Chemo/Rituximab Is Effective as First-Line CLL Therapy

December 1, 2002

LUGANO, Switzerland-Thechemotherapy/immunotherapy regimenFCR (fludarabine, cyclophosphamide,rituximab) has produced thehighest complete response (CR) rateseen thus far in first-line treatment ofchronic lymphocytic leukemia (CLL),according to investigator Michael J.Keating, MD. The FCR regimen,which is well tolerated, also results inmolecular remissions in a "significantnumber" of complete responders, saidDr. Keating, professor of medicine,M.D. Anderson Cancer Center.

LUGANO, Switzerland-Thechemotherapy/immunotherapy regimenFCR (fludarabine, cyclophosphamide,rituximab) has produced thehighest complete response (CR) rateseen thus far in first-line treatment ofchronic lymphocytic leukemia (CLL),according to investigator Michael J.Keating, MD. The FCR regimen,which is well tolerated, also results inmolecular remissions in a "significantnumber" of complete responders, saidDr. Keating, professor of medicine,M.D. Anderson Cancer Center."I think we now have an outpatientregimen that can accomplishPCR [polymerase chain reaction]negativity to a level that was formerlyonly achievable with varioustransplant procedures," Dr. Keatingsaid. "It will be intriguing to followthese patients and see how durablethese responses are."The study, which included 135 patientswith CLL who received six cyclesof FCR, achieved a complete responserate of 67% (90 patients), Dr.Keating reported at the 8th InternationalConference on MalignantLymphoma (ICML abstract 008). Bycomparison, front-line fludarabine(Fludara), in previous investigations,has resulted in a 35% complete remissionrate, while adding cyclophosphamideto fludarabine increases theCR rate to 43%.The FCR regimen is an infusionof rituximab (Rituxan) at a conventionaldose (375 mg/m2) on the firstday of the first cycle, with fludarabineand cyclophosphamide given on days2, 3, and 4. In subsequent cycles,rituximab is given at a higher dose(500 mg/m2) on day 1, along withthe 3-day fludarabine/cyclophosphamidecouplet. Cycles are repeated every4 weeks for a total of six cycles.The median patient age was 57years, or somewhat lower than inprevious studies of first-line treatmentfor CLL. Dr. Keating attributesthis to the "Internet phenomenon"-younger patients seeking outmore aggressive therapies.The treatment was well tolerated,with 74% of patients completingsix cycles, and only 4% completingless than three cycles.Overall Response Rate
The overall response rate was95%, including 67% complete remissions,14% nodular partial remissions,and 14% partial remissions.Early death occurred in 2patients (1%). "Although this is avery aggressive approach, the earlydeath rate was actually quite low,"Dr. Keating said. With a median follow-up of 27 months, 125 of the135 patients are still alive.INDUSTRY WATCHPhase II Trial of ISF154 for Treatment of CLL
SAN DIEGO-Tragen Pharmaceuticals has initiated a phase II clinicaltrial of its lead product, ISF154, in the treatment of patients with chroniclymphocytic leukemia (CLL). ISF154 is designed to activate dormantleukemia B-cells and rally T-cells to attack blood- and tissue-basedleukemia cells, the company said in a press release.Investigators will administer ISF-154 to 40 patients in two cohorts: 20patients who have failed chemotherapy will receive up to 10 doses ofISF154 over 20 weeks; 20 patients with advanced disease who havedeclined chemotherapy will receive up to 10 doses of ISF154 asfrontline therapy.Complete response rate did notvary much according to Rai stage(69% for stage 0-II and 52% for stageIII-IV). However, the CR rate was66% for patients under 70 years ofage vs 33% for patients over 70, andlow beta-2-microglobulin levelswere a "very powerful predictive factor"in favor of complete response.Molecular remission (as shownby PCR negativity for IgH) was seenin 58% of complete responders tested(33 of 57 patients). Of 26 patientstested again after 6 months,18 (69%) remained negative, and 5of 6 patients tested again at 12months remained negative.Toxicity associated withrituximab infusion included feverand chills with the first dose for 45patients; a few patients had hypotension,nausea, or dyspnea, althoughall of these toxicities were uncommonin later cycles. Hematologic toxicitiesincluded neutropenia (31% ofcycles) and grade 3-4 thrombocytopenia(6% of cycles). Major infectionsoccurred in 2% of cycles.