Meletios Dimopoulos, MD, National Kopodistrian University of Athens School of Medicine, Greece, discusses results from the phase 3 APOLLO study, which compared subcutaneous daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone for patients with relapsed/refractory multiple myeloma (MM).
These results were presented at the virtual 62nd Annual American Society of Hematology (ASH) Annual Meeting and Exposition.
Disclaimer: In discussing the applications of these data in clinical practice, Dr Dimopoulos mentioned the combination in this study is already approved in the US and he is hopeful it will be in Europe. However, the combination in this study (the subcutaneous formulation of daratumumab added to pomalidomide and dexamethasone) is not yet approved in the US or EU–it is the IV formulation of daratumumab + pomalidomide + dexamethasone that is FDA- and EMA-approved. The company did recently submit applications to regulatory authorities for this combination based on the APOLLO data (see press release here), but it is pending approval.
Transcript
I am Meletios Dimopoulos. I work at the National Kapodistrian University of Athens at the Medical School, and I am particularly interested in plasma cell dysplasias.
We know that pomalidomide and dexamethasone has been a standard of care for patients with myeloma who have been previous exposed to immunomodulatory agents such as lenalidomide and also bortezomib.
However, the outcome with this regimen is associated with a relatively short progression-free survival, so there is a need to improve upon these results. On the other hand, we know that daratumumab has single-agent activity in patients with advanced myeloma.
Also, a preliminary study, a phase 2 study which included daratumumab with pomalidomide and low-dose dexamethasone showed encouraging results. Thus, we conducted a prospective randomized study, which includes in one arm, the standard arm, pomalidomide and low-dose dexamethasone.
In the investigational arm, daratumumab was added. We had the triplet, daratumumab, pomalidomide, and low-dose dexamethasone. This study included patients who have been previously treated at least with one line of therapy, which had to include both lenalidomide and bortezomib.
What we saw is that there was a significant improvement in progression-free survival in favor of the triplet. Actually, the PFS was 12.4 months versus 6.9 months in the control arm for a hazard ratio of 0.63.
This data indicated, in the context of a prospective randomized study, that the addition of daratumumab to pomalidomide and low-dose dexamethasone was superior to pomalidomide and low-dose dexamethasone.
In particular, for patients who were refractory to lenalidomide, the results were even better with a hazard ratio of 0.36. Furthermore, there was a higher response rate in favor of the triplet at 69% versus 46% with pomalidomide and low-dose dexamethasone.
As far as toxicity is concerned, toxicities were essentially similar between the two arms with the exception of neutropenia, febrile neutropenia, and lung infections. In these categories, there was a higher incidence in the daratumumab/pomalidomide and low-dose dexamethasone.
Pomalidomide with low-dose and dexamethasone and daratumumab has been already approved in the United States. We hope that, with this prospective randomized study, this triplet combination will be approved also in Europe so there will be a greater opportunity for patients who fulfill the inclusion criteria of this study to get treated with this combination.
In this particular study, daratumumab was also given subcutaneously, and this is the first randomized study that included subcutaneous daratumumab along with other drugs. In the future, we know that daratumumab-based regimens are essentially key elements in the treatment of patients with myeloma. I believe that this combination could be used at earlier lines of therapy.
I would like to mention that, because pomalidomide and low-dose dexamethasone are given orally and because daratumumab was given subcutaneously, this regimen was convenient for the patient. Also, it saves time in the outpatient hematology/oncology units, by eliminating the IV drugs.
