In an interview with Targeted Oncology, Noa Biran, MD, discussed the findings from 2 clinical trials evaluating consolidation therapy post-transplant in patients with high-risk multiple myeloma.
Noa Biran, MD
At the 2019 American Society of Hematology (ASH) Annual Meeting, a number of abstracts looked at different maintenance and consolidation treatment options for patients with multiple myeloma following autologous stem cell transplant (ASCT). Among these was a study of elotuzumab (Empliciti) plus lenalidomide (Revlimid) and dexamethasone as consolidation post-ASCT, which induced a promising progression-free survival (PFS) rate in high-risk patients.
Overall, 31 patients were analyzed in a retrospective study. The data demonstrate a PFS of 31.4 months in patients with high-risk multiple myeloma when they received initial treatment with elotuzumab plus lenalidomide and dexamethasone or elotuzumab plus pomalidomide (Pomalyst) and dexamethasone after ASCT at a fixed dose for 4 cycles.
With this consolidation regimen, investigators noted that the treatment was generally well-tolerated. Some hematologic adverse events (AEs) were observed, but no serious immune-mediated AEs occurred in this patient population.
In addition to this study, data from a 2-year update on the phase II trial of pembrolizumab (Keytruda), lenalidomide, and dexamethasone as post-ASCT consolidation therapy were also presented. These data demonstrate a median PFS of 27.6 months compared with the historical control of 8 to 14 months. However, this trial was previously placed on a clinical hold by the FDA and remains on hold.
In an interview withTargeted Oncology, Noa Biran, MD, an attending physician at the John Theurer Cancer Center, discussed the findings from 2 clinical trials evaluating consolidation therapy post-transplant in patients with high-risk multiple myeloma. She also highlighted findings from a study evaluating the value of digital patient reported outcomes (PROs) for long-term management of treatment fatigue in relapsed/refractory disease.
TARGETED ONCOLOGY: What was the rationale for evaluating elotuzumab as post-ASCT consolidation therapy in patients with high-risk multiple myeloma?
Biran:Patients with high-risk multiple myeloma have very short remissions post-ASCT, and the hypothesis was that we could take the disease at the lowest burden of disease state at a time of immune recovery and harness that immune recovery post-ASCT. That is where elotuzumab fit in because we want to use a therapy that can increase the natural killer cell activity and the T cell activity in combination with an immunomodulatory therapy and steroid to reduce disease burden and prolong PFS post-ASCT. That was the rationale for combining elotuzumab with lenalidomide and dexamethasone.
TARGETED ONCOLOGY: How was the trial designed, and what were the findings?
Biran:This study was a retrospective study. It was a single-institution study, and we looked at 31 patients with high-risk multiple myeloma defined by current International Myeloma Working Group criteria for high risk. They received a fixed 4 of cycles of elotuzumab, lenalidomide, and dexamethasone, then 2 patients received elotuzumab, pomalidomide, and dexamethasone post-ASCT. The steroids were reduced after the first 2 cycles or discontinued in most cases.
Most patients did very well. The median PFS was 31.4 months. In a high-risk population with fixed-dose therapy, not continuous therapy, this is quite a remarkable median PFS. This is a retrospective study, so we need to take it into perspective and perhaps use it as a basis for future prospective studies.
TARGETED ONCOLOGY: Could you discuss the findings from the 2-year update on the phase II trial of pembrolizumab, lenalidomide, and dexamethasone as post-ASCT consolidation therapy?
Biran:We are seeing very good results in a small number of patients. Due to the FDA hold on pembrolizumab in combination with IMIDs in multiple myeloma, the study was stopped early. However, we have 12 evaluable patients who received therapy with pembrolizumab, lenalidomide, and dexamethasone as post-ASCT consolidation. We are seeing in a high-risk subset a median PFS of 27.5 months, which is quite remarkable. Patients who have high-risk disease without lenalidomide maintenance have been reported to have a median PFS of 8 to 14 months.
This is exceeding historical expectations of post-ASCT therapies in high-risk patients with multiple myeloma. The real side effects we saw were manageable. We saw some cytopenias and increased risk of infections, but we did not see any serious immune-mediated AEs that would flag this as a high-risk regimen in terms of toxicity.
TARGETED ONCOLOGY: In regard to your presentation on PROs for long-term management of treatment fatigue in relapsed/refractory disease, what were the findings from this analysis?
Biran:The purpose of this study was to track PROs and to identify unmet needs from the patient’s point of view. The patients received a digital platform in which they could communicate ad-hoc their symptoms to our clinic. We learned a lot about our workflow and how to integrate a platform like this into the clinic workflow. It is very difficult to do this, and it was much harder than we expected. In terms of communicating to the clinic, it has to be done in a very individual setting for the clinical setting, and it has to work into the clinic flow, not an addition.