Conference Correspondent

Chlorambucil plus Rituximab as Front-Line Therapy for Elderly and/or Unfit CLL Patients. Long-Term Follow-Up and Correlation with Biologic-Based Risk Stratification

Conference Correspondent 

Elderly patients with chronic lymphocytic leukemia (CLL) and younger patients with comorbidities are often treated with chlorambucil (Chl) despite the relatively low response rates. The addition of anti-CD20 monoclonal antibodies to Chl substantially increases the response rates, without negatively affecting tolerability. Overall response rates (ORRs) between 66% and 84% have been reported with these combinations, with complete responses (CRs) ranging from 8% to 26%.1 Laurenti and colleagues reported results from a retrospective analysis on the use of the Chl-rituximab (R) combination as frontline treatment for elderly (≥65 years) and/or unfit (CIRS >6) CLL patients treated at 15 different Italian hematologic centers. The main aim of the study was to further establish the safety and efficacy of the Chl-R protocol and investigate whether certain CLL patients for whom this protocol is particularly effective could be identified. To this end, a subgroup analysis was performed stratifying patients according to FISH and IGHV results: the high-risk group included patients with del17p, the intermediate-risk group (IR) included patients with del11q and/or unmutated IGHV, and the low-risk group (LR) comprised patients without del11q or del17p and/or unmutated IGHV. A total of 102 patients who underwent treatment were enrolled in the study. The median number of Chl and R cycles administered in the 102 patients was 8 (range, 2-12) and 6 (range, 1-9), respectively. The planned treatment schedule was different among centers: the 2 main schedules used were Chl administered at 1 mg/kg for each cycle every 28 days, given at a fixed daily dose of 10 mg starting from day 1 and repeated for 8 cycles, and Chl administered at 8 mg/m2/day for 7 days of each of eight 28-day cycles. R was added to Chl from the third cycle onward and was administered on day 1 of each cycle at a dose of 375 mg/m2 during the first administration and 500 mg/m2 for the subsequent 5 cycles.

On an intent-to-treat basis, the ORR was 87.1%. Thirty-two (31.7%) patients attained a CR and 56 (55.4%) patients attained a partial response. No statistically significant differences were noted in terms of ORR for age above or below 70 years, fitness status, Eastern Cooperative Oncology Group, bulky disease, cytogenetic risk abnormalities, IGHV mutational status, ZAP-70, or CD38 expression. Median progression-free survival (PFS) and time to retreatment were reached at 43.7 months and 72.3 months, respectively. Median overall survival was not reached; 86.1% and 81.2% of patients were alive at 48 months and 60 months, respectively. The most frequent serious adverse event was grade 3-4 neutropenia, occurring in 13.7% of patients. Grade 3-4 extra-hematologic side effects were uncommon (9.8%). Subgroup analysis of the LR and IR patients showed that LR patients had a significantly better PFS than IR patients (65.8 months vs 35.2 months, P=0.001), with 54.9% of patients remaining free from disease progression 60 months after treatment.

The authors concluded that treatment of elderly and/or unfit CLL patients with the Chl-R regimen is associated with low toxicity, a high ORR, and durable PFS. Particularly good results were achieved in CLL patients with a mutated IGHV profile and not carrying del17p and del11q, suggesting that in this low-risk subset of unfit patients, Chl-R could represent the optimal therapeutic option taking into consideration safety, efficacy, and cost.

Laurenti L, et al. ASH 2016. Abstract 3240.

  1. Lepretre S, et al. Leuk Lymphoma. 2016;57:852-865.

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