Multicenter analysis of geriatric fitness and real-world outcomes in older patients with classical Hodgkin lymphoma

Abstract

We performed a multicenter retrospective analysis across 10 US academic medical centers (2010 - 2018) to evaluate current treatment patterns and outcomes in patients age ≥60 with classical Hodgkin lymphoma (cHL). Among 244 eligible patients, median age was 68, 63% had advanced stage (III/IV), 14% had ECOG performance status (PS) 2-4, and 12% had documented loss of ≥1 activity of daily living (ADLs). Medical comorbidities were assessed by the Cumulative Illness Rating Scale - Geriatric (CIRS-G), where n=44 (18%) had total scores ≥10. Using multivariable Cox models, only ADL loss predicted shorter progression-free (PFS; HR 2.13, p=0.007) and overall survival (OS; HR=2.52, P=0.02). Most patients (n=203, 83%) received conventional chemotherapy regimens, including ABVD (56%), AVD (14%), and AVD with brentuximab vedotin (BV; 9%). Compared to alternative therapies, conventional regimens significantly improved PFS (HR 0.46, P=0.0007) and OS (HR 0.31, p=0.0003). Survival was similar following conventional chemotherapy in those ages 60-69 vs ≥70: PFS HR 0.88, p=0.63; OS HR 0.73, p=0.55. Early treatment discontinuation due to toxicity was more common with CIRS-G ≥10 (28 vs 12%, p=0.016) or documented geriatric syndrome (28 vs 13%, p=0.02). A competing risk analysis demonstrated improved disease-related survival with conventional therapy (HR 0.29, p=0.02) and higher mortality from causes other than disease or treatment in those with high CIRS-G or geriatric syndromes. These data suggest conventional chemotherapy regimens be considered standard of care in fit older patients with cHL, and highlights the importance of geriatric assessments in defining fitness for cHL therapy going forward.

The outcome of older adults with classic Hodgkin lymphoma in British Columbia

“… 13 , 21 The importance of comorbidity measures was highlighted in a recent multicenter analysis, which reported higher rates of toxicity-related early treatment discontinuation in older adults with a Cumulative Illness Rating Scale-Geriatric score ≥10 (28% vs 12%, P = .016) or with documented geriatric syndrome (28% vs 13%, P = .02) treated with conventional therapy, as well as higher mortality from causes other than disease or treatment. 22 …”

Novel Agents For Relapsed and Refractory Classical Hodgkin Lymphoma: A Review

“…cHL in patients over 60 years of age is highly linked to poorer prognosis since these patients generally suffer from inferior efficacy but great toxicity, owing to comorbidity and geriatric fitness ( 12 ). The management of older patients should be individualized and usually requires clinical judgment.…”

Clinical Dilemmas in the Treatment of Elderly Patients Suffering from Hodgkin Lymphoma: A Review

“…Interestingly, disability status was not found to be a significant predictor, possibly due to patient selection bias (i.e., only fit patients offered ABVD regimen). Orellana-Noia et al carried out research across 10 medical centers in the US ( n = 244) and showed that superior outcomes were obtained after treatment with the conventional regimens compared to alternative therapies [ 11 ]. In a multivariate analysis, only loss of ADL was found to be predictive of poorer OS (HR = 2.13).…”

“…The actual incidence of BILI in elderly patients with HL is not known, with variable rates reported due to the use of retrospective study designs and reporting biases [ 11 , 30 , 43 , 51 , 52 ]. Concerning prospective trials, only Evens et al used exact methods for testing pulmonary lung function [ 43 ].…”

“… Abbreviations: ASCO—American Society for Clinical Oncology; CIRS-G—Cumulative Illness Rating Scale-Geriatric; HCT-CI—Hematopoietic Cell Transplantation-Specific Comorbidity Index; GA—geriatric assessment; G8: the G8 (Geriatric 8) Health Status Screening Tool; ADL—activities of daily Life; IADL— instrumental activities of daily life; GDS— Geriatric Depression Scale; SMM—Skeletal Muscle Mass; CT—Computed Tomography; PET-CT—Positron Emission Tomography-Computed Tomography; GRI—Global Risk Indicator; CARG: Cancer and Aging Research Group. Footnotes: * value of CIRS-G score as a prognostic factor in multivariate analyses varies; ** not predictive in first-line treatment of HL; see text for explanation and Orellana-Noia [ 11 ]; *** simplified tool used to assess GS; **** index for IADL proposed by the ASCO guidelines that has not been studied in aggressive lymphomas; ***** only two indexes have been validated in a population with cancer; ****** based on reviewed research, where depression was studied in various aggressive lymphomas, but there is no study focusing on elderly patients; ******* mixed results found regarding its prognostic value due to the modality used—in DLBCL studies conducted in patients receiving the CHOP-R regimen, it had a clear value for use in prognosis (study type: meta-analysis). …”