Rituximab, Fludarabine, Cyclophosphamide, and Mitoxantrone: A New, Highly Active Chemoimmunotherapy Regimen for Chronic Lymphocytic Leukemia

Abstract

R-FCM is highly effective in previously untreated CLL, with an 82% CR rate and a high proportion of MRD-negative CRs (46%). Treatment toxicity is acceptable. Parameters correlating with a lower response rate were advanced clinical stage, high serum beta2-microglobulin levels, and del(17p). Based on these results, R-FCM warrants further investigation in randomized clinical trials.

The prognostic impact of minimal residual disease in patients with chronic lymphocytic leukemia requiring first-line therapy

“…These patients are considered to have achieved a minimal residual disease (MRD) negative status. [17][18][19][20] Several phase II trials have demonstrated that patients achieving MRD negativity have a significantly longer survival than those who remain MRD positive, and this is true for patients treated with conventional chemotherapy, 21,22 monoclonal antibodies, 23 chemoimmunotherapy, 24 or stem cell transplantation. 25,26 Furthermore, a phase III trial performed by the German CLL Study Group (GCLLSG) recently revealed that patients obtaining MRD negativity had significantly longer progression-free and overall survivals, irrespectively of the treatment received.…”

Current strategies for the diagnosis and management of chronic lymphocytic leukemia (CLL), with a focus on poor-risk CLL: A review

“…The LRF CLL4 trial that included 777 CLL patients that required treatment reported that patients with del 17p had significantly poorer response to fludarabinebased treatment and shorter PFS [28]. In a Spanish trial del 17p was associated with a significantly lower CR rate [33], and in the GCLLSG CLL4 (F vs. FC) and CLL8 trials (FC vs. FCR) del 17p was associated with dramatically lower CR, OR, OS, and PFS [31].…”

“…For example, Bosch et al conducted a phase II trial with 29 previously untreated CLL patients receiving rituximab plus FCM (mitoxantrone), followed by rituximab maintenance every 3 months for up to 2 years [33]. The OR, MRD-(minimal residual disease) negative CR, MRD-positive CR, and PR rates were 93%, 46%, 36%, and 11%, respectively, proving the efficacy of the regimen.…”

Changing paradigms in the treatment of chronic lymphocytic leukemia

“…In one study of 72 previously untreated patients, mitoxantrone at 6 mg/m 2 was added to FCR on day 1 of each cycle (R-FCM) with an ORR of 93%, an MRD-negative CR rate of 46%, an MRD-positive CR rate of 36% and a PR rate of 10%. 58 Major infections were reported in 8% of cycles. In another study, 30 previously untreated patients received FCR with 6 mg/m 2 of mitoxantrone (FCM-R) on day 2 of each cycle.…”

“…Phase 2 data suggests that adding additional agents such as mitoxantrone to FCR does not increase efficacy. [58][59][60] If BR, PCR or FCR-Lite have equal efficacy and less toxicity than FCR then they might be preferable front-line treatments; however, currently there is no phase 3 data to support this. Phase 2 data suggests that both FCR-Lite 55 and PCR 59 have considerably less grade 3/4 neutropenia than FCR.…”