Expert Discusses Novel Treatment Options in Multiple Myeloma

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

OncLive: Can you touch on the importance of the CASTOR and POLLUX studies?

During the 2017 OncLive^® State of the Science Summit^TM 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.Mikhail: 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.

What do you believe is that most important thing that community oncologists should know about daratumumab?

Are there any other ongoing studies in multiple myeloma that are particularly interesting?

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.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.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.

What are your thoughts on the clinical trials that were halted in multiple myeloma with checkpoint inhibitors?

Can you discuss some of the news that has come out recently about medical marijuana in cancer care?

One of the areas that we are all looking out for is the use of immunotherapy in multiple myeloma. There are some safety concerns that are being investigated, but immunotherapy has encouraging results in other settings. Therefore, we are all very anxious to see whether immunotherapies will be included as part of myeloma therapy or not. I was not aware of any safety concerns in phase I trials with immunotherapy. But then with the later-phase trials, safety concerns began to be more noticeable. Therefore, one of the questions is whether immunotherapy should be used as a single agent, and maybe in combination is where some of the toxicities become more noticeable. Or, perhaps that was a false alarm. We are all anxiously awaiting this analysis.This is an area that I find very interesting; I receive at least 1 question from patients every day about it. There has been a lot of information in the press about the benefits of marijuana in dealing with cancer-related symptoms, such as decreased appetite. We definitely think there is going to be room for using marijuana in our day-to-day practice. The questions are, “How is it going to be regulated and how is it going to be prescribed?”

If it becomes available, how do you see it altering the future of the treatment of patients with cancer, especially hematologic malignancies?

It has been legalized in medical practice in Ohio, but there are no dispensaries yet. Therefore, it is legal but not available. A lot of it will depend on the regulations, pricing, how easily it can be prescribed, and how easily it can be obtained. For every practicing oncologist who is managing patient symptoms, improving their quality of life is a priority. We always welcome any new modality that would help patients with their quality of life.

Is there anything else you would like to add?

Most treatments can cause nausea and depressed appetite, so the use of marijuana could eventually be seen across hematologic malignancies, as well as solid tumors. One of the areas that has gained a lot of interest in the oncology world is targeted therapies. This is an area that I have worked in for some time, using platforms that evaluate for targets in the community setting. The good news is that such platforms for evaluating targetable mutations are now commercially available, so it can be used by the community oncologist. In many cancers, there is a direct impact on selection of treatments for patients. Fifty years from now, this is going to be our day-to-day practice, so it is considered an evolving field.

References

1. Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(8):754-766. doi: 10.1056/NEJMoa1606038.
2. Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375(14):1319-1331. doi: DOI: 10.1056/NEJMoa1607751.