As a Geriatric Hematologist, attending the American Society of Hematology (ASH) Annual Meeting was exciting for me because I was able to witness firsthand the cutting edge of research focusing on improving outcomes in older adults with hematologic malignancies. Here, I will highlight a few relevant studies in older adults with acute myeloid leukemia (AML) as well as two studies that I had the honor to present.
More than half of new AML cases are diagnosed in older adults. Treatment can be challenging in this population as older adults do not tolerate intensive chemotherapy as well as younger adults. Lower intensity treatments are available but are usually palliative. Therefore, investigators are actively looking for regimens that are more efficacious and better tolerated by older adults with AML. Venetoclax, a BCL-2 inhibitor, was approved by the FDA just two weeks before ASH to be used in combination with hypomethylating agents or low-dose cytarabine in those who are unfit for induction chemotherapy, the majority of whom are older adults. Maiti et al. presented an interim analysis of a phase two study evaluating venetoclax and decitabine in 48 patients with AML and high-risk myelodysplastic syndrome; 24 patients aged >60 years with newly diagnosed AML were included. Although the sample size was small, the complete response (CR)/complete response with incomplete count recovery (CRi) rate was 91% in this group of patients and there were no early deaths. The high response rate is remarkable, though we must be mindful of the small sample size and patient selection bias. Hopefully, this will encourage future randomized controlled trials comparing intensive chemotherapy against venetoclax and decitabine. Head-to-head trials comparing intensive and lower intensity treatments have been challenging to conduct due to higher treatment-related toxicity of the former and perceived lower efficacy of the latter. With these data, I am hopeful that we are seeing the dawn of a new treatment option for older adults with AML that will help them to live longer and with a better quality of life.
Another interesting abstract by the East German Study Group looked at individualized response-based approach in 109 patients aged >60 years with newly diagnosed AML. Patients were initially treated with azacitidine for seven days. Those who had blasts ≥45% on day 15 received intensive chemotherapy (mitoxantrone and cytarabine), and those with blasts <45% continued to receive azacitidine on day 28. On day 56, those who were in CR/CRi received azacitidine or allogeneic stem cell transplant, and others received intensive chemotherapy followed by azacitidine maintenance or allogeneic HCT if remission was achieved on day 90. With this approach, 24/109 patients did not receive intensive chemotherapy. The response rate was 64% and the two-year overall survival (OS) was 32%. Although this approach needs to be tested further, it introduces the concept of response-adapted therapy in older adults and potentially avoids the need for intensive treatment.
Over- and under-treatment (the latter in particular) of older adults with AML has been my research interest. Prior research suggests that <40% of older adults with AML receive leukemia-directed therapy despite several investigators having shown that treatment improves outcomes. Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database, Medeiros et al. demonstrated that the number of untreated older patients has decreased from 63% in 2005 to 45% in 2013, which may reflect the emergence of new and more tolerable therapies.
Given the different practice patterns and the lack of standard of care, we sought to better understand how older adults and oncologists (specifically community oncologists) make decisions about treatment. Our ultimate goal is to design a decision aid that facilitates discussion of treatment options, thereby reducing over- and under-treatment. In our abstract, we presented a framework illustrating the patient-, physician, disease/treatment-, and organizational factors that may affect clinical decisions in both older patients and oncologists. There were distinct factors that were considered by patients (e.g. quality of care and facility, trust in their oncologist/team) and by oncologists (e.g. local practice patterns, availability of transplant/clinical trials, their own clinical expertise and beliefs). Comorbidities, functional status, emotional health, and social support were important considerations but these were not routinely assessed in clinical practice. Therefore, we wanted to understand the barriers to performing fitness assessment in the community. The most common barriers cited by community oncologists were that 1) they do not think fitness assessment adds much to routine practice, 2) they have lack of time, resources, and expertise, 3) they have lack of awareness of the tools or the evidence that support its use, and 4) impairments are usually noted by other team members before they see the patients. Our findings could guide the development of interventions to increase the adoption of fitness assessments in community oncology practices.
Under-treatment of older adults also extends to allogeneic hematopoietic stem cell transplant (HSCT). We presented another abstract looking at the barriers to allogeneic HSCT in adults with hematologic malignancies systematically. Of the 23 studies included, only one had a subgroup analysis on older adults. We found that age was the most common barrier to allogeneic HCT. While allogeneic HCT may not be appropriate in old-old patients (>75 years), those who aged ≤75 years may derive benefits, as demonstrated in an abstract by Medeiros et al. using the SEER-Medicare database.
In summary, I am excited to be in the field of geriatric hematology and I am grateful to all my mentors (including Drs. Supriya Mohile, Heidi Klepin, Karen Mustian, and Wendy Stock), the entire geriatric oncology team at the University of Rochester Medical Center, and my geriatric oncology colleagues/friends. I also want to thank the ASH Clinical Research Training Institute through which I met many experts and friends in the field of Hematology.
Kah Poh (Melissa) Loh, MBBCh is a board-certified internist and hematologist. She is completing her Geriatrics Fellowship at the University of Rochester Medical Center and will begin her faculty appointment in July 2019 as a geriatric hematologist/oncologist at the James P. Wilmot Cancer Center. She can be reached at firstname.lastname@example.org