An open-label, pilot study of fludarabine, cyclophosphamide, and alemtuzumab (FCC) in relapsed/refractory patients with B-cell CLL

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BlankAn open-label, pilot study of fludarabine, cyclophosphamide, and

alemtuzumab (FCC) in relapsed/refractory patients with B-cell chronic

lymphocytic leukemia.

M Montillo, A Tedeschi, VB Petrizzi, F Ricci, M Crugnola, M Spriano, P Spedini,

F Ilariucci, L Uziel, I Attolico, E Vismara, A De Blasio, A Zaccaria, and E

Morra

Blood, July 19, 2011; .

Department of Oncology/Haematology, Niguarda Ca' Granda Hospital, Milano, Italy;

Although combination regimens have improved outcomes over monotherapy in chronic

lymphocytic leukemia (CLL), patients eventually relapse. Combined fludarabine,

cyclophosphamide, and monoclonal anti-CD52 antibody alemtuzumab (FCC) provided

synergistic cytotoxicity with effective clearing of minimal residual disease.

This phase 2 study determined FCC efficacy and safety in relapsed/refractory

CD52-positive B-CLL following ?1 line of treatment. From January 2005 through

June 2008, up to six courses of oral fludarabine 40 mg/m(2)/d, oral

cyclophosphamide 250 mg/m(2)/d, and subcutaneous alemtuzumab (Mab-Campath(?)) 10

mg (increased to 20 mg after first 10-patient cohort) were administered days 1

to 3 every 28 days. The primary objective was overall response rate (ORR);

secondary objectives included response duration, time to disease progression,

and safety and tolerability. ORR was 67% in 43 patients; 30% achieved complete

response (CR). ORR significantly improved with one versus ? two prior therapies

(P=.018), and without versus with previous monoclonal antibody treatment

(P=.003). Median progression-free survival was 24.4 months, not reached in

patients achieving CR. Median overall survival was 33.6 months. Myelosuppression

was the most common adverse event, with a low percentage of cytomegalovirus

reactivations and manageable infections. However, a close vigilance of

opportunistic infections is warranted. FCC provides effective immunotherapy in

relapsed/refractory CLL, including in patients with poor-risk prognostic

factors.

PMID: 21772050