12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
with IT and patients without IT (RAI stage 0-2 in 91% vs 84% respectively,
p=0.16). First line treatment for CLL was similar in the two groups
consisting of Chlorambucil alone in 70% of patients. Five- and 10-year
overall survival (OS) for all patients was 73% and 50%. Patients with
CLL and IT experienced a significantly worst OS than other patients
with CLL (p=0.0006), as shown in the Figure 1. Refractoriness to treatment
for IT had an additional negative impact on survival. Conclusions.
Our study, for the first time, demonstrates that occurrence of IT in CLL
has a significant negative impact on survival, at variance with common
belief.
0122
CT SCAN GIVES ADDITIONAL INFORMATION OF CLINICAL VALUE IN PATIENTS WITH
CHRONIC LYMPHOCYTIC LEUKEMIA
N.E. Norin, 1 E. Kimby, 1 J. Lundin2 1 Karolinska University Hospital Huddinge, STOCKHOLM; 2 Karolinska
University Hospital Solna, STOCKHOLM, Sweden
Background. CLL is the most common chronic leukemia in adults and
shows an extremely variable prognosis. Traditional staging systems (Rai
and Binet) are based on clinical examination and presence of anemia
and/or thrombocytopenia. However, lymph node stations that are not
readily available for clinical examination such as abdominal and thoracic
lymph nodes are not incorporated in these staging systems, nor is spleen
enlargement not noted by palpation. These systems were developed
before CT scan became a routine method for obtaining information
about lymph node status in hematologic malignancies. We therefore
decided to analyse if CT scan would provide additional prognostic information
in CLL patients. Aims. To find out whether CT scan of thorax and
abdomen could provide additional prognostic information in patients
with CLL requiring first-line therapy. Methods. We identified 77 patients
who had been included in four phase II studies at Karolinska University
Hospital between 1990 and 2000. In these studies a CT scan was
mandatory before start of therapy and also for assessment of response
at the end of therapy. Data was retrospectively collected and analysed.
Assessment of response was based on information from the charts of the
patients using the NCI criteria. To obtain more detailed information of
lymph node status we also used the GELF criteria originally developed
for follicular lymphoma. Results. Time from CLL diagnosis to institution
of first-line therapy was 12 (0-269) months. The median age at this time
point was 66 (40-85) years and Rai stage was I (n=24), II (n=6), III (n=33)
or IV (n=14). With the addition of a CT scan lymphadenopathy and/or
splenomegaly was detected in totally 74 patients, leading to a modified
Rai stage in 9 patients, in all cases from I to II. CT scan also revealed
bulky (>7cm) abdominal lymphadenopathy in 11 patients. In total 54
patients had CT verified splenomegaly, in 22 cases this was not detected
during clinical examination. The time from first-line treatment to
start of next therapy was 29 months (1-156). Patients with a high lymphadenopathy
tumor burden according to the GELF criteria had a significantly
shorter time to therapy requirement than those with less
advanced lymphadenopathy (p=0.038). Summary and conclusions. Clinical
examination alone is not sufficient to rule out splenic enlargement
and abdominal lymphadenopathy in CLL. The degree of lymphadenopathy
appears to be of importance to predict duration of response to therapy.
CT might also be of value for evaluation of progression and the need
of further therapy. A larger study, preferably made at the time of CLL
diagnosis is warranted.
0123
THE COMBINATION OF LUMILIXIMAB AND FCR (FCRL) PRODUCES HIGH RATES OF
COMPLETE RESPONSE AND HAS COMPARABLE TOLERABILITY TO FCR IN PATIENTS WITH
RELAPSED CLL: RESULTS OF A PHASE I/II STUDY
J.C. Byrd, 1 J. Castro, 2 S. O'Brien, 3 I.W. Flinn, 4 A. Forero-Torres, 5
T.J. Kipps, 2 N.A. Heerema, 1 T. Lin, 1 K. Velastegui, 6 T. Kheoh, 6
A. Molina6 1 Ohio State University, COLUMBUS; 2 University of California, San Diego,
SAN DIEGO; 3 M.D. Anderson Cancer Center, HOUSTON; 4 Sarah Cannon
Research Institute, NASHVILLE; 5 University of Alabama Birmingham, BIRM-
INGHAM; 6 Biogen Idec, SAN DIEGO, USA
Background. Lumiliximab, an IgG1 chimeric monoclonal antibody targeting
CD23, has been shown to enhance fludarabine- and rituximabmediated
apoptosis in chronic lymphocytic leukemia (CLL) cells in a
caspase-dependent manner. Aims. A phase I/II open-label dose-escalation
multicenter study was initiated to evaluate the safety and efficacy of
44 | haematologica/the hematology journal | 2007; 92(s1)
lumiliximab in combination with fludarabine, cyclophosphamide, and
rituximab (FCR) in the treatment of relapsed CD23 + B-cell CLL. Methods.
Thirty-one patients with relapsed CD23 + B-cell CLL whose disease
was not refractory to FCR were enrolled after informed consent was
obtained. They were treated with 375 mg/m 2 (n=3) or 500 mg/m 2 (n=
28) of lumiliximab in combination with FCR for a maximum of 6 cycles.
Response was assessed using National Cancer Institute Working Group
criteria at weeks 13 and 25, and patients were to be followed for 48
months. Results. The median age of patients was 58 years. The median
absolute lymphocyte count was 41×10 3 /∝L and the median number of
previous regimens was 2 (range 1-9). Twenty-two patients (71%)
responded to treatment with FCR plus lumiliximab (FCRL); the complete
response rate was 52%. There were responses in 6 of 8 patients with
del(11q22.3), 5 of whom achieved a complete response. One of 4
patients with del(17p13.1) had a partial response to treatment. Grade 3
or 4 adverse events were reported in 65% of patients, but these events
were manageable and were expected with FCR therapy. The most common
adverse events (all grades) were nausea (77%), pyrexia (61%), neutropenia
(58%), chills (55%), and fatigue (48%). Data from the phase I/II
trial were compared with published data from a study in 177 patients
with relapsed or refractory CLL who were treated with FCR alone (Wierda
W, et al. J Clin Oncol. 2005;23:4070-4078). The characteristics of
patients treated with FCRL or FCR alone were comparable, with the
exception of Rai stage I/II disease (74% vs 47%) and previous exposure
to rituximab (60% vs 12%). The overall response rates were similar
with the 2 regimens (71% vs 73%), but FCRL produced a complete
response rate that was double the rate observed with FCR alone (52%
vs 25%). The regimens had similar incidence rates and levels of severity
of myelosuppression and other toxicities; approximately 45% of
patients in both studies completed 6 cycles of treatment. Conclusions.
These data suggest that lumiliximab administered in combination with
FCR has a high level of activity in the treatment of relapsed CLL. The
FCRL regimen has an acceptable safety profile and does not appear to
add to the toxicity of FCR. The complete response rate achieved with
FCRL appears encouraging, even in patients with del(11q22.3). A randomized
trial comparing FCRL with FCR alone has been initiated and
is currently enrolling patients.
0124
POST-REMISSIONAL RITUXIMAB ADMINISTRATION FOR THE TREATMENT OF OLDER
CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) PATIENTS RESPONSIVE TO FIRST-LINE
THERAPY WITH CHLORAMBUCIL AND PREDNISONE
F.R. Mauro, 1 I. Del Giudice, 2 M. Gentile, 2 G. De Angelis, 2
M.S. De Propris, 2 M.E. Ghia, 2 M. Marinelli, 2 L. Quattrocchi, 2
P. Fisinger2 A. Guarini, 2 R. Foà2 1 Division of Hematology, Università La Sapienza, Rome; 2 Division of Hematology
Università La Sapienza, Rome, Italy
Background. Chlorambucil treatment is manageable and well tolerated
in CLL patients, but is associated with partial responses and short
response duration. Aims. With the aim of improving the quality of
response, the anti-CD20 monoclonal antibody Rituximab was given as
post-remissional therapy to older CLL patients (≥60 years) responsive to
first-line treatment with 6 monthly courses of chlorambucil (C: 10
mg/sqm/day, d1-d5) and prednisone (P: 25 mg/sqm/day, d1-d5). Methods.
This study included 19 CLL patients in PR after 6 courses of CP
treatment who received 4 weekly doses of Rituximab (R: 375 mg/m 2 ).
Median age was 65 years (range, 61-81 years). Five patients showed
unmutated IgVH, while 14 were mutated. Prior to starting Rituximab
treatment, the median number and the rate of residual PB CD5/CD20 +
lymphocytes were respectively 638×10 9 /L (range: 129-8134×10 9 /L) and
54% (range: 13-87%) of lymphocytes, while the median rate of residual
BM CD5/CD20 + lymphocytes was 26% (range: 7-55%). Moderately
(≥2cm) enlarged nodes and/or spleen were present in 8 patients (42%).
Clinical and cytometric responses were assessed 4 weeks after the last
Rituximab administration and, thereafter, every 3 months up to disease
progression. Results. After Rituximab, the median number and the rate
of PB CD5/CD19 + lymphocytes decreased to 110×10 9 /L (range: 6-1700
×10 9 /L) and 9% (range: 1-61%) of lymphocytes, respectively, and the
median rate of BM CD5/CD19 + lymphocytes to 5% (range: 0-50%). In
all cases but 2, no enlarged nodes or splenomegaly were observed. Overall,
the reduction of residual disease produced an upgrade of the previous
response from PR to CR in 13 cases (68%), while no significant
changes were documented in 6. Two of the 13 (15%) patients who
achieved a CR after Rituximab showed less than 1% CD5/CD19 + lymphocytes
both in the PB and the BM. No evidence of a clinical benefit
of Rituximab administration was observed in 3/5 IgVH unmutated