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Venetoclax Triplet Shows Promise in Relapsed/Refractory Multiple Myeloma

Jason Harris
Published: Friday, Aug 31, 2018

Luciano Costa, MD, PhD
Luciano Costa, MD, PhD
The combination of venetoclax (Venclexta), carfilzomib (Kyprolis), and dexamethasone may provide a new treatment option for patients with relapsed/refractory multiple myeloma, according to Luciano J. Costa, MD, PhD.

, Costa discussed the emerging potential of combing venetoclax with carfilzomib and dexamethasone as a treatment for patients with relapsed/refractory multiple myeloma.

OncLive: Can you provide an overview of the phase II triplet study?

Costa: We presented phase II results of a combination of venetoclax, carfilzomib, and dexamethasone in patients with relapsed/refractory multiple myeloma. This study was done across multiple institutions in the United States. We accrued 42 patients, and we presented safety data on those 42 patients and efficacy data on a subset of 30 patients who were enrolled 3 or more months prior to the data cutoff.

The combination was overall well tolerated. The safety profile was very similar to what was seen in prior carfilzomib studies, but also what we are familiar with in clinical practice. We had mostly cytopenias that were asymptomatic. We had a few cardiovascular events, including a low rate of congestive heart failure and some patients developed hypertension. For the most part, the cardiovascular toxicities were reversible once carfilzomib was held. Some of those patients were able to resume carfilzomib at a reduced dose.

What did you find in terms of efficacy?

What we found was very intriguing. We saw a high rate of response. We had an 83% response rate across the subset of patients. Keep in mind, this is a subset of patients with a median of 2 prior lines of therapy, with half of patients being refractory to prior bortezomib and two-thirds were refractory to prior immunomodulatory (IMiDs) agents. The majority of patients on trial were refractory to their last line of therapy.

Interestingly, we saw equally high response rates for patients who were refractory to IMiDs or proteasome inhibitors at greater than 80%. Being refractory to prior agents did not seem to affect the likelihood of responding to the combination.

Venetoclax has been particularly active in prior studies among patients with t(11;14) myeloma. That is a population in which venetoclax has relatively high single-agent activity. In this trial, we saw that among the 7 patients with t(11;14) disease, they all had a response. Six of those 7 patients had VGPR or better.

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Online CME Activities
TitleExpiration DateCME Credits
Advances in™ Multiple Myeloma: Changing Treatment Paradigms and the Emerging Potential of CAR T-Cell TherapyAug 30, 20191.5
2nd Annual Live Medical Crossfire®: Hematologic Malignancies OnlineSep 28, 20198.0
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