EHA: Treating Newly Diagnosed Frail Myeloma Patients

How do myeloma experts handle frail patients? 

Alessandra Lorocca, MD, PhD of the City of Health and Science University Hospital in Turin, Italy shared her experience and the very latest in newly diagnosed myeloma at the European Hematology Association (EHA) meeting in Frankfurt, Germany.

Causes of Frailty

Dr. Lorocca said that frailty can be driven by age-related biological changes like older age, other diseases like heart or lung conditions or other geriatric issues.

She also said that frailty can be caused by the disease itself. For example, when patients are newly diagnosed the myeloma itself may have made them frail by damaging their spine or kidneys, but once they receive treatment, they are no longer considered frail. 

Myeloma is typically diagnosed in an older population with 35.5% of myeloma patients being over 65, 31.9% of patients being diagnosed between 65-74 and 32.6% of patients being over 75. 

There is a frailty score created by the International Myeloma Working Group (IMWG) that divides patients into frail, fit or intermediate fit categories. Based on trials that used the IMWG frailty criteria, frail patients had worse outcomes compared to fit or intermediate-fit patients. 

However, she mentioned that the IMWG frailty score has limitations. A new, simplified score was used in the FIRST clinical trial that included age, the Eastern Cooperative Oncology Group performance status number and co-conditions (kidney issues, heart conditions, diabetes, etc) that a patient might have. 

Treating Frail Patients

Revlimid and dex are the "traditional" standard of care treatment for newly diagnosed frail patients who are not able to receive a stem cell transplant. 

But in the MAIA trial that added daratumumab to Relimid and dex, patients had better outcomes and better quality of life.

Another study called the ALCYONE study combined daratumumab with Velcade, melphalan and prednisone (a combination more frequently used outside of the United States) and patients also had good outcomes. 

However, frail patients in both of these trials had higher side effects like low blood counts and infections. She said that removing dexamethasone can help. 

Other open clinical trials are now testing a new class of treatment called cell mods (iberdomide) with daratumumab vs. iberdomide and dex. An additional study called the MajesTEC-7 study is testing the bispecific antibody teclistamab with daratumumab and Revlimid vs. daratumumab, Revlimid and dexamethasone. 

Managing Side Effects

Many frial patients can't join clinical trials because the criteria to join excludes them. Dr. Lorocca suggests that doctors use frailty scores and allow for dose modifications. 

In her practice she reduces doses, ensures her patients are up-to-date on their vaccines (like the shingles vaccine and keeps her patients reactivated with the Hepatitis vaccine). 

What the Future Holds

Dr. Lorocca closed with a few suggestions: 

• Prove the usefulness of the IMWG frailty score, or use a different and better score
• Determine the best therapy for frail patients based on the outcomes of the clinical trials
• Watch to see how the BCMA therapies work for frail patients - they are effective but safety could be an issues