'Complete' Remission Strongly Affected by Use of CT Scanning

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[2834] Complete Remission in Chronic Lymphocytic Leukemia (CLL) Is

Strongly Affected by the Use of CT Scanning: Results from a

Prospective Randomized Trial of Fludarabine Plus Cyclophosphamide

(Flu/Cy) with or without Genasense (Oblimersen) in Patients with

Relapsed or Refractory Disease. Session Type: Poster Session, Board

#63-III

Maslak, Caravelli, Asher Alban Chanan-Khan Clinical

Laboratories, Memorial Sloan-Ketterting Cancer Center, New York, NY,

USA; Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY,

USA; Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

Literature in CLL has emphasized the importance of patient evaluation

with measures of minimal residual disease (MRD) by flow cytometry,

FISH, or RT-PCR after complete remission (CR). However, the widely

used National Cancer Institute-Working Group (NCI-WG) criteria for

response in CLL do not mandate the use of CT scanning or ultrasound

(US) for the evaluation of patients with abdominal lymphadenopathy.

Recently, the German CLL Study Group reported that the CR rate in

chemonave patients treated with fludarabine (Flu) alone or in

combination with cyclophosphamide (Flu/Cy) was reduced by almost one-

third when patients were routinely scanned using CT/US (Eichhorst et

al, Blood 2006).

We recently completed a randomized trial in patients with

relapsed/refractory CLL, which afforded an opportunity to examine the

impact of CT/US on residual disease in this setting.

Methods: Patients were randomized to treatment with Flu/Cy with or

without oblimersen. The primary objective was to determine the

proportion of patients who achieved CR or nodular partial response

(nPR) using NCI-WG criteria. Response and progression were

independently assessed by blinded expert review of clinical data,

radiology, and bone marrow histopathology. The protocol required that

patients with abnormalities on CT/US at study entry must have a

repeat CT/US in order to document CR/nPR. CT/US followup was not

required in pts who did not respond by other clinical criteria.

Results: At entry, 92 of 120 pts (77%) on the oblimersen arm and 97

of 121 pts (80%) on the Flu/Cy arm had baseline CT/US. These baseline

scans were abnormal in 88 (73%) and 90 (74%) of pts in each group,

respectively. Followup of patients with an initially abnormal scan

showed that repeat assessments (i.e., one or more followup CT/US)

were similar in each group: 71 pts (59%) in the oblimersen group and

66 (55%) of pts in the Flu/Cy group. The number of followup CT/US

(mean = 3; range = 1-14 for both groups), as well as the time between

followup scans was also balanced in pts receiving oblimersen (mean =

113 days; median = 97, range = 9-324) or Flu/Cy (mean = 125 days;

median = 121, range 5-327). The addition of oblimersen to Flu/Cy

significantly increased the proportion of pts who achieved a

confirmed CR/nPR (17% vs. 7%) when CT/US was required. To estimate

the incidence of CR/nPR when CT was omitted, we assumed that marrow

biopsy of pts with a histologically unconfirmed CR/nPR would have

shown CR/nPR. With that assumption, the estimated incidence of CR/nPR

(ie, absent the requirement for CT/US) increased to 25% and 14% for

pts treated with oblimersen and Flu/Cy, respectively.

Conclusion: CT or US appear to be widely used by clinicians who treat

CLL. Our results confirm and extend prior data that suggest the

routine use of CT or US reduces the CR or CR/nPR rates by

approximately 30% in both treatment-nave and previously treated pts

with CLL. These data argue that lack of mandatory abdominal CT/US

routinely results in an overestimation of CR/nPR incidence, and that

evaluation of MRD is potentially meaningful only in the context of

confirmed elimination of gross residual disease.