title: Low-dose alemtuzumab in refractory/relapsed chronic lymphocytic leukemia: Genetic profile and long-term outcome from a single center experience.
abstract: Relapsed/refractory chronic lymphocytic leukemia (CLL) represents a clinical challenge, in particular when high risk gene mutations occur. In this setting, alemtuzumab was recognized to be effective. This retrospective study evaluates long-term efficacy and tolerability of low-dose alemtuzumab in relapsed/refractory CLL and correlates clinical outcome with biological feature. Sixty-two consecutive patients (median age 68 years) were evaluated; alemtuzumab was administered 30 mg weekly for up to 18 weeks. Among the patients included in the analysis, 37% were fludarabine-refractory, 33.3% carried a TP53 disruption, 14.8% a NOTCH1 mutation and 9% a SF3B1 mutation. Overall response rate (ORR) was 61.3% (complete remission 25.8%). After a median follow-up of 43 months, overall survival (OS) and progression free survival (PFS) were 43.1 and 15 months, respectively; while ORR was 77.8% for patients carrying TP53 disruptions (OS 33.8 months) and 43.5% for fludarabine-refractory patients (OS 30 months). Noteworthy, long-term survivors (OS ≥ 36 months) were 54.8%. None of the biological poor risk factors negatively impacted on ORR, PFS and OS. Grade ≥3 cytopenia occurred in 24.2% patients, 6.5% experienced a grade ≥3 non-CMV infection and no grade ≥3 CMV-event occurred. In conclusion, low dose-alemtuzumab is safe and effective in relapsed/refractory CLL, also in a long-term follow-up and high-risk genetic subgroups.
authors.affiliation: Hematology Unit, IRCCS Ca'granda Ospedale Maggiore Policlinico and University of Milan, via Francesco Sforza, 35, Milan, Italy.
authors.forename: Mariarita
authors.initials: M
authors.lastname: Sciumè
authors.affiliation: Hematology Unit, IRCCS Ca'granda Ospedale Maggiore Policlinico and University of Milan, via Francesco Sforza, 35, Milan, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Vincenti
authors.affiliation: Hematology Unit, IRCCS Ca'granda Ospedale Maggiore Policlinico and University of Milan, via Francesco Sforza, 35, Milan, Italy.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Reda
authors.affiliation: Hematology Unit, IRCCS Ca'granda Ospedale Maggiore Policlinico and University of Milan, via Francesco Sforza, 35, Milan, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Orofino
authors.affiliation: Hematology Unit, IRCCS Ca'granda Ospedale Maggiore Policlinico and University of Milan, via Francesco Sforza, 35, Milan, Italy.
authors.forename: Ramona
authors.initials: R
authors.lastname: Cassin
authors.affiliation: Biostatistics Unit, Regina Elena Institute for Cancer Research and Treatment, via Elio Chianesi, 53, Rome, Italy.
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.affiliation: Division of Hematology, Dept. Of Translational Medicine, A. Avogadro University of Eastern Piedmont, Corso, Mazzini, 18, Novara, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Gaidano
authors.affiliation: Division of Hematology, Dept. Of Translational Medicine, A. Avogadro University of Eastern Piedmont, Corso, Mazzini, 18, Novara, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Hematology Unit, IRCCS Ca'granda Ospedale Maggiore Policlinico and University of Milan, via Francesco Sforza, 35, Milan, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Cortelezzi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D015870:Gene Expression; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1 / Q000235:genetics; D012008:Recurrence; D012074:Remission Induction; D012189:Retrospective Studies; D017413:Ribonucleoprotein, U2 Small Nuclear / Q000235:genetics; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; C497761:NOTCH1 protein, human; D010750:Phosphoproteins; D000072260:RNA Splicing Factors; D051881:Receptor, Notch1; D017413:Ribonucleoprotein, U2 Small Nuclear; C112491:SF3B1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000074323:Alemtuzumab; D014740:Vidarabine; C024352:fludarabine