Page 139 - Haematologica May 2022

Prephase therapy in older patients with DLBCL
ADL and IADL, and social activity limitation. They were also significantly associated with increased TUG time, CARG chemotherapy toxicity risk, and baseline LDH level.
We next examined the impact of prephase treatment on GA measures and CK levels. As shown in Table 3, prephase therapy led to significant reduction in levels of IL-10 (q=0.033), IL-4 (q=0.04), IL-6 (q=0.01), and TNF-a (q=0.01). The magnitude of changes was most pro- nounced for TNF-a and IL-6 (Online Supplementary Figure S1). Prephase therapy did not lead to significant changes in GA measures within the 2-week period (Table 3),
although there was a trend of improvement in clinician rated KPS and CARG chemotherapy toxicity risk score prior to correction for multiple testing. Neither baseline or changes in GA measures or CK levels differed by early ver- sus later stage of disease (Online Supplementary Tables S3 and S4).
Association of geriatric assessment and cytokines with outcomes
Finally, we examined the association of both baseline and changes in GA measures and CK levels following prephase therapy with outcomes. As shown in Table 4, we did not find a significant association of any baseline or changes in GA measures with the development of TE, although there was a trend toward significance for base- line CARG risk score (P=0.040) and the absolute toxicity risk percentage (P=0.019) prior to correction for multiple testing. Similarly, there was no significant association between baseline or changes in cytokine levels with the development of TE, although there was a trend toward significance for baseline IL-10 (P=0.012) and IL-13 (P=0.006) prior to correction for multiple testing (Online Supplementary Table S5). Due to the small number of PFS/OS events (n=6), we did not assess the association of GA measures and CK levels with these outcomes.
Discussion
Improving outcomes for older, vulnerable patients with aggressive lymphoma has remained a challenge over the last few decades. In this study, we examined a novel ritux- imab/prednisone prephase therapy for older, vulnerable DLBCL patients prior to curative, anthracycline-based chemoimmunotherapy. This prephase therapy was feasi- ble with acceptable toxicity profiles. Most patients in this vulnerable cohort completed the planned 4-6 cycles of treatment, although dose reduction/delays were common. Although conclusions are limited by the pilot nature of the study with small sample size, the favorable 5-year survival of over 80% was comparable to selected historical
Table 1. Baseline characteristics.
Age, years, median (range) Female sex, n (%)
Stage, n (%)
I/II
III/IV
Cell of origin (n=31), Hans, n (%)
GCB
Non-GCB Histology, n (%)
De novo
Transformed follicular
Richter’s transformation Age-adjusted IPI, n (%)
Low/Int-1
Int-2/High
Induction regimen, n (%)
R-CHOP R-mini-CHOP R-EPOCH
No treatment
Comorbidity, n (%) Low
Intermediate
High
Clinician rated KPS, median (range)
Patient rated KPS, median (range)
ADL score, median (range)
IADL score, median (range)
Activity limitation score, median (range)
Number of falls last 6 months, median (range)
TUG in seconds, median (range)
Cognition score (BOMC), median (range)
Mini-nutritional assessment, median (range)
CARG score, median (range)
CARG % risk, median (range)
Total cohort (N=33)
75 (65-87) 20 (61)
13 (39) 20 (61)
18 (58) 13 (42)
29 (88) 3 (9) 1 (3)
14 (42) 19 (58)
29 (91) 1 (3) 2 (6) 1
10 (30) 17 (52)
6 (18) 80 (40-100) 80 (40-100) 65 (0-100) 14 (2-14) 50 (25-75) 0 (0-9) 11.31 (5-40) 2 (0-10) 23 (10.5-30) 10 (6-17) 54 (32-89)
Table 2. Toxicity events and high-grade toxicities. Category of events
Toxicity events (unplanned hospitalization, chemotherapy discontinuation, and/or dose reduction/delay)
Severe toxicity events
(unplanned hospitalization and/or chemotherapy discontinuation)
Early induction death (prior to cycle 3) Category of toxicities
Grade 3+ hematologic toxicities
Grade 4+ hematologic toxicities
Grade 3+ non-hematologic toxicities Grade 3+ non-hematologic toxicities plus Grade 4+ hematologic toxicities
Number of patients (%)
22 (67) 12 (36)
1 (3)
23 (70) 6 (18) 16 (48) 16 (48)
GCB: germinal center B-cell type; IPI: international prognostic index; R-CHOP: Rituximab, Cyclophosphamide, Doxorubicin hydrochloride, Vincristine sulfate, Prednisone; R-EPOCH: Rituximab, Etoposide phosphate, Prednisone, Vincristine sul- fate, Cyclophosphamide, Doxorubicin hydrochloride; KPS: Karnofsky performance scale; ADL: activities of daily living; IADL: instrumental activities of daily living; TUG: timed-get-up and go; BOMC: Blessed Orientation Memory Concentration; CARG: can- cer and aging research group.
Total numbers of grade 3+ non-hematologic toxicities: infection (10); cardiac (5); electrolyte/metabolic (3); gastrointestinal/nutrition (3); bleeding/thrombosis (2); infusion reaction (1); psychiatric (1).
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