By Mark L. Fuerst
Older multiple myeloma patients can safely undergo transplant and achieve similar clinical benefits as younger patients, according to a new study (Abstract 782). The results also show that a standard dose of melphalan may be given safely to an older population, suggesting that more patients could benefit from transplant than typically are offered it.
"Autologous hematopoietic cell transplantation (AHCT) is an effective treatment to achieve deep and durable remission in multiple myeloma. Less than 50 percent of all myeloma patients get AHCT. Race or ethnic disparities exist in myeloma for receipt of AHCT," said senior author Anita D'Souza, MD, of the Medical College of Wisconsin, at a press briefing at the 2019 ASH Annual Meeting.
Typically, transplantation is offered to patients under 70 years of age, although the median age of diagnosis of multiple myeloma is 70 years. Older patients are often excluded from clinical trials studying transplant because they tend to have a greater number of health issues.
Without trials proving newer, aggressive treatments are safe for older patients, doctors may avoid them on the assumption that they are too risky. When they are included in trials, older patients often receive a reduced dose of the conditioning chemotherapy drug melphalan.
"This study shows that you can perform these transplants safely in older patients, and the older patients get the same benefits from these treatments as the younger patients do," said D'Souza. "In addition, if there are no contraindications other than simply age, it's worth trying the higher dose of melphalan. Age alone should not be a reason to automatically reduce the dose."
The study also strengthens the argument that multiple myeloma patients should not be excluded from clinical trials based on age alone, said D'Souza. She noted that half of multiple myeloma patients are age 70 or older at the time of diagnosis.
Using the Center for International Blood and Marrow Transplant Research database, the researchers examined health records of approximately 16,000 patients who received AHCT with melphalan in the U.S. between 2013 and 2017. All age groups had similar distribution of gender, race, ethnicity, Karnofsky Performance score, comorbidity index (HCT-CI), stage III by Durie-Salmon/International Staging System. There was a higher proportion of high-risk cytogenetics in patients age 70 and older (30%), compared to those ages 40-49 years (24%) and 20-39 years (20%) in this population. Older patients were more likely to be white compared to younger patients.
After adjusting for factors such as functional status, comorbidities, and disease stage, the researchers found patients who received their treatments at age 70 or older had similar rates of relapse or disease progression, progression-free survival (PFS), and death not caused by a cancer relapse as those ages 60-69 years.
Of patients age 70 and older, about 40 percent received the full dose of melphalan 200 mg/m2 and 60 percent received a reduced dose of 140 mg/m2. Those receiving the reduced dose had significantly worse outcomes and lower survival rates. Among the older cohort, "melphalan dose was a surrogate for worse outcomes including non-relapse mortality at 100 days, PFS at 2 years, and overall survival at 2 years," said D'Souza. She noted that it is impossible to determine whether worse outcomes in the lower dose melphalan group may be due to higher frailty and comorbidities in this cohort of patients.
Specialists often support the use of AHCT in otherwise healthy older patients, D'Souza said. Oncologists in community hospitals, where many patients are first treated, often fail to refer older patients to transplant centers. The researchers noted a significant increase in the proportion of older patients receiving AHCT in 2017 compared to 2013, suggesting that referrals to AHCT specialists increased over time.
In addition to age disparities, the study also speaks to important racial disparities in myeloma care. Myeloma is twice as common in African Americans as whites, yet transplantation rates are significantly lower among black patients. Age likely adds to the barriers for these patients, D'Souza said.
The researchers noted that this is the largest study of AHCT in older adults with multiple myeloma. They concluded that, "while our data may highlight referral and access biases regarding which older patients may be referred for ASCT, our results confirm that patients 70 years and older can undergo transplant safely and achieve similar benefits as 60- to 69-year-old patients. Our results also suggest that melphalan 200 mg/m2 may be given safely in the 70 and older population."
They suggest their analysis "confirms that AHCT has similar benefits in terms of disease control (relapse and PFS) in both young and older multiple myeloma patients. This benefit is seen even in a contemporaneous era where proteasome inhibitors and/or immunomodulator drugs are used in upfront treatment. Thus, AHCT remains a safe consolidation therapy across all age groups of multiple myeloma patients."
In conclusion, D'Souza said: "More multiple myeloma patients age 70 years and older are undergoing AHCT in the U.S. over time. Our data highlight referral and access biases regarding which older patients may be referred for transplant. Patients age 70 years and older can undergo AHCT safely and achieve similar anti-myeloma benefits to younger patients. AHCT remains a safe consolidation treatment option across all age groups of multiple myeloma patients."
Mark L. Fuerst is a contributing writer.