The Addition of CT Scans to NCI-96 Chronic Lymphocytic Leukemia (CLL) Response Criteria Fails To Improve the Predictive Power of Complete Response (CR) and Partial Response (PR) as Assessed by Improvement in Progression-Free (PFS) and Overall Survival (OS) .
Authors: Blum Kristie A. , Young Donn , Broering Sarah , Lucas Margaret S. , Lin Thomas S. , Grever Michael R. , Byrd John C. 
Published: October 2019

Abstract
Background: NCI-sponsored working group (NCI-WG) criteria for response assessment in CLL (Blood1996:87; 4990–4997) rely on physical examination, blood, and bone marrow evaluations, with no requirement for CT scan measurements. Recent improvements in CLL therapy provide justification for re-evaluation of these response criteria.
Methods: In a retrospective review of 3 ongoing trials at The Ohio State University in patients (pts) with symptomatic untreated (8) and previously treated (74) CLL, we assessed response in pre- and post-treatment CT scans using international non-Hodgkin’s lymphoma (NHL) CT response criteria (JCO1999:17;1244–1253). These results were compared to response determined by conventional NCI-WG criteria.
Results: In 82 pts, the median age was 60 (range, 38–84), with 60 males. The majority of pts had Rai stage IV disease (39), with a median of 4 prior therapies (range 0–14). Response according to NCI-WG criteria were as follows: CR 5 (6.1%), PR 32 (39%), SD 21 (25.6%), PD 17 (20.7%), and not evaluable (NE) 7 (8.5%). Response by NHL CT criteria were as follows: CR 3 (3.7%), CRu 12 (14.6%), PR 16 (19.5%), SD 26 (31.7%), PD 4 (4.9%), and NE 21 (25.6%). 23 pts were NE by either NCI-WG or NHL CT criteria due to lack of a post-treatment CT or early treatment-related toxicity. The table below provides the discrepancies in response assessment between NCI-WG and NHL CT criteria in the 59 evaluable pts. In all 82 pts, the median OS and PFS were 25.2 mos and 9.0 mos, respectively. In the 75 pts evaluable by NCI-WG criteria, CR, PR, SD, and PD response designations correlated with PFS (p=0.001) by log-rank test, with a median PFS of 27.3 mos for CR, 11.4 mos for PR, 5.6 mos for SD, and 2.5 mos for PD. Response by NCI-WG criteria also correlated with OS (p=0.012), with 12 deaths reported. For the 61 pts evaluable by NHL CT criteria, log-rank test demonstrated a significant correlation with CR, PR, SD, and PD designations and PFS (p=0.001); however, there was no difference between CRu and PR. For pts achieving a CRu, PFS was 11.7 mos; compared to 14.7 mos for a PR, and 18.4 mos for a CR. NHL CT criteria also correlated with OS (p=0.001), with 6 deaths reported. In multi-variate cox regression analysis, NCI-WG CLL response, NHL CT response, age, Rai stage, and number of prior therapies failed to correlate with OS (p-values=0.382–0.999). However, with the same variables, NCI-WG CLL response was the only significant predictor of PFS (p=0.005), with no significant association between NHL CT response and PFS (p=0.061).
Conclusions: These results support current NCI-WG CLL criteria as a significant predictor of response and ultimately PFS in pts with previously treated CLL, with no additional benefit from the inclusion of CT scans. In addition, the CRu response definition has limited prognostic value in CLL, as PFS in this group is similar to those pts achieving PR. Limitations of this study include retrospective design, low CR rate, and a high proportion of previously treated pts. These results nonetheless highlight the importance of prospective validation of CT scans before routine inclusion in response criteria for CLL.
Response by NHL CT criteria CR CRu PR SD PD Totals Response by NCI-WG criteria CR 3 2 0 0 0 5 PR 0 8 14 8 0 30 SD 0 2 1 9 1 13 PD 0 0 0 8 3 11 Totals 3 12 15 25 4 59