, and dexamethasone (RVd) still the standard or can physicians use carfilzomib (Kyprolis), lenalidomide, and dexamethasone (KRd)?
We have had several trials that have combined a proteasome inhibitor plus an immunomodulatory agent versus a proteasome inhibitor plus an alkylating agent. We have done that with bortezomib and carfilzomib. In all these randomized trials, the arms that had a proteasome inhibitor plus an immunotherapy did better. Frontline therapy should be a proteasome inhibitor, immunotherapy, and dexamethasone. This is in a transplant-ineligible population.