Joseph Mikhael, MD, professor, Applied Cancer Research and Drug Discovery Division, Translational Genomics Research Institute, affiliate, City of Hope Cancer Center, chief medical officer, International Myeloma Foundation, discusses the promise of bispecific antibodies in multiple myeloma.

Novel therapeutic choices are always needed in multiple myeloma because patients may be ineligible for certain treatments for various reasons, such as renal insufficiency or comorbidities, Mikhael says. 

Bispecific antibodies are a promising emerging therapeutic class in multiple myeloma. These agents could offer an off-the-shelf T-cell therapy for patients who can’t or don’t want to wait for CAR T-cell therapy manufacturing, Mikhael says. Additionally, bispecific antibodies that engage natural killer cells could emerge with similar efficacy but less risk of cytokine release syndrome vs T-cell therapies.

Finally, bispecific antibodies could have a role as maintenance therapy for patients who obtain a response with CAR T-cell therapy, Mikhael says. As has always been a goal of research in multiple myeloma, the field is continuing to improve treatment by synergizing the activity of different agents, such as CAR T-cell therapy and bispecific antibodies, Mikhael concludes.

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Joseph Mikhael, MD, discusses the promise of bispecific antibodies in multiple myeloma. 



Dr. Mikhael on the Promise of Bispecific Antibodies in Multiple Myeloma 

Joseph Mikhael, MD, professor in the Applied Cancer Research and Drug Discovery Division, Translational Genomics Research Institute, affiliate, City of Hope Cancer Center, chief medical officer, International Myeloma Foundation, discusses treatment selection for early relapse in multiple myeloma.

Treatment selection is challenging in patients with multiple myeloma who relapse early and should be adapted to each individual patient, Mikhael says. Notably, a wealth of options are available that can be tailored based on patient-related, disease-related, and therapy-related factors, Mikhael says. 

For example, physician or patient preference may dictate whether a patient should receive oral vs intravenous treatment, Mikhael says. Factors relating to comorbidities or prior toxicities could also inform optimal treatment selection, Mikhael explains. Additionally, disease risk could indicate that one regimen may be superior to another in a particular patient, Mikhael says. Ultimately, these factors must be weighed together to determine which therapeutic option could provide a patient with the deepest and most durable response early on, Mikhael says.

Additionally, key principles of relapse can be used in conjunction with these factors to guide treatment selection. For example, most treatments in the early relapse setting do not feature drugs that a patient has already progressed on, Mikhael says. As such, treatment typically consists of a combination regimen that introduces a new mechanism of action to target the myeloma, Mikhael concludes. 

Joseph Mikhael, MD, discusses treatment selection for early relapse in multiple myeloma.  



Dr. Mikhael on Treatment Selection for Early Relapse in Multiple Myeloma 

Joseph Mikhael, MD, a professor in the Applied Cancer Research and Drug Discovery Division at the Translational Genomics Research Institute, an affiliate of City of Hope Cancer Center, and chief medical officer of the International Myeloma Foundation, discusses novel agents used to treat patients with multiple myeloma.

The field of multiple myeloma has undergone many changes over the past few years. Two new classes of drugs have emerged in the treatment arsenal: nuclear export inhibitors such as selinexor (Xpovio) and BCMA-targeted antibody-drug conjugates such as belantamab mafodotin-blmf (Blenrep), says Mikhael.

Multiple myeloma is a disease in which most patients are not achieving cure, adds Mikhael. Almost all patients will become refractory to the main 5 agents that are currently being used to treat this disease: bortezomib (Velcade), lenalidomide (Revlimid), pomalidomide, carfilzomib (Kyprolis), and daratumumab (Kyprolis), Mikhael concludes.

Joseph Mikhael, MD, discusses novel agents used to treat patients with multiple myeloma.

Dr. Mikhael on the Advances Made in Multiple Myeloma Treatment

Joseph Mikhael, MD, professor, Applied Cancer Research and Drug Discovery Division, Translational Genomics Research Institute (TGen), an affiliate of City of Hope Cancer Center, chief medical officer, International Myeloma Foundation, discusses remaining challenges in high-risk multiple myeloma.

Within the past decade, the average survival of patients with multiple myeloma has significantly improved compared with historic rates, says Mikhael. However, survival has not been improved to the same degree in patients with high-risk disease.

Additionally, patients with extramedullary disease, who can also be considered high risk, remain a challenging patient population to treat, Mikhael explains. Extramedullary disease presents 

 outside of the medullary space. Moreover, these patients can be challenging to image, measure, and treat as they may have heavy disease burden. Future research efforts should aim to identify a treatment strategy for patients with extramedullary disease, concludes Mikhael. 

Joseph Mikhael, MD, discusses remaining challenges in high-risk multiple myeloma.  



Dr. Mikhael on Remaining Challenges in High-Risk Multiple Myeloma

Joseph Mikhael, MD, professor, Applied Cancer Research and Drug Discovery Division, Translational Genomics Research Institute (TGen), an affiliate of City of Hope Cancer Center, chief medical officer, International Myeloma Foundation, discusses unmet needs in triple-class refractory multiple myeloma. 

Within the past year, the multiple myeloma armamentarium has expanded to include the novel XPO1 inhibitor selinexor (Xpovio) and the BCMA-directed antibody-drug conjugate belantamab mafodotin-blmf (Blenrep) for patients with heavily pretreated, relapsed/refractory disease. Additionally, the CD38-directed antibody isatuximab-irfc (Sarclisa) was also approved in combination with pomalidomide (Pomalyst) and dexamethasone for patients with relapsed/refractory multiple myeloma who have progressed on 2 or more prior therapies, including lenalidomide (Revlimid) and a proteasome inhibitor. 

However, despite a multitude of available agents, myeloma remains incurable, Mikhael says. The majority of patients will become triple-class refractory and progress on bortezomib (Velcade), lenalidomide, pomalidomide, carfilzomib (Cabometyx), and daratumumab (Darzalex). 

Treatment selection with these novel agents should be individualized for patients with triple-class refractory disease, Mikhael says. Additionally, future research efforts should aim to evaluate these therapies in combinations and earlier on in the treatment course.

Joseph Mikhael, MD, discusses unmet needs in triple-class refractory multiple myeloma.  


Joseph Mikhael, MD

Articles

Dr. Mikhael on the Promise of Bispecific Antibodies in Multiple Myeloma

Dr. Mikhael on Treatment Selection for Early Relapse in Multiple Myeloma

Dr. Mikhael on the Advances Made in Multiple Myeloma Treatment

Dr. Mikhael on Remaining Challenges in High-Risk Multiple Myeloma

Dr. Mikhael on Unmet Needs in Triple-Class Refractory Multiple Myeloma