LWBK1006-32 LWW-Govindan-Review November 24, 2011 11:28
456 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Reviewvarious clinical trials including fludarabine in combination with other
agents, CR and overall response rates have been superior with the combi-
nation arm. However, because of the usually long duration of disease that
most patients experience, no trials have consistently demonstrated supe-
rior overall survival rates with one chemotherapy regimen over another.
In the CALGB 9712 trial of sequential fludarabine and rituximab versus
concurrent therapy, there was a significant increase in the CR rate, but
there was also an increase in the incidence of grade 3 and 4 neutropenia.
The combination of fludarabine, cyclophosphamide, and rituximab has
been evaluated in both treatment-na ̈ıve and previously treated patients.
In treatment-na ̈ıve patients, a CR rate of 70% was observed with a pro-
jected failure-free survival at 4 years of 69%; this is the highest response
rate reported for any regimen for previously untreated patients in CLL.
Unfortunately, patients carrying deletions in 17p or 11q have repeatedly
demonstrated inferior outcomes with respect to progression-free survival
in these studies.Answer 32.11. The answer is D.
Alemtuzumab is a humanized monoclonal antibody targeting CD52,
which is highly expressed on CLL cells in addition to normal B and T lym-
phocytes. In a pivotal study of patients who were previously treated with
fludarabine, second-line therapy with alemtuzumab was able to induce
a CR in 2% of patients and a PR in 31% of patients. Some 59% of
patients achieved stable disease as well. This led to the FDA approval of
single-agent alemtuzumab for patients with fludarabine-refractory CLL.
Alemtuzumab is effective at treatment of marrow and peripheral blood
disease; however, it is less effective at treating patients with bulky lym-
phadenopathy. Of note, this agent is associated with an increased risk
of cytomegalovirus infections and is also effective in patients with 17p
deletion, which has generally been resistant to therapy with other agents.
Another monoclonal antibody, rituximab, directed against CD20 on
malignant and normal B cells, has very limited activity as a single agent
in CLL. This is likely because CLL cells demonstrate relatively low levels
of expression of CD20 compared with normal lymphocytes, as well as
the demonstration of increased levels of soluble CD20 in patients with
CLL, which may interfere with rituximab’s ability to induce antibody-
dependent cellular cytotoxicity on target cells. Because this patient has
progressed on combination therapy with fludarabine and cyclophos-
phamide, continuation with this regimen with addition of rituximab is
unlikely to be of much clinical benefit.Answer 32.12. The answer is A.
The most common clonal cytogenetic abnormalities in patients with
CML, in addition to t(9;22), which are found at diagnosis include dupli-
cation of the Philadelphia chromosome, trisomy 8, iso-17q, and trisomy- Although iso-17q has been associated with a poorer prognosis, the
prognostic significance of the other chromosomal abnormalities is less
clear.