Multiple Genetic Drivers Key to Enhancing Individualized Therapy in Multiple Myeloma

New York—When treating patients with multiple myeloma, it is important to address the genetic drivers of the disease as well as it environment, as both are equally significant, Joseph Mikhael, MD, MEd, FRCPC, Professor, Translational Genomics Research Institute, Phoenix, Arizona, told attendees at the 2018 Lymphoma & Myeloma congress.

Utilizing Genomic and Genetic Information

In his opening statement, Dr Mikhael told attendees that he would be providing some insight into how they can use genomic and basic genetic information in the clinic.

Although multiple myeloma is still generally viewed as incurable, it is an area that has seen tremendous progress in recent years.

“Multiple myeloma is one of the few cancers for which we can argue that we’ve doubled—if not tripled—the average survival of patients in the last decade,” he said.

Because myeloma is a unique and challenging disease that varies significantly from patient to patient, specifically targeting the disease at its genetic basis is key.

According to Dr Mikhael, it is important to acknowledge multiple myeloma’s many driver mutations, and to understand the significant role targeted therapy plays in the treatment of this disease.
 

Attacking the Enemy and Its Environment

To illustrate the importance of targeted therapy, Dr Mikhael shared a colorful analogy with the audience.

“Imagine for a minute that the enemy (ie, myeloma) invades the building across the street. How do we get rid of that enemy?” he asked attendees.  Likening the traditional response of stem-cell transplantation to blowing up the proverbial building across the street, Dr Mikhael acknowledged that a transplant would work and be very effective, but that it would also result in a lot of unnecessary harm.

“It’s a very toxic challenge because there is a lot of collateral damage,” he said. Targeted therapy, however, can limit this excessive damage, and is developed through the use of genomic testing.

“Targeted therapy is to say, ‘Well, the enemy is on the 7th floor, so maybe we just knock out the 7th floor,’” Dr Mikhael said. 

“However, with biological therapies that we’re hearing about, we’ve come to appreciate that it’s not just about the enemy being in the building, it’s that the enemy has marshaled all the resources of that building for itself (ie, the water, electricity, Wi-Fi). So what we do now with a lot of the treatments we have, is we inhibit the enemy’s ability to control its environment, then we can inhibit the activity of that enemy,” he added, wrapping up the enemy narrative.

Every treatment modality being looked at in myeloma today (eg, CAR-T therapy, BiTE immunotherapy) helps clinicians appreciate that it is the environment myeloma inhabits that is fundamental.

Maintaining an Open Dialogue With Patients

In addition, Dr Mikhael stressed that it is crucial that clinicians maintain a good relationship with their patients.

One of the best things you can do with your patients is talk to them, he said while advising attendees to look into a favorite study of his by Basch and colleagues, the results of which emphasized the need for open communication with patients (JAMA. 2017;318[2]:197-198).

“At the end of the day, please don’t forget the importance of being able to talk to your patients,” he concluded.—Hina Khaliq