A small retrospective study conducted by Dr. Costello found that patients aged 40 and younger exhibited several high-risk features, including extramedullary plasmacytomas. These younger patients had a median overall survival of 60.7 months compared with 78.6 months for patients aged 41 and older, despite all patients receiving at least one treatment with a novel agent, 15 patients receiving high-dose therapy, and 4 patients receiving an allogeneic stem cell transplant after at least one prior autologous stem cell transplant.13
How Myeloma Affects Younger vs Older Patients
“There are differences in the retrospective data published on myeloma in younger adults,” said Dr. Costello. “When we looked at our data, we found that our patients were presenting with much more advanced disease in terms of the extent of bone disease, renal failure, and rarer findings in multiple myeloma, including extramedullary plasmacytomas and primary plasma cell leukemia, and there was a trend toward worse outcome. Ours was a small study of only about 20 patients, so I hesitate to make broad generalizations of our findings when there are larger prospective cohort studies showing better survival for younger patients.”
Dr. Costello proposed: “In trying to understand differences in outcomes, it may be that younger patients are generally healthier than older patients and may have fewer comorbidities and can tolerate more aggressive treatment, allowing for improved outcomes.
There are several large prospective observation studies underway, including Connect MM—The Multiple Myeloma Disease Registry (ClinicalTrials.gov identifier NCT01081028) and the INSIGHT MM Study (NCT02761187), which include many thousands of patients. “We will be able to pull data from subgroups of patients in these studies and, hopefully, answer many of the questions about how myeloma affects younger vs older patients and whether there are any biologic differences in the cancer in different ages,” said Dr. Costello. “One thing is clear: The average age of diagnosis in myeloma is declining. We just don’t know the reason.”
Assessing Risk Factors for Early-Onset Pancreatic Cancer
Pancreatic cancer is the third-leading cause of cancer-related death in the United States, surpassing breast cancer, and, for all stages combined, the 5-year survival rate is a dismal 9%. Although treatment options, including surgery, radiation therapy, and chemotherapy, can extend survival, the majority of patients present with advanced-stage disease, when a cure is generally not possible.
Although a diagnosis of pancreatic cancer in individuals aged 45 and younger is rare—less than 3%—the total burden of the disease on young adults compared with older adults can be significantly greater because of the number of years of potential life lost. Studies have shown that a number of risk factors might be responsible for the development of early-onset or very early–onset—defined as patients younger than age 60 and 45, respectively—pancreatic cancer. Among the top risk factors is obesity, which, according to a study by the American Cancer Society and the National Cancer Institute, accounted for an increase (on average) of 4.3% in people between the ages of 25 and 29.3 Smoking, diabetes, heavy alcohol use, family history, and BRCA1/2 gene mutations may all contribute to the development of pancreatic cancer, although there have not been large studies to determine the specific risk factors for the cancer in younger adults.
Linking Obesity to Pancreatic Cancer
“It is difficult to say for certain that obesity directly causes pancreatic cancer, but obesity and type 2 diabetes, which are on the rise in the United States, are clearly associated with an increased risk for pancreatic cancer,” said Dr. Wolpin. “We are also starting to gain a better understanding of the genetic basis of pancreatic cancer.”
At Dana-Farber, Dr. Wolpin noted that about 10% of patients who come to the clinic will have an inherited pathogenic genetic mutation, which is a higher percentage than previously realized. “These patients, on average, present with pancreatic cancer at an earlier age than people who do not have germline-associated tumors,” he said. “However, the age differential is not nearly as profound as what we see for these mutations in other cancer types, such as breast and ovarian.”
Although the percentage of younger adults diagnosed with pancreatic cancer is still modest, it is worth noting, according to Dr. Wolpin. “The incidence of pancreatic cancer is rising across all ages, including younger individuals, and, therefore, having knowledge about this disease in younger adults is important. We don’t have the depth of data on this patient population in pancreatic cancer that we do in early-onset colorectal and lung cancers, but this is an area for substantial additional research.”
DISCLOSURE: Dr. Sung reported no conflicts of interest. Dr. Boughey has received institutional research funding from Eli Lilly. Dr. Weinberg has received honoraria from OncLive, Rafael Pharmaceuticals, and Tempus; has served as a consultant or advisor to Bayer; has participated in a speakers bureau for Bayer, HalioDx, Lilly, Sirtex, and Taiho Pharmaceutical; has received institutional research funding from AbbVie, Ipsen, Isofol Medical, and Novartis; has provided expert testimony on behalf of AstraZeneca; and has been reimbursed for travel, accommodations, or other expenses by Boehringer Ingelheim and Caris Life Sciences. Dr. Oxnard is an employee of Foundation Medicine and has equity in Roche Pharmaceuticals. Dr. Costello has received research support from Celgene, Janssen, Poseida Therapeutics, and Takeda and has received honoraria for consultancy from Celgene, Takeda, Oncopeptides, and Karyopharm. Dr. Wolpin has received honoraria from Celgene and G1 Therapeutics; has served as a consultant or advisor to BioLineRx, Celgene, G1 Therapeutics, Genentech, and GRAIL; and has received research funding from Celgene and Eli Lilly.
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