Stuart M. Lichtman, MD
Geriatrics for the Oncologist is guest edited by Stuart M. Lichtman, MD, and developed in collaboration with the International Society of Geriatric Oncology (SIOG). Dr. Lichtman is an Attending Physician at Memorial Sloan Kettering Cancer Center, Commack, New York, and Professor of Medicine at Weill Cornell Medical College, New York. He is also President of SIOG. For more information about geriatric oncology, visit www.siog.org and the ASCO Geriatric Oncology website (www.asco.org/practice-guidelines/cancer-care-initiatives/geriatric-oncology/geriatric-oncology-resources).
Many exciting studies were presented at the 2018 American Society of Hematology (ASH) Annual Meeting & Exposition and were covered in previous issues of The ASCO Post. In addition to a scientific workshop dedicated to hematology and aging, many abstracts focused specifically on older adults, and a few of these studies are featured here.
Chronic Lymphocytic Leukemia
In the Plenary Session, Woyach et al presented the results of a randomized phase III trial that evaluated bendamustine/rituximab, ibrutinib alone, and ibrutinib/rituximab in patients 65 years of age or older with untreated chronic lymphocytic leukemia (CLL).1 (These findings were published simultaneously in TheNew England Journal of Medicine.2) The 2-year progression-free survival was 74%, 87%, and 88%, respectively. Compared with bendamustine/rituximab, the hazard ratio for disease progression or death was lower with ibrutinib alone (0.39, 95% confidence interval [CI] = 0.26–0.59) or ibrutinib/rituximab (0.38, 95% CI = 0.25–0.59). There was no progression-free survival difference between patients
Kah Poh (Melissa) Loh, MBBCh, BAO
treated with ibrutinib alone or ibrutinib/rituximab. There was no overall survival difference after a median follow-up of 38 months among the three arms. Grade 3 or 4 hematologic adverse events were more common with bendamustine/rituximab (61% vs 39%–41% with ibrutinib), whereas grade 3 to 5 nonhematologic adverse events were more common in the ibrutinib arms (74% vs 63% in the bendamustine/rituximab arm).
This trial suggests that ibrutinib alone should be used as an upfront treatment for older patients with CLL, but the exact duration needs to be further investigated, and consideration should be given to the financial cost associated with indefinite therapy. Of note, patients underwent a geriatric assessment in this study; although the association between variables from this assessment and outcomes was not presented, these data would be valuable.
Acute Myeloid Leukemia
Prior research suggests that less than 40% of older patients with acute myeloid leukemia (AML) receive disease-directed therapy in the United States. Fortunately, Medeiros et al showed that the percentage of untreated patients has significantly decreased from 63% in 2005 to 45% in 2013.3 Not surprisingly, receipt of therapy is associated with improved survival. This trend is encouraging and is likely due in part to the increasing availability of novel therapeutic agents that are more efficacious and tolerable.
Not only should the treatments of tomorrow be selected on the basis of disease and tumor molecular profiling, but also on the underlying health and physiologic age of the patient.— Kah Poh (Melissa) Loh, MBBCh, BAO
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The combination of venetoclax with low-dose cytarabine or a hypomethylating agent was recently approved for the treatment of AML in the front-line setting for patients 75 years of age or older or for those who are not candidates for induction treatment. Maiti et al evaluated venetoclax and 10-day decitabine in 48 patients with AML; half were 60 years of age or older and untreated.4 In this older subgroup, the overall complete response/complete response with incomplete count recovery rate was 92%, and there were no early deaths. In the entire cohort, 31 patients experienced a total of 59 treatment-emergent adverse events; 48 of them were grade 3 or 4.
The trial is currently ongoing, but the early results are promising. Given that hematopoietic stem cell transplant (HSCT) is generally the only curative option for patients with AML, this combination may serve as a bridge to HSCT.
Geriatric Assessment in AML Clinical Trials
In other interesting research, Sorror et al conducted a prospective multicenter longitudinal study in 696 patients and compared the survival of those who did and did not receive HSCT.5 In addition to disease-associated variables, geriatric assessment variables such as cognition, quality of life, social support, and depression were also collected. In unadjusted analyses, HSCT was shown to be associated with improved survival, but this association was lost after the investigators adjusted for disease-specific and geriatric assessment variables. This adds to the uncertainty over whether HSCT is beneficial for older adults and suggests the need to include vulnerable patients when designing clinical trials.
For more information on improving communication with older patients with cancer using geriatric assessment, see an interview with Supriya G. Mohile, MD, on The ASCO Post Newsreels at ascopost.com/videos.
Geriatric assessment has been shown to predict toxicity and outcomes, although it is not widely used in treating patients with cancer and even less so for those with hematologic malignancies. In the DECIDER trial, Hupfer et al derived a frailty score based on the Eastern Cooperative Oncology Group performance status, activities of daily living (the Barthel index), and fatigue (European Organisation for Research and Treatment Quality-of-Life questionnaire) and then tested it in “nonfit” patients older than age 60 with AML who received decitabine-based therapy.6 Patients were grouped into three risk categories based on the frailty score (0 vs 1 vs 2–3). The corresponding median overall survival was approximately 12 months, 6 months, and 3 months, respectively.
This work is an extension of a previously published study, which demonstrated the predictive value of functional status and fatigue.7 Nonetheless, there are many reported barriers to the use of geriatric assessment in routine clinical practice, including perceived lack of utility; lack of time, resources, and expertise; and lack of awareness of the tools or evidence to support its use.8 Therefore, there is a need to improve education about and availability of geriatric assessment.
With novel therapeutic options emerging at an unprecedented pace for older patients with hematologic malignancies, we need to be able to take a more individualized approach for older adults. Not only should the treatments of tomorrow be selected on the basis of disease and tumor molecular profiling, but also on the underlying health and physiologic age of the patient. ■
Dr. Loh is a geriatric hematologist/oncologist at the University of Rochester Medical Center, Rochester, New York.
DISCLOSURE: Dr. Loh reported no conflicts of interest.
1. Woyach JA, Ruppert AS, Heerema NA, et al: Ibrutinib alone or in combination with rituximab produces superior progression free survival compared with bendamustine plus rituximab in untreated older patients with chronic lymphocytic leukemia: Results of Alliance North American Intergroup Study A041202. 2018 ASH Annual Meeting & Exposition. Abstract 6.
2. Woyach JA, Ruppert AS, Heerema NA, et al: Ibrutinib regimens versus chemoimmunotherapy in older patients with untreated CLL. N Engl J Med 379:2517-2528, 2018.
3. Medeiros BC, Satram-Hoang S, Momin F, et al: Real-world treatment patterns and comparative effectiveness among a population of elderly patients with acute myeloid leukemia. 2018 ASH Annual Meeting & Exposition. Abstract 835.
4. Maiti A, DiNardo CD, Cortes JE, et al: Interim analysis of phase II study of venetoclax with 10-day decitabine in acute myeloid leukemia and myelodysplastic syndrome. 2018 ASH Annual Meeting & Exposition. Abstract 286.
5. Sorror ML, Storer BE, Gerds AT, et al: Survival differences among patients with acute myeloid leukemia treated with allogeneic hematopoietic cell transplantation (HCT) versus non-HCT therapies: A large real-time multi-center prospective longitudinal observational study. 2018 ASH Annual Meeting & Exposition. Abstract 207.
6. Hupfer V, Grishina O, Schmoor C, et al: Validation of a frailty score predicting survival of elderly, non-fit AML patients receiving hypomethylating therapy: Results of the DECIDER trial. 2018 ASH Annual Meeting & Exposition. Abstract 720.
7. Deschler B, Ihorst G, Platzbecker U, et al: Parameters detected by geriatric and quality of life assessment in 195 older patients with myelodysplastic syndromes and acute myeloid leukemia are highly predictive for outcome. Haematologica 98:208-216, 2013.
8. Loh KP, Kadambi S, Mohile SG, et al: Qualitative study of factors that influence treatment decision-making among community oncologists and older patients with acute myeloid leukemia. 2018 ASH Annual Meeting & Exposition. Abstract 2246.