Page 142 - Haematologica May 2022

R.J. Lin et al.
Figure 3. Heatmap of significant correlations of baseline geriatric assessment measures with baseline proinflammatory cytokine levels (q<0.05) with blue color demonstrating significant positive association and red color demonstrating significant negative association. LDH: lactate dehydrogenase; KPS: Karnofsky perform- ance scale; ADL: activities of daily living; IADL: instrumental activities of daily living; TUG: timed-get-up and go; CARG: cancer and aging group; IFN: interferon; IL: inter- leukin; TNF: tumor necrosis factor.
underlying mechanism has never been examined and vin- cristine has significant neurotoxicity especially for older adult thus making it a poor partner of prednisone.10 Rituximab is likely more effective as a cytoreductive and debulking agent than vincristine at a dose of 1 mg; concur- rently, however, we acknowledge concern for rituximab toxicities which include infusion related reactions that at times can be severe. We showed that this regimen led to an acceptable rate of 48% grade 3+ non-hematologic plus grade 4+ hematologic toxicities in this vulnerable cohort of older patients who were at high risk for chemotherapy- related toxicities. Importantly, most patients in our cohort were able to complete planned cycles of curative, anthra- cycline-based chemoimmunotherapy and there was one early cycle death. Therefore, it is not surprising that our cohort of patients had outstanding PFS and OS. However, while we had hoped to see a decrease in mortality/toxici- ty from the prephase treatment, we could not directly compare survival and toxicity results from this pilot study with small sample size to previous large trials and registry studies.7-9,22,23 In addition, with this design we cannot ascertain if rituximab’s addition to prednisone added ben- efit, although the additional dose of rituximab did not appear to add toxicity.
Among hematologic malignancies including lymphoma, GA domains including function, mobility, cognition, and comorbidity have been consistently shown to be associat- ed with survival and/or treatment-related toxicities.24-27 Our study is the first to examine specifically the CARG chemotherapy risk score in lymphoma patients and its
longitudinal changes. The CARG score is easy to derive and well validated in solid tumors, however, its dynamic changes in response to therapy is unknown.13,14 In our study, we were unable to demonstrate a significant change in GA measures pre- and post-prephase therapy. It is pos- sible that the short time interval, less than 2 weeks on average, is not adequate to detect a significant change in GA domains such as functional status. Indeed, a recent study in acute myeloid leukemia patients measured GA changes 8-12 weeks following the initial assessment.28 Alternatively, our sample size may be too small or that prephase treatment alone is inadequate to impact GA changes. Interestingly, there was a suggestion of an asso- ciation between the baseline CARG risk score and the absolute chemotherapy toxicity risk with TE, which will be explored further. Nevertheless, given accumulating evi- dence of how geriatric frailty affects older lymphoma patients,29,30 our longitudinal GA data may allow in-depth examination of the prognostic impact of both baseline and changes in individual geriatric deficits, and may also be used prospectively to guide treatment-decision making in older, vulnerable lymphoma patients as shown in previous studies.31-34
Perhaps the most interesting aspect of our findings is the SASP-associated, proinflammatory cytokine milieu and its relationship to GA and prephase therapy. A few key cytokines in this age-related SASP such as IL-6, TNF- a, IL-10, and IL-2 were strongly associated with geriatric impairments including functional limitations in
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