A recent report published by a group of multiple myeloma experts in Europe recommends individualized treatment strategies for elderly myeloma patients based on their physical health.

Specifically, the authors suggest that physicians evaluate the age and physical condition of elderly myeloma patients prior to therapy in order to create well-tolerated regimens that would optimize treatment outcomes.

According to Dr. Antonio Palumbo, from the University of Torino in Italy and the lead author of the report, tailored therapies are important for elderly myeloma patients because these patients often cannot tolerate the same treatments used for younger patients.

“For patients older than 75 years, or for elderly patients with [concurrent illnesses], a gentler approach with reduced doses is needed. In case these patients experience a serious side effect with reduced-dose regimens, further reductions are necessary,” Dr. Palumbo told The Myeloma Beacon.

“This strategy is essential to maintain patients on therapy and hence allow them to benefit from the treatment,” he added.

Although adults of any age can be diagnosed with multiple myeloma, the majority of myeloma patients are over 65 years of age, and a third are over 75 years.

While autologous stem cell transplantation is the standard treatment for myeloma patients under 65 years of age, most elderly patients are unable to tolerate this procedure because of poor physical health and concurrent illnesses. Instead, elderly patients have traditionally received melphalan (Alkeran) plus prednisone, a combination that is generally well-tolerated in this population.

In recent years, novel drugs such as Revlimid (lenalidomide), thalidomide (Thalomid), and Velcade (bortezomib) have improved the overall survival of myeloma patients under 60 years of age. However, patients between 60 and 69 years of age have not experienced as much of an increase in their overall survival, and patients over 70 years of age have experienced no increase in survival with novel drugs.

According to the authors of the report, elderly patients are more likely than younger patients to experience severe treatment-related side effects because of their declining physical condition. Past studies, for instance, have shown that between 42 percent and 53 percent of elderly myeloma patients experience a severe side effect in the early stages of treatment with a novel drug.

“Elderly myeloma patients are more susceptible to side effects [of treatment], have a lower tolerability for full drug doses, and [because of concurrent illnesses] may be on other medications that interact with their myeloma treatment,” explained Dr. Parameswaran Hari of the Medical College of Wisconsin in Milwaukee, who was not involved with the study.

Due to treatment-related side effects, physicians often stop treatment of elderly patients prematurely or lower drug doses, thereby compromising treatment efficacy. According to Dr. Palumbo, treatment of approximately 40 percent of elderly myeloma patients is discontinued because of treatment-related problems.

As a result, elderly patients have a significantly shorter survival time than younger patients. Results of a large study conducted in 2008, for instance, show that myeloma patients over 50 years of age had a median survival time of 3.7 years compared to 5.2 years for patients under 50 years of age.

In their report, the myeloma experts recommended that physicians assess the overall physical condition and organ function of elderly myeloma patients prior to beginning therapy in order to determine their ability to tolerate certain regimens.

Specifically, they recommended that patients be evaluated for frailty, disabilities, and concurrent illnesses, along with peripheral neuropathy (a condition characterized by burning, tingling, or numbness in the hands and feet), and heart, liver, and kidney function. They believed that these evaluations would enable physicians to select well-tolerated regimens and optimize treatment efficacy for these patients.

The authors proposed a different treatment plan for each patient after he or she is evaluated for the risks of experiencing treatment-related complications. Dr. Palumbo said that this strategy would reduce the need to stop treatments prematurely for elderly myeloma patients.

Based on this strategy, patients with at least one risk factor—including age above 75 years, frailty, disabilities, concurrent illnesses, or a severe non-blood-related side effect from myeloma therapy—should be considered for a reduced-dose treatment plan. Moreover, patients with at least one risk factor who experience a severe non-blood-related side effect should start treatment with even lower doses.

The authors also suggested that elderly patients who develop severe side effects during treatment should stop therapy and continue with reduced doses once their side effects have disappeared. In addition, those who do not respond after three cycles of therapy should start on a different regimen.

The authors cautioned against giving therapies to elderly patients with relapsed or refractory myeloma that may aggravate any pre-existing conditions or increase the side effects caused by previous therapies.

Furthermore, they recommended supportive therapy for elderly patients in order to improve their ability to tolerate treatment.

They suggested the use of granulocyte colony-stimulating factors to prevent low white blood cell counts and the use of erythropoietin therapy (drugs that stimulate the bone marrow to produce red blood cells) for the treatment of anemia (low red blood cell counts).  To prevent blood clots caused by Revlimid or thalidomide, they recommended either aspirin or low-molecular-weight heparins.

They also suggested local pain medication and radiotherapy for the treatment of bone pain and bisphosphonates (drugs that slow the breakdown of bone) to reduce the risk for bone fractures.

Dr. Hari agreed that this framework would help community physicians to better tailor therapies for elderly myeloma patients. However, he commented that the guidelines should also include stem cell transplantation as a viable option for some elderly patients.

“I would also recommend that patients be evaluated for [stem cell] transplants in these guidelines. Transplants should not be out of reach for patients based only on age if they are in good physical shape,” Dr. Hari told The Myeloma Beacon.

The authors added that further studies are needed to better define the role of certain risk factors such as age, concurrent illnesses, and frailty in elderly patients.  They suggested that data from these follow-up studies would eventually lead to tailored therapies and, therefore, improve the overall survival of elderly myeloma patients.

“Future studies need to be more focused on frail patients older than 75 years who have [concurrent illnesses]. Indeed, elderly patients (older than 65 years) represent the majority of multiple myeloma patients, and the very elderly (older than 75 years) are currently underrepresented in clinical trials,” said Dr. Palumbo.

Dr. Hari agreed that elderly myeloma patients should receive more opportunities to participate in future clinical trials.

“Clinical trials [in the U.S.] usually have strict exclusion criteria [and are often] designed for younger, healthy patients,” said Dr. Hari. “[We should] promote the enrollment of elderly patients into these trials and relax standard eligibility criteria.”

For more information, please see the report in the journal Blood (abstract) and the Beacon series on managing side effects in older patients.