Dr Yee on Daratumumab/Lenalidomide With Ixazomib/Dexamethasone in Multiple Myeloma

“[We saw] high overall response rates which translated to a [12-month] PFS [rate] of 92.4%.”

Andrew Yee, MD, the clinical director of the Center for Multiple Myeloma at Massachusetts General Hospital and an assistant professor of medicine at Harvard Medical School, discussed findings from a phase 2 study (NCT04009109) of lenalidomide (Revlimid) plus ixazomib (Ninlaro),​dexamethasone, and daratumumab (Darzalex) for the treatment of patients with newly diagnosed multiple myeloma, which were presented during the 

 International Myeloma Society Meeting and Exposition

The intended patient population of the phase 2 study was approximately 188 patients, but accrual was affected by the COVID-19 pandemic, Yee began. The study was able to enroll 79 patients, all of whom received the same treatment regimen of 12 cycles of daratumumab at 1800 mg via a conventional schedule, lenalidomide at 15 mg on days 1 through 21, ixazomib at 4 mg on days 1, 8, and 15, and weekly dexamethasone, he continued. After 1 year, patients were randomly assigned to maintenance therapy with lenalidomide or daratumumab plus lenalidomide and ixazomib, he added. The primary end point was progression-free survival (PFS), he noted. 

Following 1 year of treatment, patients (n = 79) achieved an overall response rate of 92.4% (95% CI, 84.2%-97.2%), Yee said. The very good partial response (VGPR) or better and complete response (CR) or better rates were 69.6% (95% CI, 58.3%-79.5%) and 22.8% (95% CI, 14.1%-33.6%), respectively. The CR and VGPR rates were 15.2% and 46.8%, respectively. Three patients achieved a stringent CR and 18 experienced a partial response.

Additionally, the high response rate translated into a 12-month PFS rate of 92% (95% CI, 86.1%-98.4%), Yee said, noting that this finding was similar to that of standard-of-care approaches with significantly lower rates of neutropenia.

Yee concluded that these findings show that the regimen can be adapted for use in older, more frail patients to make for a more favorable patient experience, without compromising efficacy.

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Andrew Yee, MD, discusses lenalidomide plus ixazomib,​ dexamethasone, and daratumumab in newly diagnosed multiple myeloma.

Andrew Yee, MD, clinical director, Center for Multiple Myeloma, Mass General Brigham, Massachusetts General Hospital, assistant professor of medicine, Harvard Medical School, discusses treating patients with relapsed disease in multiple myeloma.

When treating patients with relapsed disease, it is important to consider how long their response to their initial therapy lasted, Yee says. Moreover, the type of relapse is important to account for, as some patients may have a biochemical relapse as compared with a relapse that manifests as pain from lytic bone disease or fatigue from cytopenias or renal dysfunction, Yee explains.

A more intensive approach may be necessary for patients with symptomatic relapses compared with a biochemical relapses, Yee continues. Overall, oncologists should utilize their best treatments first, rather than save them for relapse, Yee concludes. 

Andrew Yee, MD, discusses treating patients with relapsed disease in multiple myeloma.


Dr. Yee on Treating Patients with Relapsed Disease in Multiple Myeloma

Andrew Yee, MD, an assistant professor of medicine at Harvard Medical School and a hematologist/oncologist with the Center for Multiple Myeloma at the Massachusetts General Hospital, discusses the utility of isatuximab-irfc (Sarclisa) in relapsed/refractory multiple myeloma.

Isatuximab is an anti-CD38 monoclonal antibody that has shown utility within the multiple myeloma space, says Lee. The more options that are available in the field, the better it is for patients with the disease, adds Lee, as multiple myeloma can be a complicated disease with different types of relapses.

ICARIA-MM was the first randomized phase 3 study to demonstrate the value of adding an anti-CD38 monoclonal antibody to pomalidomide (Pomalyst) and dexamethasone, says Lee. This agent is being utilized within the relapse setting, adds Lee. However, at this time, it is unknown whether there is any specific, clinical difference between this agent and daratumumab (Darzalex). That being said, any scenario where daratumumab can be used, isatuximab is also a viable option, says Lee.

No specific clinical reason exists to choose one over the other, but it is helpful that the field has a phase 3 trial to demonstrate the efficacy of the combination of isatuximab with pomalidomide and dexamethasone, concludes Lee.

Andrew Yee, MD, discusses the utility of isatuximab-irfc in relapsed/refractory multiple myeloma.

Dr. Yee on the Utility of Isatuximab in Combination Therapy for Relapsed/Refractory Myeloma

In the phase 3 CANDOR trial, investigators examined the combination of carfilzomib (Kyprolis), daratumumab (Darzalex), and dexamethasone versus carfilzomib/dexamethasone alone in patients with relapsed/refractory multiple myeloma, says Yee. One thing to note is that this trial was for patients who received 1 to 3 prior lines of treatment, and the carfilzomib regimen was administered on a twice-a-week schedule.

Results from the trial showed that the triplet regimen resulted in significant improvement in high-quality responses, as well as a significant improvement in progression-free survival (PFS) when compared with the doublet regimen, adds Ye. The median PFS was not reached for the triplet arm versus 15.8 months for the doublet arm (HR, 0.63; 95% CI, 0.46-0.85; 

Like all treatments that are available, approaches must be tailored to patients and their preferences, adds Ye. For patients who might have trouble obtaining pomalidomide (Pomalyst) due to, for example, financial issues, this triplet regimen can serve as an excellent option without too much out-of-pocket cost, concludes Yee.

Andrew Yee, MD, discusses the phase 3 CANDOR trial in relapsed/refractory multiple myeloma.

Dr. Yee on the Results of the CANDOR Trial in Relapsed/Refractory Myeloma


Andrew Yee, MD, assistant professor of medicine, Harvard Medical School, hematologist/oncologist, Center for Multiple Myeloma, Massachusetts General Hospital, discusses trials evaluating treatment for patients with lenalidomide (Revlimid)-refractory multiple myeloma.

In the phase 3 OPTIMISMM trial, the overall response rate was 82.2% with the triplet combination of pomalidomide (Pomalyst), bortezomib (Velcade) and dexamethasone compared with 50.0% with bortezomib/dexamethasone alone in patients with relapsed/refractory multiple myeloma who received 1 to 3 prior lines of therapy, including a lenalidomide-containing regimen.

Additionally, the median progression-free survival was 11.2 months with the triplet versus 7.1 months with the doublet (HR, 0.61; 95% CI, 0.49-0.77; 

 <.0001).

The results of the OPTIMISMM trial have opened the door for other pomalidomide-containing triplet regimens in this space, concludes Yee.

Andrew Yee, MD, discusses trials evaluating treatment for patients with lenalidomide-refractory multiple myeloma.

Dr. Yee on Trials Evaluating Treatment in Lenalidomide-Refractory Multiple Myeloma

Andrew Yee, MD, assistant professor of medicine, Harvard Medical School, hematologist/oncologist, Center for Multiple Myeloma, Massachusetts General Hospital, discusses the role of carfilzomib (Kyprolis) in relapsed/refractory multiple myeloma.

Carfilzomib has demonstrated utility as a single agent and in doublet and triplet regimens for patients with relapsed/refractory multiple myeloma.

For example, findings from the phase 3 ENDEAVOR trial demonstrated superior progression-free survival and overall survival with the combination of carfilzomib and dexamethasone compared with the combination of bortezomib (Velcade) and dexamethasone in the relapsed/refractory setting. Additionally, carfilzomib is associated with a lower risk of peripheral neuropathy compared with bortezomib, says Yee.

Data from the phase 3 CANDOR trial showed that the addition of daratumumab (Darzalex) to carfilzomib/dexamethasone reduced the risk of disease progression or death for patients with relapsed/refractory disease compared with carfilzomib/dexamethasone alone.

Additionally, data from the phase 3 ARROW study showed that carfilzomib dosed once weekly at 70 mg/m

 improved progression-free survival compared with the standard twice-weekly dose of 27 mg/m

As such, the platform for triplet-based combinations and weekly dosing of carfilzomib has become the foundation for future investigational efforts, concludes Yee.

Andrew Yee, MD, discusses the role of carfilzomib in relapsed/refractory multiple myeloma.

Dr. Yee on the Role of Carfilzomib in Relapsed/Refractory Multiple Myeloma

Andrew Yee, MD, assistant professor of medicine, Harvard Medical School, hematologist/oncologist, Center for Multiple Myeloma, Massachusetts General Hospital, discusses treatment considerations in relapsed/refractory multiple myeloma.

It is important to tailor an individual’s treatment based on the type of relapse they are experiencing, says Yee.

In the majority of cases, patients will have a biochemical relapse defined by elevated monoclonal protein or free light chain, explains Yee. For these patients, less intensive therapy with corticosteroids or oral agents should be considered.

Alternatively, patients who have a more aggressive relapse with high-risk features such as lytic bone lesions, a dramatic increase in monoclonal protein, or high-risk fluorescence in situ hybridization should be considered for more intensive therapy with triplet therapy, concludes Yee.

Andrew Yee, MD, discusses treatment considerations in relapsed/refractory multiple myeloma.

Andrew Yee, MD

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