Ravi Vij, MD, MBA, professor, Department of Medicine, Oncology Division, Section of Bone Marrow Transplantation and Leukemia, Washington University School of Medicine, medical director, Siteman Cancer Center, Barnes West County Hospital, Barnes St. Peter’s Hospital, South County Satellite, discusses the potential of cereblon E3 ligase modulators (CELMoDs) in relapsed/refractory multiple myeloma. 

Historically, immunomodulatory agents (IMiDs), such as lenalidomide (Revlimid) and pomalidomide (Pomalyst), have served as a therapeutic backbone across the paradigm of multiple myeloma, says Vij. Looking forward, it is possible that CELMoDs will become the next generation of IMiDs, Vij adds.

CELMoDs are designer molecules that attach to the cereblon molecule, which is the main target of IMiDs, Vij explains. Early efficacy data have demonstrated good response rates with CELMoDs without significant hematologic toxicity in heavily pretreated patients, Vij says. Currently, the CELMoDs iberdomide (formerly CC-220) and CC-92480 are in clinical development, concludes Vij.

Videos

Ravi Vij, MD, MBA, discusses the potential of cereblon E3 ligase modulators in relapsed/refractory multiple myeloma.  



Dr. Vij on the Potential of CELMoDs in Relapsed/Refractory Multiple Myeloma 

Ravi Vij, MD, MBA, professor of medicine, Division of Oncology, Section of Bone Marrow Transplant, Washington University School of Medicine, Siteman Cancer Center, discusses the use of maintenance and consolidation in multiple myeloma.

Post-transplant, maintenance therapy is the standard, says Vij. Most patients get lenalidomide (Revlimid) as maintenance therapy, though that may not be sufficient for high-risk patients. Patients who have deletion of 17p or other chromosome abnormalities like t(14;20) or t(14;16) may benefit from the addition of a proteasome inhibitor. Some clinicians are using dual maintenance, but there are no randomized data to suggest that it is a superior approach.

Consolidation is also being explored, though it remains experimental, explains Vij. While a the STAMINA trial failed to demonstrate a benefit in progression-free survival (PFS) with consolidative therapy, a trial done by the European Myeloma Network showed an improvement in PFS with consolidative therapy. The contradictory results may be predicated on the regimens that were used prior to transplant, says Vij. Though consolidation is not part of routine management, some investigators and treating physicians are using it in patients who do not achieve a very good partial response to deepen response post-transplant.

Dr. Vij on Maintenance and Consolidation in Newly Diagnosed Multiple Myeloma

Ravi Vij, MD, MBA, professor of medicine, Division of Oncology, Section of Bone Marrow Transplant, Washington University School of Medicine, Siteman Cancer Center, discusses the potential of quadruplets in the treatment of patients with multiple myeloma.

Vij says that the era of 4-drug treatments is imminent in myeloma. This means that the use of monoclonal antibodies as a backbone is where the field is headed. Still, Vij says that it will be some time before quadruplets best triplets in a comparative study. Adding another drug to a triplet regimen will also increase costs. However, some feel that the costs are justifiable if this is a finite therapy, Vij explains.

Currently, daratumumab (Darzalex) and elotuzumab (Empliciti) are both being explored in frontline trials, but the data are still preliminary. An interim safety analysis of daratumumab added to the triplet of lenalidomide (Revlimid) with bortezomib (Velcade) and dexamethasone was presented at the 2017 ASH Annual Meeting. These data concluded that there were no added safety signals with the addition of daratumumab to the triplet.

Ravi Vij, MD, MBA, professor of medicine, Division of Oncology, Section of Bone Marrow Transplant, Washington University School of Medicine, Siteman Cancer Center, discusses the potential of quadruplets in the treatment of patients with multiple myeloma.
 

Ravi Vij, MD, MBA

Articles

Dr. Vij on the Potential of CELMoDs in Relapsed/Refractory Multiple Myeloma

Dr. Vij on Maintenance and Consolidation in Newly Diagnosed Multiple Myeloma

Dr. Vij Discusses the Potential of Quadruplets in Myeloma