A phase II study of fludarabine (F), cyclophosphamide (C), and mitoxantrone (M) plus rituximab (R) (FCM-R) in previously untreated patients (pts) with CLL ≤ 70 years (yrs)

6607 Background: Rituximab plus chemotherapy has demonstrated higher and better quality responses (MRD-negative) than chemotherapy alone. FCR produced overall response rates of 95% and complete remissions in 73%. Responses were lower in pts ≥ 70 years and β2M levels > 2 × ULN, and myelosuppression-associated complications were more frequent. High response rates of 60% and 88% have been reported with FCM in pts with relapsed and untreated CLL. We here report results of FCM plus rituximab and pegfilgrastim in patients ≤ 70 yrs. with previously untreated CLL. Methods: Pts ≤ 70 yrs with untreated, symptomatic CLL (NCI-WG criteria) were eligible. Pts were excluded for β2M > 2 × ULN and ECOG PS > 2. For course 1, doses of fludarabine were 25 mg/m2 i.v. daily d2–4, cyclophosphamide 250 mg/m2 i.v. daily d2–4, mitoxantrone 6 mg/m2 i.v. d2, and rituximab 375 mg/m2 i.v. d1. Pegfilgrastim was 6 mg s.c. on d4. Courses were repeated q4–6 wks. For courses 2–6, FCM started day 1 with rituximab 500 mg/m2. Study endpoints included evaluation of efficacy (clinical and 2-color flow [CD5/CD19] response rate after 3 and 6 cycles) and toxicity. Results: Twenty-three pts have been treated, 19 are evaluable for response after 3 and 11 pts after 6 cycles. Median age: 57 yrs (38–69). Twelve pts (52%) were male. Rai stage ≥ 3 was present in 17%. Median β2M was 2.7 mg/dL (1.4–4) and median WBC 59.9 × 109/L (5.6–355). Unfavorable FISH abnormalities were present in 3/17 (18%), unmutated IgVH in 9/12 (75%), and ZAP-70 immunohistochemistry was positive in 10/14 (71%) pts. After 3 cycles, all 19 pts responded (4 [21%] CR, 5 [26%] nPR, 10 [53%] PR). Six pts (32%) had <1% CD5/CD19-positive cells in the marrow. Response rates after 6 cycles: 2 (18%) CR, 1 (9%) nPR), 8 (73%) PR (PR due only to failure to recover counts in 7 pts) for an OR rate of 100%. Six pts (55%) had < 1% CD5/CD19-positive marrow cells at 6 months. Only 2 pts stopped prematurely because of persistent neutropenia. Conclusions: FCM-R achieves high clinical response rates. The frequency of pts with flow cytometry response < 1% CD5/CD19-positive cells was similar to FCR. Myelosuppression-related complications were infrequent. Use of hematopoietic growth factors with chemoimmunotherapy regimens is recommended. [Table: see text]