Page 138 - Haematologica May 2022

R.J. Lin et al.
GA measures and CK levels were assessed with the Spearman’s rank correlation coefficient. Progression-free survival (PFS) was calculated from treatment initiation to disease progression or death. Overall survival (OS) was calculated from diagnosis to death. All tests were corrected for multiple testing with the false discovery rate (q-value) at a significance level of 0.05. Statistical analyses were conducted in R Version 4.0.0.
Results
Patient characteristics
Baseline characteristics are summarized in Table 1. The cohort consisted of 33 patients with a median age of 75 years (range, 65–87) and ten patients (30%) were 80 years old or older. Nearly two thirds of patients were stage III and IV at diagnosis and more than half had intermediate- 2/high risk-disease based on age-adjusted International Prognostic Index (AA-IPI). All patients completed prephase treatment with rituximab and prednisone, with 26 patients full 100 mg dose and 7 patients 50 mg doses. One patient did not receive chemoimmunotherapy fol- lowing prephase treatment due to rapid disease progres- sion. For the 32 patients who initiated chemoim- munotherapy, 23 of 25 patients (92%) completed all six planned cycles; six of six completed all four planned cycles; and there was one early death due to rapid disease progression.
Baseline GA revealed that 23 patients (70%) had inter- mediate to high comorbidity burden. There were signifi- cant functional limitations in ADL (median 65; range, 0– 100), IADL (median 14, range, 0–14), and social activities (median 50; range 25–75). The median TUG time was 11.31 seconds (range, 5–40), with <10 seconds denoting no mobility limitation. The median MNA score was 23 (range, 10.5–30), with 15 patients (45%) considered at risk for malnutrition or malnourished (score >24). The median CARG chemotherapy toxicity risk score was 10 (range, 6– 17), corresponding to an absolute, grade 3+ chemothera- py-related toxicity risk of 54% (range, 32–89), both in the high-risk category.
Outcomes and toxicities
As shown in Figure 2, with a median follow-up of 4.4 (range, 0.4–5.7) years, both 5-year PFS and OS for the cohort were 81% (95% confidence interval [CI]: 69–96). PFS and OS according to AA-IPI is also shown in Figure 2. Among stage III/IV patients (n=20), the 5-year PFS and OS were both 74% (95% CI: 57–97, data not shown). Six patients died, including four from relapse/progression of disease and two while in remission. We summarized toxic events and high-grade CTATE toxicities through all treatment cycles in Table 2. TE and STE occurred in 22 patients (67%) and 12 patients (36%), respectively. The majority of TE was dose reduction/delay, occurring in 19 patients (58%). There were seven hospitalizations follow- ing cycle 1. Grade 3+ non-hematologic toxicities occurred in 16 patients (48%). The total number of grade 3+ non- hematologic toxicity was 26, including ten infections (3 following cycle 1), five cardiac toxicities, three elec- trolyte/metabolic toxicities, three gastrointestinal/nutri- tional toxicities, two hemorrhage/thrombosis, one infu- sion reaction, and one psychiatric illness. Grades 3+ and 4+ hematologic toxicities occurred in 23 patients (70%) and six patients (18%), respectively. Most toxicities, 17 (65%), was in cycle 1-3. In total, 16 patients (48%) had at least one grade 3+ non-hematological toxicity or grade 4+ hematologic toxicity. Toxicity events did not differ signif- icantly by stage of disease at diagnosis (Online Supplementary Table S1).
Geriatric assessment and senescence-associated secretory phenotype-associated proinflammatory cytokines
We examined the senescence-associated, proinflamma- tory cytokine milieu in our cohort of older patients and its relationship to clinical geriatric impairments. As shown in Figure 3 and the Online Supplementary Table S2, we found that levels of several proinflammatory cytokines were associated with individual geriatric impairment in older lymphoma patients. Specifically, elevated interleukin (IL)- 2, IL-6, IL-10, and TNF-a levels were significantly associ- ated with reduced KPS, functional limitation measured by
Figure 1. Study design. Prephase pilot embedded within a prospective, large cohort study of geriatric assessment in older patients with newly diagnosed non-Hodgkin lymphoma. DLBCL: diffuse large B-cell lymphoma; GA: geriatric assessment; NHL: non-Hodgkin lymphoma; KPS: Karnofsky performance scale; R-CHOP: rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone.
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