Bendamustine Plus Rituximab (B-R) Versus CHOP Plus Rituximab (CHOP-R) As First-Line Treatment in Patients with Indolent and Mantle Cell Lymphomas (MCL) – 7 Year Updated Results from the StiL NHL1 Study

Background: This multicenter, randomized, phase III study compared B-R and CHOP-R as first-line treatment in patients (pts) with indolent lymphomas or MCL and was presented at ASH 2009, ASCO 2012, and published in The Lancet in 2013. The final published analysis at a median follow-up of 45 months demonstrated a significantly prolonged progression-free survival (PFS) in the B-R group, compared to the CHOP-R group (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.44–0.74; p<0.001). Median PFS was 69.5 vs. 31.2 months, respectively. In the current analysis, we present updated results for overall survival (OS), time-to-next-treatment (TTNT), and secondary malignancies (sNPL) with a median follow-up of 87 months.

Methods: 549 pts with indolent lymphomas or MCL were randomized to receive B-R or CHOP-R for a maximum of 6 cycles. The primary endpoint was PFS; secondary endpoints included OS, TTNT, and sNPL.

Results: 514 randomized pts were evaluable (261 B-R; 253 CHOP-R). Patient characteristics were well balanced between arms; median age was 64 years.

Fewer pts treated initially with B-R needed second-line treatments due to disease progression compared to CHOP-R treated pts: 93 pts (36%) in the B-R group received salvage treatment compared with 140 pts (55%) in the CHOP-R group. Of those in the CHOP-R group, 69 pts (49%) received B-R as salvage. TTNT was significantly prolonged with B-R compared with CHOP-R (HR 0.53, 95% CI 0.40-0.68; p<0.001). Median TTNT was not yet reached in the B-R group vs. 42.3 months in the CHOP-R group.

The difference in complete response (CR) rates (independent of treatment arms) between male (n=272, median age 63 years) and female (n=242, median age 64 years) pts was statistically significant: 28.6% for male pts versus 42.1% for female pts (p=0.0016). Female pts had a longer median TTNT compared to male pts (not yet reached vs. 52.2 months, respectively; HR 0.70, 95% CI 0.54-0.90; p=0.006). The achievement of a CR was associated with significantly prolonged OS, with an estimated 10-year survival rate of 72.6% for pts with a CR and 63.6% for pts with a partial response (p=0.006).

The difference in OS between the treatment arms was not statistically significant, with 65 and 76 deaths in the B-R and CHOP-R arms, respectively. The estimated 10-year survival rates were 67.4% for B-R and 60.1% for CHOP-R (p=0.262). In pts with indolent lymphomas (total group without MCL), there was a trend toward longer survival for the B-R group compared with the CHOP-R group, with 43 deaths out of 215 pts (20.0%) in B-R and 58 deaths out of 205 pts (28.3%) in CHOP-R. The estimated 10-year survival rates for pts with indolent lymphomas were 71.9% for B-R and 61.5% for CHOP-R (HR 0.70, 95% CI 0.48-1.04; p=0.076). No difference in OS was found in the subgroup of pts with MCL (n=95) (HR 1.28, 95% CI 0.69-2.39; p=0.429).

Twenty sNPL were observed in the B-R group compared with 23 in the CHOP-R group, with 1 hematological malignancy in each group (1 MDS in B-R, 1 AML in CHOP-R) to date. Updated sNPL results will be presented at the ASH meeting.

Conclusions: In pts with previously untreated indolent lymphomas, and in elderly pts with MCL, B-R demonstrates a PFS and TTNT benefit over CHOP-R. OS for the entire group of patients was not significantly different while treatment with B-R resulted in a trend toward survival benefit in the group of pts with indolent lymphomas.