S. Vincent Rajkumar, MD
In the last decade, multiple myeloma has seen a change in diagnostic criteria, an updated staging system, new response criteria, and several novel therapeutic options, explained S. Vincent Rajkumar, MD.
“Newly diagnosed multiple myeloma is a challenge, and relapsed disease is a bigger challenge because there are so many more trials and so many more regimens,” said Rajkumar, a professor of medicine at the Mayo Clinic, during his presentation at the 15th
International Conference on Malignant Lymphoma. “We are going to have many more complex problems in the future. Many [investigational drugs] are in phase III trials and many of them will get approved for multiple myeloma. We have several different options coming up, which will eventually impact the management of relapsed and maybe even newly diagnosed patients.”
New treatment options include an expanded use of quadruplet regimens, including, most recently, the combination of daratumumab (Darzalex) plus bortezomib (Velcade)/thalidomide/dexamethasone (DVTd), which has been evaluated in the phase III CASSIOPEIA (MMY3006) study.
In the trial, demonstrated improved depth of response in patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant. The stringent complete response rate at day 100 post-ASCT was 28.9% in patients who received the daratumumab regimen compared with 20.3% in those who received VTd alone following induction and consolidation therapy (odds ratio [OR], 1.60; 95% CI, 1.21-2.12; P
In May 2019, the FDA granted a priority review to the quadruplet regimen for the treatment of patients with transplant-eligible newly diagnosed multiple myeloma.
In an interview with OncLive
, Rajkumar, a professor of medicine and member of Duke Cancer Institute discussed the rapidly changing landscape for the treatment of multiple myeloma, the future of immunomodulatory drugs, and whether quadruplet regimens will become more frequent.OncLive: Are developments in multiple myeloma moving so rapidly that there is a new standard every year?Rajkumar
: Yes, whether it’s smoldering myeloma, newly-diagnosed myeloma, relapsed myeloma, things are changing really fast. We used to just watch patients with smoldering myeloma and now we are talking about treatment. We used to do VRD for induction for newly diagnosed [patients], and now we have 2 or 3 regimens that are competing with that [approach]. The same thing is happening in relapsed [myeloma]; there is an explosion of options. The standard of care seems to be changing rapidly, but it is all for the good.What framework can clinicians use to evaluate and implement emerging treatments into their practice? Are there guiding principles for when to introduce a new regimen?
You want data from good, randomized, controlled trial; that should be your guiding principle. Is whatever regimen you want to use supported by a randomized controlled trial that shows benefit? Benefit being defined as improved overall survival or improvement in patient-reported outcomes. Sometimes it is hard to get survival improvements in the newly-diagnosed setting or the smoldering myeloma setting, so you may have to rely on a surrogate endpoint, such as a minimal residual disease (MRD)-negative state or, sometimes, progression-free survival (PFS).
Other principles would be, [for example], for a relapsed patient, you have to look at the timing of the relapse, how they have done with a prior therapy, their performance status, and then make a decision on what the best regimen would be.
In general, for myeloma, we prefer a triplet regimen for frontline therapy and a triplet regimen for relapse as well. That might evolve to some high-risk patients [eventually] needing a 4-drug regimen.Are quadruplet regimens going to become more frequent in multiple myeloma?
I believe so. There have been 3 studies with quadruplets that have been reported; 2 have been published in the peer-reviewed literature and 1 has been presented in abstract form. These [studies] show better outcomes, at least in terms of target outcomes, such as response, MRD-negative rate, and PFS.
The one that really impressed me was the CASSIOPEIA trial which was recently published in the Lancet
. [Investigators] looked at a triplet VTD versus a quadruplet of daratumumab plus VTD and saw an improvement in PFS as well as a trend in improvement to overall survival. Therefore, I believe that as these data mature, we are going to start seeing more [use of] quadruplet regimens [in the treatment of these patients].