Fludarabine, cyclophosphamide, and rituximab chemoimmunotherapy is highly effective treatment for relapsed patients with CLL

Abstract

Optimal management of patients with relapsed/refractory chronic lymphocytic leukemia (CLL) is dictated by patient characteristics, prior therapy, and response to prior therapy. We report the final analysis of combined fludarabine, cyclophosphamide, and rituximab (FCR) for previously treated patients with CLL and identify patients who benefit most from this therapy. We explore efficacy of FCR in patients beyond first relapse, patients with prior exposure to fludarabine and alkylating agent combinations, and patients with prior exposure to rituximab. The FCR regimen was administered to 284 previously treated patients with CLL. Patients were assessed for response and progression by 1996 National Cancer Institute-Working Group (NCI-WG) criteria for CLL and followed for survival. The overall response rate was 74%, with 30% complete remission. The estimated median overall survival was 47 months and median progression-free survival for all patients was 21 months. Subgroup analyses indicated that the following patients were most suitable for FCR treatment: patients with up to 3 prior treatments, fludarabine-sensitive patients irrespective of prior rituximab exposure, and patients without chromosome 17 abnormalities. FCR is an active and well-tolerated therapy for patients with relapsed CLL. The addition of rituximab to FC improved quality and durability of response in this patient population. (Blood. 2011;117(11): 3016-3024)

Proliferation centers in chronic lymphocytic leukemia: correlation with cytogenetic and clinicobiological features in consecutive patients analyzed on tissue microarrays

“…While the latter features did not have prognostic predictivity at multivariate analysis in this clinically aggressive population, our study demonstrated that the histopathological pattern defined by the presence of confluent PCs may represent an important feature for risk assessment in this subset of patients. This finding is important when considering that increasing awareness of the possible evolution into Richter's syndrome is prompting clinicians to perform lymph node biopsy more often than in the past, 45 and that the therapeutic armamentarium in clinically aggressive CLL may include intensive chemoimmunotherapy 46 and allogeneic bone marrow transplantation from HLA-identical siblings and well-matched unrelated donors. 47,48 …”

Bendamustine and subcutaneous alemtuzumab combination is an effective treatment in relapsed/refractory chronic lymphocytic leukemia patients

“…Responses in patients with 17pdel/TP53 mutation were consistent (57%), comparing favorably to regimens including anti-CD20 monoclonal antibody therapy either with FC (35%) 12 or B (rituximab 7.1%, ofatumumab 37%).…”

“…In the MD Anderson Cancer Center experience responses after FCR were affected by the type of previous treatment. 12 As mentioned above, number and quality of responses were unaffected by previous type and number of lines of therapy, although 38% patients had previously received FCR. Furthermore, after BenCam, compared to FCR we recorded similar responses in 11q del cases and confirmed the favorable impact of alemtuzumab combining treatment in patients showing trisomy 12.…”

The Treatment of Relapsed Refractory Chronic Lymphocytic Leukemia

“…However, a recent report of 284 relapsed patients treated with FCR that did consider refractory patients separately found that those who were fludarabine refractory had a complete remission (CR)/nodular partial remission (nPR) rate of only 8% (ORR 56%), compared with 46% for other patients previously exposed to fludarabine and alkylators. 10 In multivariable analysis, fludarabinerefractory disease was a significant predictor of short PFS and OS, along with 17p deletion and complex karyotype, among others, 10 leading the investigators to conclude that FCR is most appropriate for fludarabine-sensitive patients with up to 3 prior regimens and without 17p abnormalities. Other regimens with described activity in fludarabine-refractory CLL include CFAR (FCR plus alemtuzumab) and OFAR (oxaliplatin, fludarabine, cytarabine, rituximab), but results are not clearly better than FCR in this group (Table 1).…”