Jason Valent, MD, an oncologist at Cleveland Clinic, discusses ongoing research with immunotherapy, specifically checkpoint inhibitors, in the treatment of patients with multiple myeloma.

Although trials with checkpoint inhibitors were halted in 2017 due to safety concerns, some trials since reopened, says Valent. The accrual for a study examining the use of atezolizumab (Tecentriq) in combination with daratumumab (Darzalex) and pomalidomide (Pomalyst) (NCT02431208) slowed when trials with immunotherapy were halted, but the study has since reopened and is planned to move forward.

The efficacy of checkpoint inhibitors in multiple myeloma has yet to be fully understood, explains Valent. However, there is a strong rationale for combining these agents with daratumumab. If some of the immune protection provided to the malignant cell can be eliminated with a checkpoint inhibitor, a drug like daratumumab may be better able to stimulate the immune system and induce greater responses, explains Valent.

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Dr. Valent on Ongoing Research With Immunotherapy in Multiple Myeloma

Jason Valent, MD, an oncologist at Cleveland Clinic, discusses the recent FDA approval to expand prescribing information to include a once-weekly dosing option for carfilzomib (Kyprolis) to use in combination with dexamethasone for the treatment of patients with relapsed/refractory myeloma.

The FDA based their decision on results from the phase III ARROW study, which demonstrated that carfilzomib administered once weekly at 70 mg/m

 with dexamethasone resulted in a prolonged progression-free survival (PFS) compared with the standard twice-a-week treatment. Median PFS was 11.2 months with the once-weekly schedule versus 7.6 months with the twice-weekly regimen.

The biggest advantage of this new dosing regimen is that it is more convenient for patients, Valent says. Instead of going to the clinic twice-a-week on consecutive days, patients now only have to go once. Valent adds that the new regimen may also reduce the toxicities associated with carfilzomib, despite the higher dose.

Jason Valent, MD, an oncologist at Cleveland Clinic, discusses the recent FDA approval of dose-adjusted carfilzomib in patients with myeloma.

Dr. Valent on Dose-Adjusted Carfilzomib in Myeloma

Jason Valent, MD, oncologist, Cleveland Clinic, discusses the potential application of minimal residual disease (MRD) negativity in patients with multiple myeloma.

Though MRD negativity is prognostic and not yet predictive in multiple myeloma, Valent says there is still a story to be told regarding its application in myeloma. On October 2, the FDA approved the next-generation sequencing assay clonoSEQ as a test for MRD in patients with acute lymphoblastic leukemia or multiple myeloma. The sequencing assays seem to provide an early signal for overall survival (OS), says Valent. If the FDA accepts MRD negativity as a surrogate for OS advantage, that would increase the use of MRD testing, especially in clinical trials, notes Valent.

There are also potential roles for the technology in the everyday patient setting, though it would require sequential bone marrow sampling over time. If repeat bone marrow sampling is done in patients who are in a complete response, physicians may be better able to determine when they are going to come out of that complete response and alter treatment accordingly, explains Valent.

Jason Valent, MD

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Dr. Valent on Ongoing Research With Immunotherapy in Multiple Myeloma

Dr. Valent on Dose-Adjusted Carfilzomib in Myeloma

Dr. Valent on MRD Negativity in Multiple Myeloma