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Landgren Explains Evolving Myeloma Landscape

Angelica Welch
Published: Friday, Apr 20, 2018

C. Ola Landgren, MD, PhD
C. Ola Landgren, MD, PhD
The treatment paradigm of multiple myeloma has been flooded with new agents and combinations, as well as the potential for chimeric antigen receptor (CAR) T-cell therapy, explains C. Ola Landgren, MD, PhD.

Two- or three-drug regimens have proven to be beneficial in patients with relapsed/refractory multiple myeloma, said Landgren. The triplet of the anti-CD38 antibody daratumumab (Darzalex) with lenalidomide (Revlimid) and dexamethasone, or bortezomib (Velcade) and dexamethasone, was approved by the FDA in November 2016 for relapsed disease following at least 1 prior therapy.

The quadruplet of carfilzomib (Kyprolis), lenalidomide, dexamethasone, and daratumumab has also drawn interest in the field.

Additionally, the B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy bb2121 induced complete remissions (CRs) for 56% of patients with relapsed/refractory multiple myeloma, according to updated findings from a dose-escalation trial.

Landgren, chief of Myeloma Service at Memorial Sloan Kettering Cancer Center, discussed the treatment of patients with relapsed/refractory myeloma during the 2018 OncLive® State of the Science Summit™ on Hematologic Malignancies. In an interview during the meeting, Landgren shared his insight on CAR T-cell therapy, sequencing, and triplet and quadruplet regimens in myeloma.

OncLive: Can you please discuss your presentation?

Landgren: I gave a presentation on the treatment landscape for patients with relapsed/refractory multiple myeloma. As illustrated in my lecture, there are many options in terms of treatment. I spoke about the fact that relapse varies greatly from patient to patient. It can be a biochemical or a symptomatic relapse. Depending on how relapse presents, there are different options to consider.

For example, if the relapse is more indolent, with a biochemical presentation, many patients would choose to do a more convenient treatment. I tried to make the case that in those patients, one could argue that using the most efficacious therapies potentially could have the longest impact or best outcome, clinically. However, there are no studies looking into that. I also spoke about the relapses that are more symptomatic or more aggressive. In those instances, we probably need to use the more efficacious treatment, because we don’t really have an option.

Going forward, in terms of studies, we must focus on patients with indolent or biochemical relapses to see which of the options are the best. I outlined the fact that there are no new studies focusing on early intervention for patients who convert from minimal residual disease (MRD) negativity back to MRD positivity on clinical trials. We don’t know the answer to preventing clinical relapse, but studies in the near future hopefully will [provide it].

What was the impact of the trial of the secondgeneration CAR T-cell therapy bb2121?

I spent some time talking about the new drugs in the pipeline. The CAR T-cell therapy that targets BCMA, bb2121, was presented at the 2017 ASH Annual Meeting, and it had close to a 60% CR rate. All the current options for CAR T-cell therapy in this disease target BCMA. The sample sizes are quite small at this time and the follow-up time is restricted.

My conclusion is that it looks very exciting. We have proof of principle that the therapy actually works, but we don’t know for how long, and we need larger patient series. The 2018 ASH Annual Meeting will be very important regarding the updates for this trial.

Can you discuss the importance of optimal sequencing?

When we discuss patients with relapsed/refractory myeloma, many of the newer trials focus on patients with 1 to 3 prior lines of therapy. That is where we see a significant improvement in terms of progression-free survival. I mentioned the ASPIRE trial, which also delivered an overall survival benefit of 8 months for the 3- versus 2-drug combination. Historically, patients with relapsed disease were treated with many prior lines of therapy. That is still the case for the CAR T-cell studies that we have seen so far.




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