Saad Z. Usmani, MD, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, discusses chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma.

CAR T-cell therapies have been making their way through the field of multiple myeloma. Studies presented at the 2017 ASCO Annual Meeting showed that when targeting BCMA, CAR T-cell technology appeared to be tolerable and efficacious, Usmani says.

Larger cohorts are needed though, Usmani adds, as investigators still must indicate which patients will benefit from this therapy.

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Saad Z. Usmani, MD, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, discusses CAR T-cell therapy in multiple myeloma.

Dr. Usmani Discusses CAR T-Cell Therapy in Multiple Myeloma

Saad Z. Usmani, MD, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, discusses combining daratumumab (Darzalex) for patients with multiple myeloma.

Depending on the therapy that patients have received for their first-line of treatment, daratumumab may have the ability to be paired with other agents, explains Usmani.

A concern that physicians have is long-term effects of daratumumab on the immune system. As of now, there is no clinically significant concerns but it is something we will continue to watch, states Usmani.

Dr. Usmani on Combining Daratumumab for Multiple Myeloma

Saad Z. Usmani, MD, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, discusses the mechanisms of daratumumab (Darzalex) as well as the reported response rates in combination with other agents in multiple myeloma.

Daratumumab can impact the NK and T-cell receptors, although one of the mechanisms in which it is effective is to have an expansion of CD8-positive T cells that appear to be clonal in some studies, Usmani explains. However, there are limited data to see what the effects of these immunologic changes will be in the long run.

With the triplet regimen of daratumumab, lenalidomide (Revlimid), and dexamethasone, Usmani adds that there are unprecedented depths of response. Additionally, there are patients who have achieved minimal-residual disease (MRD) negativity, including those in the relapse setting. While it depends on which MRD-negativity cutoff clinicians use, there are patients reaching this stage that was not previously commonly seen in practice, he says.

Dr. Usmani on Mechanisms and Response Rates With Daratumumab in Myeloma

Saad Z. Usmani, MD, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, discusses administering daratumumab (Darzalex) in patients with relapsed or refractory multiple myeloma.

This was an open-label, multicenter, dose-escalation phase Ib study to assess the subcutaneous delivery of daratumumab.

Intravenous infusion of daratumumab can take up to 8 hours, which is an inconvenience for many patients. In this study, subcutaneous delivery was tested as an attempt to cut down time spent administering the therapy.

Both the 1200 mg and 800 mg fixed doses were found to be tolerable, Usmani explains.

Dr. Usmani on Subcutaneous Delivery of Daratumumab in Myeloma

Saad Z. Usmani, MD, Department of Hematologic Oncology and Blood Disorders, Levine Cancer Institute/Carolinas HealthCare System, discusses the importance of the CASTOR and POLLUX trials for the treatment of patients with multiple myeloma.

The CASTOR and POLLUX trials are likely among the most exciting trials in the field of multiple myeloma, Usmani explains. As a result of those 2 trials, daratumumab (Darzalex) was approved by the FDA for relapsed patients with myeloma. The phase III POLLUX and CASTOR studies explored the addition of daratumumab to lenalidomide (Revlimid) and dexamethasone or bortezomib (Velcade) and dexamethasone, respectively.

Findings from both trials demonstrated that daratumumab can be combined with either an immunomodulatory agent or an proteasome inhibitor in the relapsed setting, and that the addition of daratumumab is superior than either of the 2 drugs alone.

Dr. Usmani on Importance of CASTOR/POLLUX Trials in Myeloma

Saad Z. Usmani, MD, hematology and medical oncology, Levine Cancer Institute, Carolinas HealthCare System, discusses results of a phase Ib/II study examining the combination of ibrutinib plus carfilzomib in patients with relapsed/refractory multiple myeloma.

Patients who were eligible to receive the combination were pretreated with bortezomib and an immunomodulatory agent, Usmani explains. The median prior lines of therapy was three; 25% of patients had previous exposure to carfilzomib and pomalidomide.

The highest dose of ibrutinib administered to patients was 560 mg, while the highest dose of carfilzomib was 227 mg. In the combination arm, the overall response rate was approximately 58% and the clinical benefit rate was 67%. No significant toxicities were seen with the combination, Usmani adds. Next steps include a dose expansion as well as a phase III study.

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Saad Z. Usmani, MD, hematology and medical oncology, Levine Cancer Institute, Carolinas HealthCare System, discusses results of a phase Ib/II study examining the combination of ibrutinib plus carfilzomib in patients with relapsed/refractory multiple myeloma. 


Dr. Usmani on Ibrutinib/Carfilzomib in Patients With Multiple Myeloma

Saad Z. Usmani, MD, director, Clinical Research Hematologic Malignancies, director, Plasma Cell Disorders, Levine Cancer Institute/Carolinas Healthcare System, discusses daratumumab for patients with relapsed/refractory multiple myeloma.

Daratumumab monotherapy is being investigated as part of the ongoing phase II MMY2002 study. Results from the study, presented at the 2015 ASCO Annual Meeting, demonstrated a 65% 1-year overall survival rate and a 29.2% objective response rate in patients with double refractory heavily pretreated multiple myeloma..

The study has given community oncologists an effective monoclonal antibody for multiple myeloma that can be safely used for patients that have not had success with approved drugs, says Usmani. .

Because the drug has a positive safety profile, it is a good candidate for pairing with other therapies. Daratumumab combinations are currently being investigated to determine if responses and outcomes for patients with myeloma can be improved without adding the burden of additional side effects, says Usmani. .

Saad Z. Usmani, MD

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