Prospective, Observational Study To Assess The Safety Of Rituximab In Combination With Chemotherapy In Patients With Previously-Untreated Or Relapsed Or Refractory B Cell-Lineage Chronic Lymphocytic Leukaemia (B-CLL): Preliminary Results

The efficacy and safety of rituximab plus chemo (R+chemo) for first-line and relapsed B-CLL patients(pts) have been widely investigated in clinical trials and large patient cohorts, but much less is known about whether such regimens can be effectively and safely administered to unselected pts in the community setting to reflect the routine care of B-CLL pts. Therefore, this observational study was designed to characterize the type, severity and frequency of all adverse events occurring on-treatment and in the year following rituximab infusion. A secondary objective was to assess response rate (CR/nPR/PR), duration of response, disease-free survival, overall survival, and to evaluate the relationship between various baseline markers and clinical outcome parameters in a subset of pts in each study group.

Data were collected prospectively from B-CLL pts, in 47 Spanish hospitals, commencing a new treatment with prescribed R+chemo in accordance with normal clinical practice at the time of enrollment. Data cut-off for this interim analysis was May 31, 2013.

A total of 218 pts have been enrolled, 108 and 110 pts in the first-line and relapsed arm, respectively. The median age (range) of the whole series was 69 (r: 29–87) years. ECOG status varied across the two groups, with a 1 ECOG status score of 23%, and 55% of first-line and relapsed pts, respectively. In the first-line arm, 26%, 47%, and 27%, had a Binet stage of A, B and C, respectively. In the relapsed arm, 11%, 42%, and 46% had a Binet stage of A, B and C, respectively. By first-line / relapsed arm, the proportion of pts with del(11q), del(17p), and unmutated IgVH) was: 14%/15%; 17%/10%; and 10%/9%, respectively. Treated pts were categorized as receiving fludarabine/cyclophosphamide/rituximab (FCR) 60%/20%, bendamustine/rituximbab (BR) 15%/42%, chlorambucil/rituximbab (ClbR) 12%/19%, or other R-based therapy 13%/20%, in the first-line and relapsed arm, respectively.

The overall response rate (ORR) in the first-line arm was as follows: BR cohort (81%; 13/16), ClbR (69%; 9/13) and FCR cohort (68%; 44/65), while in the relapsed group the ORR was higher in the ClbR cohort (55%; 11/20), followed by other R-based (48%; 10/21) and FCR cohort (43%; 9/21).

Adverse events were most frequently hematologic and infusion-related and included nuetropenia (34% first-line; 28% relapsed); fever (19%; 12%); nausea (14%; 11%); lymphopenia (12%; 9%), and vomiting (11%; 8%). CTC grade 3-5 adverse events occurred in 55% of all 218 pts. Grade3 and 4 neutropenia occurred in 23% (FCR), 25%(BR) and 15% (ClbR) of first-line pts. In the relapsed group this incidence was of 14% (FCR), 16% (BR), and 25% (ClbR). The reported incidence of CTC grade 3 or 4 febtrile neutropenia (FN) in the first-line FCR, and BR cohort was of 9%, and 6%, respectively, while pts in the relapsed group the incidence of grade 3-4 FN was of 19% for FCR and 16% for BR. No FN was reported in the ClbR cohort, on both arms. Infection was reported in 61% and 17% of pts in the first-line/relapsed CFR cohort; 13% and 50% in the first-line/relapsed BR cohort, and 16% and 12% in the first-line/relapsed ClbR cohort, respectively.

Treatment discontinuations due to AEs in the first-line and relapsed arm was of 12% and 9%, while treatment related mortality occurred in 3% and 4%, respectively.

In this unselected group of B-CLL patients taken from normal clinical practice, in first-line, or relapsed approach, rituximab seems an effective and relatively safe option when added to any chemotherapy regimen. Additional analysis of the whole study will give us further information on late toxicity and outcome.

Garcia Bernaldez:Roche Pharma: Employment. Gonzalez-Grande:Roche Pharma: Employment.