Sameh Mikhail, MD
Daratumumab (Darzalex), an anti-CD38 monoclonal antibody, has demonstrated high response rates in patients with relapsed or refractory multiple myeloma, with the pivotal phase III CASTOR and POLLUX studies exploring the agent in combination.
In the CASTOR trial, daratumumab was added to bortezomib (Velcade) and dexamethasone. Results showed that the regimen reduced the risk of progression or death by 61% versus the 2 drugs alone for patients with recurrent/refractory multiple myeloma.1
Likewise, the addition of daratumumab to lenalidomide (Revlimid) and dexamethasone showed similar success in the POLLUX trial, with a reduction in the risk of progression or death by 63% with daratumumab plus the 2 drugs versus lenalidomide and dexamethasone alone.2
During the 2017 OncLive®
State of the Science SummitTM
on Hematologic Malignancies, Sameh Mikhail, MD, a medical oncologist at the Mark H. Zangmeister Cancer Center, Mount Carmel Health System, covered the impact of these trials on the treatment landscape of multiple myeloma. In an interview during the meeting, he discussed the promise of daratumumab, as well as the potential of medical marijuana to curb the adverse events (AEs) seen with potent anticancer drugs.
OncLive: Can you touch on the importance of the CASTOR and POLLUX studies?
The CASTOR and POLLUX trials were 2 recent trials that were very well received in the medical community. They introduced a new agent, daratumumab, in combination with commonly used myeloma therapy, such as bortezomib and lenalidomide. The 2 trials had similar designs; they included regimens of bortezomib and dexamethasone either alone or in combination with daratumumab, or lenalidomide plus dexamethasone with or without daratumumab. Both trials were conducted in patients with relapsed or refractory multiple myeloma.
The results were very striking and showed very high response rates. In combination with lenalidomide and dexamethasone, the response rate was close to 90% with progression-free survival at 1 year of about 80%. In the relapsed and refractory setting, these are very encouraging results. The side effect profile was, overall, very manageable. The most common toxicity was infusion reactions, which were mostly grade 1/2 with daratumumab.
Daratumumab is an antibody that targets CD38, and CD38 is present on neutrophils and lymphocytes in addition to plasma cells. Therefore, the AEs were mostly related to cytopenias. What is interesting about daratumumab is that it has single-agent activity, as well.
What do you believe is that most important thing that community oncologists should know about daratumumab?
The most important thing to know is that the AEs have been grade 1 or 2 and are not serious reactions. Also, what I like as a community physician is that the schedule for daratumumab is very patient friendly; it is given weekly, and then every 2 weeks, and then every 4 weeks. This has been a challenge in myeloma therapy where patients must come several times a week for treatment.
Are there any other ongoing studies in multiple myeloma that are particularly interesting?
Now, a lot of studies are looking at the inclusion of stem cell transplant, and the timing of stem cell transplant in patients with multiple myeloma. There are a lot of a lot of immunomodulatory agents that are being investigated, as well as new combinations.