COLOGNE, Germany—Combining rituximab(Drug information on rituximab) (Rituxan) with fludarabine (Fludara) is a feasible, effective strategy in treating chronic lymphocytic leukemia (CLL), as it produces a 90% response rate and does not increase infection risk beyond that seen with fludarabine alone, Holger Schulz, MD, reported in a poster presentation at the 43rd Annual Meeting of the American Society of Hematology. Dr. Schulz is in the Department of Hematology/Oncology at the University of Cologne, Germany.
Rationale and Study Design
"Fludarabine is generally considered standard first-line therapy for CLL, producing response rates up to 71%. However, most of these patients will relapse, and a significant proportion of CLL patients will not respond to fludarabine at all," Dr. Schulz said. "The rationale for combining rituximab with fludarabine includes single-agent efficacy of both drugs, possible synergism of rituximab and chemotherapy, and no apparent overlapping toxicities."
The report included 29 patients treated with fludarabine at 25 mg/m²/d (on days 1-5, 29-33, 57-61, 85-89). The first two infusions of rituximab were given together with fludarabine on days 57 and 85, while the following doses (375 mg/m²) were given on days 113 and 151. Eighteen patients were previously untreated, and 11 had previous chlorambucil(Drug information on chlorambucil)/prednisone. Twenty-one patients had stage B disease, and 8 had stage C.
The overall response rate in 29 evaluable patients was 90% (see Table 1), including 7 complete responses (24%), 3 unconfirmed complete responses (10%), and 16 partial responses (53%). In previously untreated patients, 16 of 18 responded (89%). The median time to progression has not been reached after a median follow-up of 6 months.
Toxicity Is Tolerable
Grade 3 or 4 adverse events included infections in four patients (13%) and fever in one (3%). The most common side effects—fever, chills, and exanthema of the skin—were mild. Fever and chills were mainly related to the first rituximab infusion. Hematologic toxicity included neutropenia grade 1/2 in 30%, grade 3/4 in 37% and thrombocytopenia grade 1/2 in 20%, grade 3/4 in 10%. Dr. Schulz told Oncology News International that the neutropenias typically resolved in 3 to 4 days without intervention. One patient died after the second cycle of fludarabine during prolonged thrombocytopenia due to cerebral bleeding. No hemolytic anemia has been noted.
