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Myeloma Expert Highlights Practice-Changing ASH Findings

Gina Columbus @ginacolumbusonc
Published: Thursday, Dec 29, 2016

C. Ola Landgren, MD, PhD

C. Ola Landgren, MD, PhD

The landscape of multiple myeloma continues to shift with more drug approvals, but pivotal results out of the 2016 ASH Annual Meeting will likely alter it even further, according to C. Ola Landgren, MD, PhD.

Regarding the monoclonal antibody daratumumab (Darzalex), updated results from the phase III CASTOR and POLLUX studies continued to show positive results in patients. In CASTOR, daratumumab was added to a backbone of bortezomib (Velcade)/dexamethasone while the POLLUX trial investigated the monoclonal antibody with lenalidomide (Revlimid)/dexamethasone.

Additionally, interim findings of an investigational anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy also showed encouraging, yet early, activity in patients with relapsed/refractory multiple myeloma (NCT02658929).

Venetoclax (Venclexta), a BCL-2 inhibitor already FDA approved in the space of chronic lymphocytic leukemia (CLL), was also found to have notable findings in myeloma abstracts presented at the meeting, Landgren explains.

Landgren gave a lecture on these exciting studies and more in multiple myeloma during the 2016 OncLive® State of the Science Summit on Hematologic Malignancies.

In an interview during the meeting, Landgren, chief of Myeloma Service at Memorial Sloan Kettering Cancer Center, picks apart some of the top presented abstracts in multiple myeloma from the 2016 ASH Annual Meeting, as well as what’s in store for the field.

OncLive: Can you provide an overview of your lecture in myeloma?

Landgren: It included selected highlights from the 2016 ASH Annual Meeting. I first talked about the updated CASTOR and POLLUX studies that are based on daratumumab, both in combination with lenalidomide/dexamethasone and bortezomib/dexamethasone in the 2 studies, respectively. These combos were recently FDA approved for patients with 1 or more prior lines of therapy.

The presentation today was an update on the follow-up with particular focus on minimal residual disease (MRD) status. It shows the patients can obtain MRD negativity on both the experimental arm and the control arm. Patients treated with or without daratumumab on both of these studies obtained MRD negativity, but the rate of MRD negativity is higher in the experimental arm in both studies.

Secondly, there was an update on CAR T-cell therapy. At ASH, we heard from the BCMA CAR T-cell therapy regarding the first 9 patients treated in the first cohort.

The third is the use of venetoclax, an oral BCL-2 inhibitor. It was recently approved for other B-cell malignancies. There was updated information on single-drug use in a phase I trial for patents with myeloma. In patients with an 11;14 translocation who typically have activation of BCL-2, they seem to have pretty good response to this drug.

We have heard about the POLLUX/CASTOR studies often. What questions still need to be answered regarding those studies?

It is very exciting to see how the monoclonal antibodies are coming at full speed into the myeloma field. The FDA approved the use of daratumumab as a single agent in November 2015 and now the agency gave approval of daratumumab in combination with lenalidomide/dexamethasone and bortezomib/dexamethasone, which is exactly what the CASTOR and POLLUX studies show.

It is definitely changing the treatment landscape here in the United States. A lot of patients will start receiving monoclonal antibodies as their relapsed treatment. They probably will be treated, if they come to academic centers, typically with 3-drug combinations, an immunomodulatory (IMiD) proteasome inhibitor, and a low-dose steroid with or without transplant. If they relapse, then daratumumab in combination with either lenalidomide/dexamethasone or bortezomib/dexamethasone are very valid options. That will change the field.

I would like to emphasize that a lot of the other options remain very valid, as well. The ASPIRE, TOURMALINE-MM1, and ELOQUENT trials are also comprised of regimens that are other great options.

What challenges are oncologists still facing with these daratumumab regimens?

Daratumumab is a very well-tolerated drug. I prescribe it a lot; I see a lot of patients myself. One of the key problems, if we use the word problem, is that the first infusion can take a little while. That is because patients can have infusion reactions. Typically, if patients have infusion reactions, it typically will involve some shortness of breath, swelling in the mouth, itching, or a drop in blood pressure.

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