Geriatric assessment for older adults receiving less-intensive therapy for acute myeloid leukemia: report of CALGB 361101

Ellen K Ritchie, Heidi D Klepin, Elizabeth Storrick, Brittny Major, Jennifer Le-Rademacher, Martha Wadleigh, Alison Walker, Richard A Larson, Gail J Roboz, Ellen K Ritchie, Heidi D Klepin, Elizabeth Storrick, Brittny Major, Jennifer Le-Rademacher, Martha Wadleigh, Alison Walker, Richard A Larson, Gail J Roboz

Abstract

Geriatric assessment (GA) predicts survival among older adults with acute myeloid leukemia (AML) treated intensively. We evaluated the predictive utility of GA among older adults treated with low-intensity therapy on a multisite trial. We conducted a companion study (CALGB 361101) to a randomized phase 2 trial (CALGB 11002) of adults ≥60 years and considered "unfit" for intensive therapy, testing the efficacy of adding bortezomib to decitabine therapy. On 361101, GA and quality of life (QOL) assessment was administered prior to treatment and every other subsequent cycle. Relationships between baseline GA and QOL measures with survival were evaluated using Kaplan-Meier estimation and Cox proportional hazards models. One-hundred sixty-five patients enrolled in CALGB 11002, and 96 (52%) of them also enrolled in 361101 (median age, 73.9 years). Among participants, 85.4% completed ≥1 baseline assessment. In multivariate analyses, greater comorbidity (hematopoietic cell transplantation-specific comorbidity index >3), worse cognition (Blessed Orientation-Memory-Concentration score >4), and lower European Organization for Research and Treatment of Cancer global QOL scores at baseline were significantly associated with shorter overall survival (P < .05 each) after adjustment for Karnofsky Performance Status, age, and treatment arm. Dependence in instrumental activities of daily living and cognitive impairment were associated with 6-month mortality (hazard ratio [HR], 3.5; confidence interval [CI], 1.2-10.4; and HR, 3.1; CI, 1.1-8.6, respectively). GA measures evaluating comorbidity, cognition, and self-reported function were associated with survival and represent candidate measures for screening older adults planned to receive lower-intensity AML therapies. This trial was registered at www.clinicaltrials.gov as #NCT01420926 (CALGB 11002).

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Diagram of enrollment and follow-up on A361101.
Figure 2.
Figure 2.
Kaplan-Meier curve of OS by cognitive test score.

References

    1. National Cancer Institute. Cancer stat facts: leukemia — acute myeloid leukemia (AML). . Accessed 15 October 2020.
    1. Sekeres MA, Guyatt G, Abel G, et al. . American Society of Hematology 2020 guidelines for treating newly diagnosed acute myeloid leukemia in older adults. Blood Adv. 2020;4(15):3528-3549.
    1. DiNardo CD, Pratz K, Pullarkat V, et al. . Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7-17.
    1. Ferrara F, Barosi G, Venditti A, et al. . Consensus-based definition of unfitness to intensive and non-intensive chemotherapy in acute myeloid leukemia: a project of SIE, SIES and GITMO group on a new tool for therapy decision making. Leukemia. 2013;27(5):997-999.
    1. Klepin H, Ritchie K, Sanford B, et al. . Feasibility of geriatric assessment for older adults with acute myeloid leukemia (AML) receiving intensive chemotherapy on a cooperative group trail: CALGB 361006 (Alliance). In: ASCO Annual Meeting; 2014; Chicago, IL.
    1. Klepin HD, Geiger AM, Tooze JA, et al. . Geriatric assessment predicts survival for older adults receiving induction chemotherapy for acute myelogenous leukemia. Blood. 2013;121(21):4287-4294.
    1. Hamaker ME, Prins MC, Stauder R. The relevance of a geriatric assessment for elderly patients with a haematological malignancy--a systematic review. Leuk Res. 2014;38(3):275-283.
    1. Mohile SG, Dale W, Somerfield MR, et al. . Practical assessment and management of vulnerabilities in older patients receiving chemotherapy: ASCO guideline for geriatric oncology. J Clin Oncol. 2018;36(22):2326-2347.
    1. Mohile SG, Epstein RM, Hurria A, et al. . Communication with older patients with cancer using geriatric assessment: a cluster-randomized clinical trial from the National Cancer Institute Community Oncology Research Program. JAMA Oncol. 2020;6(2):196-204.
    1. Scheepers ERM, Vondeling AM, Thielen N, van der Griend R, Stauder R, Hamaker ME. Geriatric assessment in older patients with a hematologic malignancy: a systematic review. Haematologica. 2020;105(6):1484-1493.
    1. Klepin HD, Geiger AM, Tooze JA, et al. . The feasibility of inpatient geriatric assessment for older adults receiving induction chemotherapy for acute myelogenous leukemia. J Am Geriatr Soc. 2011;59(10):1837-1846.
    1. Klepin HD, Ritchie E, Major-Elechi B, et al. . Geriatric assessment among older adults receiving intensive therapy for acute myeloid leukemia: report of CALGB 361006 (Alliance). J Geriatr Oncol. 2020;11(1):107-113.
    1. Klepin HD, Tooze JA, Pardee TS, et al. . Effect of intensive chemotherapy on physical, cognitive, and emotional health of older adults with acute myeloid leukemia. J Am Geriatr Soc. 2016;64(10):1988-1995.
    1. 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. 2013;98(2):208-216.
    1. Min GJ, Cho BS, Park S-S, et al. . Geriatric assessment predicts non-fatal toxicities and survival for intensively treated elderly acute myeloid leukemia: a prospective study. Blood. 2022;139(11):1646-1658.
    1. Grishina O, Schmoor C, Döhner K, et al. . DECIDER: prospective randomized multicenter phase II trial of low-dose decitabine (DAC) administered alone or in combination with the histone deacetylase inhibitor valproic acid (VPA) and all-trans retinoic acid (ATRA) in patients >60 years with acute myeloid leukemia who are ineligible for induction chemotherapy. BMC Cancer. 2015;15:430.
    1. Roboz GJ, Mandrekar SJ, Desai P, et al. . Randomized trial of 10 days of decitabine ± bortezomib in untreated older patients with AML: CALGB 11002 (Alliance). Blood Adv. 2018;2(24):3608-3617.
    1. Uy GL, Mandrekar SJ, Laumann K, et al. . A phase 2 study incorporating sorafenib into the chemotherapy for older adults with FLT3-mutated acute myeloid leukemia: CALGB 11001. Blood Adv. 2017;1(5):331-340.
    1. Hurria A, Cirrincione CT, Muss HB, et al. . Implementing a geriatric assessment in cooperative group clinical cancer trials: CALGB 360401. J Clin Oncol. 2011;29(10):1290-1296.
    1. Hurria A, Gupta S, Zauderer M, et al. . Developing a cancer-specific geriatric assessment: a feasibility study. Cancer. 2005;104(9):1998-2005.
    1. Sorror ML, Maris MB, Storb R, et al. . Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005;106(8):2912-2919.
    1. Veit CT, Ware JE Jr. The structure of psychological distress and well-being in general populations. J Consult Clin Psychol. 1983;51(5):730-742.
    1. Giles FJ, Borthakur G, Ravandi F, et al. . The haematopoietic cell transplantation comorbidity index score is predictive of early death and survival in patients over 60 years of age receiving induction therapy for acute myeloid leukaemia. Br J Haematol. 2007;136(4):624-627.
    1. Sorror ML, Giralt S, Sandmaier BM, et al. . Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences. Blood. 2007;110(13):4606-4613.
    1. Podsiadlo D, Richardson S. The timed “up & go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39(2): 142-148.
    1. Katzman R, Brown T, Fuld P, Peck A, Schechter R, Schimmel H. Validation of a short orientation-memory-concentration test of cognitive impairment. Am J Psychiatry. 1983;140(6):734-739.
    1. Aaronson NK, Ahmedzai S, Bergman B, et al. . The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365-376.
    1. Kornblith AB, Herndon JE II, Silverman LR, et al. . Impact of azacytidine on the quality of life of patients with myelodysplastic syndrome treated in a randomized phase III trial: a Cancer and Leukemia Group B study. J Clin Oncol. 2002;20(10):2441-2452.
    1. Therneau TM, Grambsch PM, eds. Modeling Survival Data: Extending the Cox Model. 1st ed. New York, NY: Springer-Verland New York; 2000. Statistics for Biology and Health.
    1. Etienne A, Esterni B, Charbonnier A, et al. . Comorbidity is an independent predictor of complete remission in elderly patients receiving induction chemotherapy for acute myeloid leukemia. Cancer. 2007;109(7):1376-1383.
    1. Sorror ML, Sandmaier BM, Storer BE, et al. . Comorbidity and disease status based risk stratification of outcomes among patients with acute myeloid leukemia or myelodysplasia receiving allogeneic hematopoietic cell transplantation. J Clin Oncol. 2007;25(27):4246-4254.
    1. Sorror ML, Storer BE, Fathi AT, et al. . Development and validation of a novel acute myeloid leukemia-composite model to estimate risks of mortality. JAMA Oncol. 2017;3(12):1675-1682.
    1. Hshieh TT, Jung WF, Grande LJ, et al. . Prevalence of cognitive impairment and association with survival among older patients with hematologic cancers. JAMA Oncol. 2018;4(5):686-693.
    1. Olin RL, Fretham C, Pasquini MC, et al. . Geriatric assessment in older alloHCT recipients: association of functional and cognitive impairment with outcomes. Blood Adv. 2020;4(12):2810-2820.
    1. Jayani RV, Magnuson AM, Sun CL, et al. . Comprehensive geriatric assessment predicts azacitidine treatment duration and survival in older patients with myelodysplastic syndromes. J Geriatr Oncol. 2020;11(1):114-120.
    1. Molga A, Wall M, Chhetri R, et al. . Comprehensive geriatric assessment predicts azacitidine treatment duration and survival in older patients with myelodysplastic syndromes. J Geriatr Oncol. 2019.
    1. Sherman AE, Motyckova G, Fega KR, et al. . Geriatric assessment in older patients with acute myeloid leukemia: a retrospective study of associated treatment and outcomes. Leuk Res. 2013;37(9):998-1003.
    1. DuMontier C, Loh KP, Soto-Perez-de-Celis E, Dale W. Decision making in older adults with cancer. J Clin Oncol. 2021;39(19):2164-2174.

Source: PubMed

3
구독하다