Rebecca Silbermann, MD, MMS, an assistant professor of medicine, Division of Hematology/Medical Oncology, School of Medicine, Oregon Health & Science University, discusses the phase 3 CASTOR trial in relapsed/refractory multiple myeloma.

The CASTOR study enrolled 498 patients, says Silbermann. Data were initially presented at the end of 2015 and were published in 2016; they showed that the combination of daratumumab (Darzalex), bortezomib (Velcade), and dexamethasone was beneficial for patients who had received at least 1 prior line of therapy and achieved at least a partial response to that treatment. Patients who were refractory to proteasome inhibitors were excluded from the study.

The initial analysis had a median follow-up of 7.4 months, adds Silbermann. The more recent data provided a median of 40 months of follow-up, and also included a subgroup analysis on standard-risk versus high-risk patients and how those patients did with the regimen. Results showed that even patients with high-risk disease did well with the approach, and they experienced a significant improvement in progression-free survival (PFS) for the daratumumab combination arm. The median PFS in the standard-risk patients was about 16.7 months with the triplet versus 7.1 months for the doublet combination, concludes Silbermann.

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Rebecca Silbermann, MD, MMS, discusses the phase 3 CASTOR trial in relapsed/refractory multiple myeloma.

Dr. Silbermann on the CASTOR Trial in Relapsed/Refractory Myeloma

Rebecca Silbermann, MD, MMS, assistant professor of medicine, Division of Hematology/Medical Oncology, School of Medicine, Oregon Health & Science University, discusses the role of disease biology in multiple myeloma. 

Despite significant research efforts, questions regarding the heterogeneity of multiple myeloma remain, Silbermann says. In the coming years, it is likely that multiple disease subtypes will be identified, explains Silbermann. 

At the time of diagnosis and relapse, ​understanding the patient’s individual disease biology plays a crucial role in treatment selection, ​says Silbermann.

For example, ​treatment considerations upon relapse differ among patients with symptomatic, high-risk multiple myeloma and patients with standard-risk, well-controlled disease. ​Likewise, a patient with standard-risk multiple myeloma who had difficulty achieving first remission should be carefully evaluated to determine whether their disease biology necessitates more aggressive subsequent therapy.

Rebecca Silbermann, MD, MMS, discusses the role of disease biology in multiple myeloma. 

Dr. Silbermann on the Role of Disease Biology in Multiple Myeloma 

Rebecca Silbermann, MD, MMS, assistant professor of medicine, Division of Hematology/Medical Oncology, School of Medicine, Oregon Health & Science University, discusses current treatment options for fit patients with multiple myeloma who experience early relapse.

In patients who may be sensitive to immunomodulatory drugs (IMiDs), lenalidomide (Revlimid) could be considered as part of a triplet regimen, Silbermann says. For example, lenalidomide in combination with daratumumab (Darzalex) and dexamethasone has demonstrated efficacy in this setting. 

Similarly, patients who are unlikely to respond to IMiDs could be considered for triplet therapy with a proteasome inhibitor (PI) such as bortezomib (Velcade), Silbermann explains. The phase 3 CASTOR trial demonstrated significantly longer progression-free survival with bortezomib plus daratumumab and dexamethasone compared with bortezomib and dexamethasone alone. 

Additionally, carfilzomib (Kyprolis), another PI, could be considered based on findings from the phase 3 ENDEAVOR trial, which showed that carfilzomib/dexamethasone significantly reduced the risk of death compared with bortezomib/dexamethasone in patients with relapsed/refractory myeloma, concludes Silbermann

Rebecca Silbermann, MD, MMS, discusses current treatment options for fit patients with multiple myeloma who experience early relapse.  



Rebecca Silbermann, MD, MMS

Articles

Dr. Silbermann on the CASTOR Trial in Relapsed/Refractory Myeloma

Dr. Silbermann on the Role of Disease Biology in Multiple Myeloma

Dr. Silberman on Treatment Options in Early-Relapse Multiple Myeloma