Rituximab/Alemtuzumab May Be Beneficial for Poor-Prognosis Patients With Chronic Lymphoid Malignancies

HOUSTON-Both rituximab(Rituxan), an anti-CD20 monoclonalantibody, and alemtuzumab (Campath-1H), an anti-CD52 monoclonalantibody, are effective in the treatmentof relapsed/refractory chroniclymphocytic leukemia (CLL). The responsein some anatomic disease sites,however, such as lymph nodes andbone marrow, is unsatisfactory andneither antibody alone is curative.In relapsed/refractory CLL, responserates to single-agent alemtuzumabare typically 33% to 53%.[1-3]The combination of alemtuzumabwith rituximab, however, yields higherresponse rates than alemtuzumabalone in patients with relapsed/refractoryCLL, according to results presentedby Stefan Faderl, MD, andcolleagues from The University ofTexas M.D. Anderson Cancer Centerin Houston (ASH abstract 775).[4]Re-treatment OptionThe study involved a heterogeneousgroup of poor-prognosis patientswith CLL and other chroniclymphoid malignancies that coexpressthe CD20 and CD52 antigens.Rituximab was given at 375 mg/m²intravenously weekly for four dosesand alemtuzumab administered at 3,10, and 30 mg intravenously on days1 through 3 for week 1 and 30 mgthereafter on days 3 and 5 for weeks 2through 4.Patients also received prophylactictrimethoprim-sulfamethoxazoleand valacyclovir (Valtrex) duringtherapy. They were tested weekly forcytomegalovirus antigens in theblood. The protocol allowed theoption of re-treatment with alemtuzumaband rituximab for up to threecourses.A total of 48 patients with a medianage of 62 years (range, 44 to 79years) and a median of four priortherapies (range, one to nine priortherapies) were enrolled. Most (79%)patients had Rai stage 3 or greaterdisease and 54% had failed prior fludarabine(Fludara) therapy, with orwithout an alkylator. The majority,32 patients, had CLL; 1 patient hadprolymphocytic leukemia (PLL); 9had CLL/PLL; 4 had mantle cell leukemia;and 2 had Richter's transformation.Responses Exceed 50%Among the 48 patients evaluablefor response, 25 (52%) achieved abeneficial response. Complete responseoccurred in 8% of patients,nodular partial response in 4%, andpartial response in 40% of patients.Among 32 patients with CLL, 20 (63%)responded, including two completeresponses (CR) and one nodular partialresponse. No responses were observedin patients with mantle cellleukemia or Richter's.Of the 25 patients who responded,90% had a complete response inblood, 37% had a complete responsein bone marrow, 59% had improvementof at least 50% in lymph nodes,and 67% had at least 50% improvementin liver/spleen. Dr. Faderl suggestedthat these response rates werenoteworthy and appeared to be higherthan those seen with single-agentalemtuzumab, especially as almost allof these responses were acheived afteronly 4 weeks of therapy.The combination of alemtuzumaband rituximab was well tolerated.Most nonhematologic adverse eventswere infusion related and less than orequal to grade 2 by National CancerInstitute Common Toxicity Criteria.The most commonly reported adverseevents included fever in 36 patients(75%), rigors in 32 (67%), skinreactions in 18 (38%), fatigue in 16(33%), gastrointestinal symptoms in13 (27%), and dyspnea in 12 (25%).Among the 48 patients in the study,infectious episodes occurred in 25 patients(52%). These episodes includedcytomegalovirus reactivation in 13patients (27%), which was symptomaticin 7 (15%), fever of unknownorigin in 6 patients (13%), pneumoniain 5 patients (10%), and sinusitisin 3 patients (6%).These results, said Dr. Faderl, showthat combination therapy with alemtuzumaband rituximab is feasible andthat response rates appear to be improvedrelative to those observed withalemtuzumab alone. Given the poorprognosis of this patient population,the responses seen with this new combinationtherapy may provide an importantcontribution for further developmentof monoclonal antibodytherapy.

References:

1.

Rai KR, Freter CE, Mercier RJ, etal: Alemtuzumab in previously treatedchronic lymphocytic leukemia patientswho also had received fludarabine.J Clin Oncol 20:3891-3897, 2002.

2.

McCune SL, Gockerman JP,Moore JO, et al: Alemtuzumab inrelapsed or refractory chronic lymphocyticleukemia and prolymphocyticleukemia. Leuk Lymphoma43:1007-1011, 2002.

3.

Keating MJ, Flinn I, Jain V, et al:Therapeutic role of alemtuzumab(Campath-1H) in patients who havefailed fludarabine: results of a largeinternational study. Blood 99:3554-3561, 2002.

4.

Faderl S, Thomas DA, O’BrienS, et al: Combined use of alemtuzumaband rituximab in patients with relapsedand refractory chronic lymphoidmalignancies-An update ofthe M.D. Anderson experience (abstract775). Blood 100:206a, 2002.