Noa Biran, MD
Although there is still a gap in physicians’ treatment arsenal for high-risk patients with multiple myeloma, that is not to discount the great strides physicians have made in the landscape, explains Noa Biran, MD.
For example, results from the SWOG S0777 trial confirmed the superiority of triplet regimens to doublets in the newly diagnosed setting, said Biran. The benefit in progression-free survival (PFS) and overall survival (OS) extended to both transplant-eligible and transplant-ineligible patients who were randomized to upfront bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone versus lenalidomide and dexamethasone alone. The median PFS was 43 months versus 30 months with the bortezomib and lenalidomide/dexamethasone-alone arms, respectively; moreover, median OS was 75 months with the addition of bortezomib versus 64 months with lenalidomide/dexamethasone alone.
“There's a deepening response over time in [many triplet] regimens,” said Biran.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Hematologic Malignancies, Biran, of the Myeloma Division at John Theurer Cancer Center, discussed treatment breakthroughs and emerging advances in the field of multiple myeloma.
OncLive: How has the treatment for newly diagnosed multiple myeloma evolved?
: There are several different areas including transplant-eligible patients, transplant- ineligible patients, and the role of transplant. In the newly diagnosed setting, triplets are better than doublets in both patient populations. They achieve a very rapid and deep response. That usually translates into a longer duration of remission. The SWOG S0777 trial randomized patients who did not go onto transplant to either upfront bortezomib, lenalidomide, and dexamethasone, or lenalidomide and dexamethasone alone. The patients who received the triplet had a much longer PFS and OS. It’s important to keep transplant-ineligible patients on a triplet regimen.
In the transplant setting, the EMN02/HO95 study looked at a single versus double transplant and showed an improvement in PFS [with double transplant]. This extended to patients who received tandem transplant and was seen especially in high-risk patients.
Daratumumab (Darzalex) plus bortezomib, melphalan, and prednisone (VMP) is up for FDA approval. How will this therapy impact the landscape?
In the United States, melphalan is not used very commonly in the upfront setting, even in transplant-ineligible patients. I'm not sure if that particular regimen will change the treatment landscape. However, it may translate into the use of upfront daratumumab in a triplet regimen in transplant-ineligible patients. There are several studies that are evaluating that. The MAIA study is looking at daratumumab, lenalidomide, and dexamethasone in transplant-ineligible patients. Those results are more likely to change the treatment landscape in the United States.
Will newly diagnosed patients benefit from the January 2018 FDA approval of denosumab (Xgeva)?
Absolutely. Denosumab was recently approved for patients with bone lesions. The published study was a noninferiority trial comparing denosumab with zoledronic acid in patients with multiple myeloma. Denosumab was noninferior in the primary endpoint of skeletal-related events (SREs). The secondary endpoint also showed a slight PFS advantage.
Denosumab is a RANK-Iigand inhibitor—not a bisphosphonate—so it's not cleared by the kidneys. Around 40% of patients with multiple myeloma have renal insufficiency at diagnosis, so this treatment aids in improving bone strength and decreasing SREs without compromising renal function. It's going to be very important for our patients with renal insufficiency who have lytic lesions, or other bone related lesions at diagnosis.
How can interventions with antibiotics and influenza vaccines supplement therapies?
Infections are very common in patients with multiple myeloma. Most people with the disease die from an infection rather than from the disease itself. Everybody who is on a proteasome inhibitor should be on a prophylaxis with acyclovir or valacyclovir and should remain on that for at least 3 months following the last dose of the proteasome inhibitor.