NEW ORLEANSChronic lymphocytic leukemia (CLL) and small
lymphocytic lymphoma (SLL) may benefit from treatment with monoclonal
antibody treatments directed against the CD20 and/or CD52 antigens,
according to data presented at the ASH meeting. Increasing dosing
frequency of rituximab (Rituxan) to three times per week produced
responses in half of CLL/SLL patients treated in a phase I/II trial
reported by John C. Byrd, MD, of the Hematology-Oncology Service at
Walter Reed Army Medical Center, Washington, DC. In a separate study
at M.D. Anderson Cancer Center in Houston, one-third of patients with
CLL refractory to fludarabine (Fludara) responded to the anti-CD52
monoclonal antibody Campath-1H.
Thrice Weekly Rituximab
Giving rituximab at an accelerated, three-times-per-week schedule
produces responses in half of patients with CLL or SLL, including
some complete responses, Dr. Byrd reported (see
Table 1). Although rituximab had demonstrated significant
activity in low-grade non-Hodgkins lymphoma (NHL), it was less
effective in SLL, a nodal variant of CLL. The SLL patients had
relatively low serum rituximab trough levels on the standard weekly
dosing regimen. To address the possibility that the lower response
rate was due to inadequate rituximab dose levels, Dr. Byrd initiated
the thrice-weekly schedule.
The study included 33 patients, 26 with CLL and 7 with SLL. Patients
had a median of two prior therapies. According to Rai criteria, 8
patients had intermediate-risk disease, and 25 had high-risk disease.
All had CD20 expression.
Rituximab was given on day 1 at a 100 mg dose over 4 hours to
minimize infusion-related events. Patients then received rituximab at
250 mg/m² or 375 mg/m² on day 3 and then three times per
week at that dose for 4 weeks for a total of 12 treatments. Patients
also received diphenhydramine HCl (Benadryl), acetaminophen
(Tylenol), and allopurinol (Allopurinol, Oxipurinol, and others) to
minimize infusion-related side effects. If infusion-related events
occurred, the infusion was stopped, symptoms treated, and the
infusion resumed after symptoms had resolved.
One patient had treatment discontinued due to infusion effects.
Twenty had infusion reactions on day 1, and 12 had infusion events on
day 3. Six patients had platelet levels of 20,000-50,000
cells/mm³. Half of these patients had platelets drop to under
20,000 cells/mm³ after the first rituximab infusion, but these
later returned to baseline levels. Dr. Byrd reported that there was
no correlation between lymphocyte counts and infusion-related events.
Six patients had serious adverse events. One died of pulmonary
hemorrhage, which Dr. Byrd said was possibly drug-related, and five
The overall response rate was 44%, Dr. Byrd reported.
Response was 100% in patients who had not been previously treated.
Rituximab has significant clinical activity in CLL, Dr.
Byrd commented. Patients who responded to rituximab had hematologic
improvement and a decrease in lymphadenopathy. The durability of
these responses is uncertain, since median follow-up was only 6
months at the time of this report.
Based on these results, Dr. Byrd advised using the three-times-weekly
schedule for rituximab in CLL/SLL and using the stepped-up dosing
schedule to minimize infusion reactions.
Anti-CD52 Antibody Michael J. Keating, MD, on behalf of the
International Campath study group, reported preliminary data from a
phase II study of the anti-CD52 antibody Campath-1H. In previous
trials, Campath-1H produced high response rates in patients with
B-cell CLL who were treatment-naïve, but was less effective in
previously treated patients. The new study looked at 93 patients with
B-cell CLL previously treated with alkylating agents and refractory
This is a group with an extremely poor prognosis, Dr.
Keating pointed out. All patients either had no response to previous
chemotherapy or had relapsed within 6 months or less after a
In 93 patients evaluable for response, Dr. Keating reported:
2 (2%) achieved complete response (CR).
29 (31%) had partial response (PR).
55 (59%) had stable disease.
4 (4%) had progressive disease.
3 (3%) with uncertain responses, which were assumed to be treatment failures.
Toxicity a Problem
Even though many patients had stable disease by the study
criteria, most had cleared peripheral blood and reduction of
lymphadenopathy, Dr. Keating said. They were classified
as stable disease because of insufficient recovery of platelets or
shrinkage of lymph nodes.
Patients who were Rai stage IV did less well and patients over age 70
had a low response rate which was not statistically significant, Dr.
Keating added. Response rates were associated with the size of
involved nodes (see Table 2).
At a median follow-up of more than 5 months, the two patients in CR
were still in remission and estimated median survival was 12+ months.
Toxicity was a problem, however. Mortality due to infection was 5%,
including 3% fatal sepsis and 2% fatal pneumonia. Almost all
patients have some sort of side effects during the first 3
infusions, Dr. Keating said. These included grade 3-4 rigors,
fever, dyspnea, or fatigue in 10% to 20%.
The risk of infection decreased with time, and Dr. Keating speculated
that it may be correlated with CD4 cell counts. Campath-1H is
very active in advanced refractory patients with CLL. The toxicity
profile is acceptable in such a patient population, Dr. Keating concluded.