Standard Induction Evolves in Transplant-Eligible and -Ineligible Multiple Myeloma

Shambavi Richard, MD

The up-front treatment of patients with multiple myeloma, whether transplant eligible or ineligible, is continuing to change as additional trials and therapies are added to the treatment landscape, according Shambavi Richard, MD, who presented on the topic during the 40th Annual Chemotherapy Foundation Symposium^®.

“Important messages relating to transplant-eligible patients [are evolving] as the standard of care [SOC] continues to change with quadruplet inductions. Moreover, transplants are still good, and therapies for consolidation after induction, as well as dual maintenance with daratumumab [Darzalex] plus lenalidomide [Revlimid] seems to be better than single-agent lenalidomide maintenance,” Richard explained. “Overall, it is important to be on the lookout for minimal residual disease [MRD]–adapted therapy. These are all updates that will be coming down the pike.”

In an interview with OncLive^® prior to her presentation, Richard discussed key studies that continue to shape the SOC in both the transplant-eligible and -ineligible populations, the role of transplant in the space, and unmet needs that remain for older and frail patients. Richard is an associate professor of medicine in hematology and medical oncology for the Center of Excellence for Multiple Myeloma at the Mount Sinai Hospital in New York, New York.

OncLive^®: What main points were conveyed in your presentation during the meeting?

Richard: My presentation covered frontline therapy for patients with newly diagnosed, transplant-eligible and -ineligible multiple myeloma. I began my talk with the role of transplant, the various induction therapies, and what is now becoming the standard for induction treatment. Moreover, I touched a bit on MRD-adapted therapies.

[In the transplant-eligible population,] the key points I covered are in relation to the emergence of quadruplet therapy as the new SOC for induction, and that transplants are still alive today. For transplant-ineligible patients, daratumumab, lenalidomide, and dexamethasone [DRd] has become the new standard.

Could you elaborate on the use of DRd in the frontline setting for patients with transplant-ineligible multiple myeloma?

Frontline treatment with DRd was evaluated in the phase 3 MAIA trial [NCT02252172] and was intended for transplant-ineligible patients. The median age of patients on the trial was 73 years, representing an older group.

Patients were randomized to DRd or lenalidomide and dexamethasone. The results showed a significant improvement in the median progression-free survival [PFS] for the experimental group––unprecedented results that are approaching the kinds of numbers that we are seeing for transplant-eligible patients. As such, this regimen has become the new standard.

How has the GRIFFIN trial affected frontline treatment for patients who are eligible for transplant?

It used to be that we would give triplets as induction therapy followed by transplant for newly diagnosed patients who were transplant eligible. However, now, with the phase 2 GRIFFIN trial [NCT02874742] results that have shown excellent response rates, as well as good PFS improvements, daratumumab, lenalidomide, bortezomib [Velcade], and dexamethasone is now the new SOC.

Transplant following quadruplet induction and maintenance therapy, such as dual maintenance, is now becoming the standard. This approach is leading to improved outcomes vs the previous approach of triplet induction, transplant, and single-agent lenalidomide maintenance.

What unmet needs remain for patients with multiple myeloma?

We want to continue the quest of curing multiple myeloma and we want to see a plateau in the survival curve, regardless of transplant status. We also want patients to live longer and have a good quality of life while they live longer.

Other unmet needs include those who are high risk or frail. It is hard for these patients to receive each subsequent line of therapy, so we need to use our best approaches up front. Being able to give fewer lines of therapy that are more effective than sequenced approaches is the best way to go with any patient, but specifically for transplant-ineligible patients, because they [have a higher attrition rate than younger patients].

What clinical trials have the potential to inform the future of clinical practice?

For the transplant-eligible group, the pivotal study that has changed practice is the GRIFFIN trial, and we look forward to seeing the results from the phase 3 PERSEUS trial [NCT03710603].

The MAIA trial has changed practice for transplant-ineligible patients. Moreover, the phase 2 MASTER trial [NCT03224507] continues to educate us on how to use MRD to adapt therapy, which is exciting. Another anticipated trial that will be coming down the pike is the phase 3 DRAMMATIC trial [NCT04071457].