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Treatment for Newly Diagnosed Patients Shifts Across Myeloma Spectrum

Caroline Seymour
Published: Wednesday, Feb 13, 2019

Jesus Berdeja, MD
Jesus Berdeja, MD
There has been no shortage of data in the setting of newly diagnosed multiple myeloma, explained Jesus Berdeja, MD. Research has ranged from exploration of more intensive regimens in transplant-ineligible patients to that of quadruplet regimens in transplant-eligible patients. 

Data from the phase III MAIA trial demonstrated a 44% reduction in the risk of disease progression or death with the combination of daratumumab (Darzalex), lenalidomide (Revlimid), and dexamethasone (DRd) versus lenalidomide and dexamethasone (Rd) in transplant-ineligible patients.1 Moreover, an FDA supplemental biologics license application was initiated in January 2019 for this regimen.

“So many different treatments have been studied in the relapsed/refractory setting and are finally making their way to the newly diagnosed patient,” said Berdeja. “How to best use them and combine them is an ongoing process."

In the transplant-eligible population, quadruplet regimens are becoming more prominent, evidenced by the recent data with daratumumab plus bortezomib (Velcade), lenalidomide, and dexamethasone (VRd). According to findings from the run-in phase of an open-label study, the regimen induced a stringent complete response (sCR) or CR in 63% of patients by the end of consolidation therapy.2

Moreover, 2-year maintenance therapy with ixazomib (Ninlaro) was associated with a 39% improvement in progression-free survival (PFS) over placebo in patients who achieved a partial response to induction therapy with a proteasome inhibitor (PI) and/or an immunomodulatory agent, according to results from the phase III TOURMALINE-MM3 trial.3

In an interview during the 2019 OncLive® State of the Science Summit™ on Hematologic Malignancies, Berdeja, the director of Multiple Myeloma Research at Sarah Cannon Research Institute, discussed emerging standards of care in transplant-eligible and -ineligible patients with newly diagnosed multiple myeloma.

OncLive®: What are some emerging developments in the newly diagnosed setting of multiple myeloma?

Berdeja: When a patient is diagnosed with multiple myeloma, we have to decide whether or not they are a transplant candidate. There are some differences in opinion, but ultimately, we all have a way to decide who is transplant-eligible and who is transplant-ineligible.

In the past, the treatment paradigm for transplant-ineligible patients was relatively poor. Those patients were felt to be frail, and they were often treated less aggressively than they probably could have been treated. We're starting to see that there is a benefit to combination therapies [beyond] older doublet combinations. We're realizing that standard treatments like bortezomib, melphalan, and prednisone (VMP) and Rd are not the best options for patients.

The biggest advance has been the incorporation of the monoclonal antibodies—specifically daratumumab, which has significantly improved outcomes for these patients and added very little toxicity. We need to assess the long-term data, but [this approach] looks very promising.

In the transplant-eligible population, patients have always been treated relatively aggressively; I would argue that for the most part that [only applies to] induction. Often, we de-escalate therapy a lot more than we do with transplant-ineligible patients. We're starting to see more incorporation of quadruplets or perhaps consolidation later on. There's still an open question of whether 1 transplant is sufficient as compared with 2 transplants.

We're starting to see really strong combinations such as carfilzomib (Kyprolis), lenalidomide, and dexamethasone (KRd), or even KRd plus daratumumab, and VRd plus daratumumab in this patient population. [We’re getting to the point where we can ask] whether we need transplant at all. [We think we figured it out that we don’t], and then all of a sudden [we realize that] adding high-dose melphalan is still important. At this point, it’s still the standard of care in those patients.


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