ALBERT

Description: Abstract 2724 Background: The NHL 1 study, a prospective, multicenter, randomized, phase 3 study which compared B-R and CHOP-R as first-line treatment in indolent lymphomas and mantle cell lymphoma (MCL), demonstrated a significant benefit in progression-free survival (PFS) as well as improved tolerability for B-R compared with CHOP-R. Here we present an analysis of the impact of response quality on outcome. Methods: 514 patients (pts) with indolent or MCL were randomized to receive B-R or CHOP-R for a maximum of 6 cycles. Results: The overall response rate in the 514 pts (261 B-R; 253 CHOP-R) was 92.7% and 91.3% in the B-R and CHOP-R arms, respectively (as presented at the last ASCO meeting, J Clin Oncol 30, 2012 (suppl; abstr 3). A complete response (CR) was observed in 39.8% in the B-R arm and in 30% in the CHOP-R arm (p=0.021). The achievement of CR was associated with a significantly prolonged PFS and overall survival (OS) (Table 1). Analysis by treatment arm revealed a trend for superior PFS and a significantly improved OS for patients achieving CR following treatment with B-R. In the CHOP-R arm, patients in CR had a significantly superior PFS compared to those in PR with a trend to superior OS. Regardless of the quality of response, PFS was superior with B-R versus CHOP-R: For patients in CR, the median PFS was not reached with B-R, whereas for CHOP-R it was 53.7 months (p=0.0204). In patients achieving PR, treatment with B-R resulted in a median PFS of 57.2 months, and this was 30.9 months with CHOP-R (p=0.0002). We noted a statistically significant difference in CR rates between male (n=272, median age 63 years) and female (n=242, median age 64 years) patients. The CR rate was 28.6% in male patients and 42.1% in female patients (p=0.0016). Female patients had a longer median PFS (51.4 months) compared to male patients (38.6 months), however, this difference was not statistically significant (p=0.0866). Conclusions: Patients in CR following first-line treatment in our study had a significantly longer PFS and OS compared to those achieving a PR. Therefore, our results strongly suggest an association between quality of response and outcome. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 3090 Introduction: Long term survival among patients (pts) with low grade/indolent Non-Hodgkin lymphoma (iNHL) is increasingly common, and as a consequence, a consideration of potential therapy-related sequelae, such as secondary neoplasia (sNPL), is of particular importance. Bendamustine plus rituximab (B-R) is an effective treatment option with a favorable toxicity profile in pts with iNHL. However, no data have been reported concerning later, therapy-associated complications with B-R. The aim of this study was to determine the incidence of therapy-related myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and solid tumors after B-R, in comparison with other anti-lymphoma chemotherapy regimens, in pts with follicular (FL), other indolent or mantle cell lymphoma (MCL). Patients and methods: Data for this analysis were obtained from 2 randomized studies, including a total of 697 pts: 1) StiL-study NHL-1, comparing B-R (bendamustine 90 mg/m2, d1+2, rituximab 375 mg/m2, d1; q 28 days) with CHOP-R (q 21 days) as first-line therapy in 513 pts (260 B-R, 253 CHOP-R) (median age 64 yrs, range 31–83); 2) StiL-study NHL-2, comparing B-R with F-R (fludarabine 25mg/m2, d1–3, rituximab 375mg/m2, d1; q 28 days) in 184 pts (median age 68 yrs, range 38–87) with relapsed disease (96 B-R, 88 F-R). Patients in this NHL-2 study had received a median of 1 prior therapy (range 1–7). Result: At the time of this analysis (May 2010), the median observation time was 35 months for NHL-1 pts and 33 months for NHL-2 pts. Most pts in both studies received 6 cycles of therapy. In the NHL-1 study, 16 pts (6.2%) developed sNPL after B-R as first-line treatment, compared with 19 (7.5%) after CHOP-R. Most (87.5%) sNPL were solid tumours: 4 gastrointestinal, 4 urothelium, 2 prostate, 2 squamous epithelium, 1 bronchial, and 1 adrenal after B-R; 6 gastrointestinal, 5 prostate, 3 bronchial, 2 breast, 1 melanoma, 1 urothelium, and 1 endocrinal pancreas after CHOP-R. The rate of secondary hematological NPL did not differ between arms; 1 MDS and 1 T-cell-lymphoma after B-R, 1 AML and 1 Hodgkin lymphoma after CHOP-R. The median time from initiation of study therapy to diagnosis of sNPL was 18.5 months for B-R, and 14 months for CHOP-R. 5 pts in the B-R group, and 2 in the CHOP-R group received additional chemotherapy after completing study therapy, and before diagnosis of sNPL. In the NHL-2 study, 6 pts (6.3%) developed sNPL after B-R as relapse therapy, compared with 9 (10.3%) after F-R (p=0.42). Of these, 3 pts in the B-R group, and 2 pts in the F-R group developed a secondary hematological NPL (2 MDS, 1 Hodgkin lymphoma after B-R; 2 AML/MDS after F-R). Solid tumors were observed in 3 pts following B-R (2 urothelium, 1 squamous epithelium), and in 8 pts following F-R (3 squamous epithelium, 2 bronchial, 1 gastrointestinal, 1 urothelium, 1 anal). The median time from initiation of study therapy to diagnosis of sNPL was 33 months for the B-R group and 24.5 months for the F-R group. Conclusion: This ongoing evaluation shows comparable rates of secondary MDS/AML and other sNPL between B-R and CHOP-R or F-R. This observation, combined with data from other studies showing improved efficacy with B-R compared with CHOP-R or F-R, confirm the value of B-R as a treatment option in patients with follicular, indolent or MCL. Longer follow-up of the patient cohorts reported here will provide important additional information on the rate of sNPL with B-R compared with other anti-lymphoma regimens. Disclosures: No relevant conflicts of interest to declare.