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 integration of selinexor (Xpovio) into the relapsed/refractory multiple myeloma armamentarium.

Selinexor, an XPO1 inhibitor, has demonstrated utility in patients with triple-class refractory multiple myeloma, says Vij. The agent was first approved in June 2019 for use in combination with dexamethasone in patients with relapsed/refractory disease who have received 4 or more prior therapies and whose disease is refractory to 2 or more proteasome inhibitors, 2 or more immunomodulatory agents, and a CD38-directed monoclonal antibody.

However, findings from the phase 3 BOSTON trial led to the December 2020 FDA approval of selinexor in combination with bortezomib (Velcade) and dexamethasone for patients with multiple myeloma who have received at least 1 prior therapy. Notably, this once-weekly regimen appears to confer greater efficacy and less neuropathy vs twice-weekly bortezomib and dexamethasone alone, says Vij.

Additionally, since the integration of the agent into the multiple myeloma armamentarium, the field has become more comfortable with managing selinexor-related toxicities, says Vij. Patients receiving selinexor may require antiemetic agents, appetite stimulants, and antidiarrheal agents to manage toxicities, says Vij. Dose monitoring, intravenous fluids, and growth factor support may be required in heavily pretreated patients, concludes Vij. 

Videos

Ravi Vij, MD, MBA, discusses the integration of selinexor into the relapsed/refractory multiple myeloma armamentarium.  



Dr. Vij on the Integration of Selinexor in Relapsed/Refractory Multiple Myeloma 

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.

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 optimal induction therapy in the treatment of patients with multiple myeloma.

Transplant remains the standard of care in eligible patients, says Vij, as it is known to demonstrate a superior progression-free survival. The optimal induction regimen is unknown, explains Vij, though most physicians will use bortezomib (Velcade), lenalidomide (Revlimid), and dexamethasone (VRd).

In the frontline setting, carfilzomib (Kyprolis) is being examined as a potential substitute for bortezomib—in some cases, it is already being implemented into practice. The use of carfilzomib is being driven by studies that have demonstrated a superior depth of response compared with what has been seen historically. Physicians are eagerly awaiting the randomized study comparing frontline carfilzomib, lenalidomide, and dexamethasone with VRd, says Vij, which will help determine the optimal induction regimen.

Dr. Vij on the Optimal Induction Therapy in Multiple Myeloma

Ravi Vij, MD, associate professor, medicine, Division of Oncology, Section of Bone Marrow Transplant, Siteman Cancer Center, discusses the institution's tumor banking initiative for next-generation sequencing in multiple myeloma.

Initially, the tumor banking initiative at Siteman Cancer Center was set up to research acute myeloid leukemia and myelodysplastic syndrome, Vij says. The tumor tissues were eventually used for next-generation sequencing, which has helped with the genomics of these diseases to help develop targeted therapies.

The tumor bank is being pulled from again, Vij explains, to research next-generation sequencing in multiple myeloma. Coupled with new technologies, it will help to better define the mutational spectrum of patients with multiple myeloma. These tissues are also to be used in collaboration with other institutions and companies to help improve outcomes of these patients.

Additional tumor bank initiatives are taking place at other institutions for other malignancies, Vij says. 

Ravi Vij, MD

Articles

Dr. Vij on the Integration of Selinexor in Relapsed/Refractory Multiple Myeloma

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

Dr. Vij on the Optimal Induction Therapy in Multiple Myeloma

Dr. Vij on Tumor Bank for Multiple Myeloma at Siteman Cancer Center