Edward A. Stadtmauer, MD, section chief, Hematologic Malignancies, and Roseman, Tart, Harrow, and Shaffer Families’ President’s Distinguished Professor, University of Pennsylvania, discusses the evolving treatment landscape in multiple myeloma.

Over the past 5 years, immunotherapy has garnered significant excitement in multiple myeloma, says Stadtmauer. Traditional immunotherap​eutic agents for patients with multiple myeloma consisted of immunomodulatory agents​, such as lenalidomide (Revlimid), pomalidomide (Pomalyst), and thalidomide (Thalomid). In addition, iberdomide, a next-generation cereblon E3 ligase modulator, is currently under investigation, Stadtmauer says.

Although these agents have expanded the armamentarium, the ​addition of monoclonal antibodies, such asdaratumumab (Darzalex) and elotuzumab (Empliciti), have transformed the up-front and relapsed/refractory treatment paradigms for patients with multiple myeloma, Stadtmauer concludes.

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Edward A. Stadtmauer, MD, discusses the evolving treatment landscape in multiple myeloma.

Dr. Stadtmauer on the Evolving Treatment Landscape in Multiple Myeloma 

Edward A. Stadtmauer, MD, section chief, Hematologic Malignancies, and Roseman, Tart, Harrow, and Shaffer Families’ President’s Distinguished Professor, University of Pennsylvania, discusses what makes BCMA a unique target in multiple myeloma.

Similar to CD19-targeting in lymphoma, BCMA-targeting prevents on-target, off-tumor toxicity, explains Stadtmauer. Most tissue in the body does not express BCMA, continues Stadtmauer. However, mature lymphoid cells such as plasma cells do, which creates an actionable target.

As such, success in targeting BCMA in multiple myeloma has been noted through CAR T-cell therapy and other immunotherapeutic agents that arecurrently in development.

Edward A. Stadtmauer, MD, discusses what makes BCMA a unique target in multiple myeloma. 
 

Dr. Stadtmauer on BCMA-Targeting in Multiple Myeloma

Edward A. Stadtmauer, MD, section chief, Hematologic Malignancies, and Roseman, Tart, Harrow, and Shaffer Families’ President’s Distinguished Professor, Penn Medicine, University of Pennsylvania, discusses promising targets in multiple myeloma.

BCMA has been shown to be a novel target in multiple myeloma because it is expressed on the majority of myeloma cells. CD38 has also proven to be a valuable target in myeloma, having led to the development of the monoclonal antibodies daratumumab (Darzalex) and isatuximab. Now, CD38-targeted CAR T-cell therapy and CD38-targeted bispecific T-cell engagers are also under investigation, says Stadtmauer.

In terms of lesser established targets, CS1 and therein SLAMF7, as well as NY-ESO-1 are also under evaluation. NY-ESO-1 is a member of the cancer-testis antigen family of proteins, and may prove to be a viable immunotherapy target for vaccines and adoptive T-cell therapies, concludes Stadtmauer.

Dr. Stadtmauer Discusses Promising Targets in Multiple Myeloma

Edward A. Stadtmauer, MD, section chief, Hematologic Malignancies, Abramson Cancer Center, University of Pennsylvania, discusses the use of selinexor (Xpovio) in patients with heavily pretreated, relapsed/refractory multiple myeloma. 

The agent was approved based on data from the phase II STORM trial which showed an objective response rate of 25.3% in 83 patients. According to Stadtmauer, selinexor has a novel mechanism of action that attributes to its marked activity. 

However, the drug does have toxicities. In parts 1 and 2 of the trial, the most common adverse events (≥20%) were thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

The benefit of selinexor should not be overshadowed by its side effects, Stadtmauer says. However, with proper management strategies, these side effects can be treated appropriately. 

Pending future study, selinexor is likely to be used in lower doses in combination rather than in higher doses as a single agent, says Stadtmauer.

Edward A. Stadtmauer, MD, discusses the use of selinexor in patients with heavily pretreated, relapsed/refractory multiple myeloma. 
 

Dr. Stadtmauer on Utility of Selinexor in Multiple Myeloma 

Edward A. Stadtmauer, MD, section chief of Hematologic Malignancies, Abramson Cancer Center, University of Pennsylvania, discusses the current challenges with multiple myeloma.

The biggest challenge with multiple myeloma is understanding which combinations or sequences to use with these field-changing agents, explains Stadtmauer.

Ongoing trials are helping oncologists understand more about when and how long to treat patients with these agents. Stadtmauer says he is hopeful about the outcome for patients with multiple myeloma.

Edward A. Stadtmauer, MD

Articles

Dr. Stadtmauer on the Evolving Treatment Landscape in Multiple Myeloma

Dr. Stadtmauer on BCMA-Targeting in Multiple Myeloma

Dr. Stadtmauer Discusses Promising Targets in Multiple Myeloma

Dr. Stadtmauer on Utility of Selinexor in Multiple Myeloma

Dr. Stadtmauer on Current Challenges With Multiple Myeloma