Update Shows Frontline Bendamustine/Rituximab Improves TTNT in NHL

Mathias J. Rummel, MD, PhD

Ten-year follow-up results from the StiL NHL1 study showed that frontline bendamustine (Treanda) plus rituximab (Rituxan) improved time-to-next-treatment (TTNT) compared with CHOP-R in patients with indolent lymphomas.

The median TTNT was not yet reached with bendamustine plus rituximab (BR) versus 56.0 months with CHOP-R (hazard ratio [HR], 0.55; 95% CI, 0.41-0.73; P <.0001). Rummel said TTNT corresponded closely with progression-free survival (PFS). As shown in previously published results, PFS was 69.5 months for BR compared with 31.2 months for CHOP-R (HR, 0.58; 95% CI, 0.44-0.74; P = .0000148).

Longer TTNT translates into less secondary treatment, Mathias J. Rummel, MD, PhD, professor of medicine at the University Hospital Giessen in Germany, said during his presentation at the 2017 ASCO Annual Meeting. At 117 months’ follow-up, 77 patients assigned to BR required secondary treatment compared with 109 patients assigned to CHOP-R. Fifty-two patients assigned to CHOP-R were treated with the BR combination as secondary treatment. Twenty-seven patients assigned to BR had CHOP-R as secondary treatment.

“Very clearly, patients with initial treatment of bendamustine and rituximab needed less secondary treatment,” said Rummel.

In the multicenter, randomized phase III StiL NHL1 trial, patients with indolent lymphomas were randomly assigned to 6 cycles of BR (n = 215) or CHOP-R (n = 205). Most patients in the study were diagnosed with follicular lymphoma (66%).

The main endpoints for this follow-up analysis were overall survival (OS), TTNT, and secondary malignancies.

“Why did we not ask for progression-free survival?” Rummel said. “If a patient is in ongoing remission for 5, 7, or even 10 years, he will not go to CT scans or even to sonography. Also, according our results, the time-to-next-treatment can be used as a surrogate for disease control.”

Investigators did not find any difference in secondary malignancies between the 2 groups. Thirty-seven patients in the BR group reported 39 secondary malignancies compared with 47 secondary malignancies among 40 patients in the CHOP-R group.

Unlike PFS, the combination did not significantly improve OS. OS was 70.3% for patients assigned to BR compared with 66.3% in the CHOP-R group (HR, 0.82; 95% CI, 0.59-1.16; P = .2665). Investigators observed 62 deaths in the BR arm versus 71 in the CHOP-R arm. For responding patients, 10-year OS was 73.9% with 51 deaths in the BR group compared with 70.0% with 58 deaths in the CHOP-R group (HR, 0.81; 95% CI, 0.55-1.17; P = .2630).

“We are very happy to see a long-term follow-up. We always focus on PFS when we report study results for indolent lymphomas. We always say, ‘We want to see the overall survival.’ Therefore, I think this is very important data,” Rummel said. “What is the long-term overall survival? What we see here is, despite patients with BR having less second-line treatment—or maybe because&mdash;they have more or less the same overall survival.”

However, there was a clear OS benefit for patients who had complete response compared with those who had partial response (80.8% vs 66.5%; HR, 0.50; 95% CI, 0.36-0.77; P = .0011). There were 30 deaths among complete responders and 79 among partial responders. Similarly, patients with normal LDH had superior OS compared with patients with elevated LDH levels (HR, 0.45; 95% CI, 0.29-0.61; P <.0001).

There were 133 deaths in the study (31.7%). Eighty-six patients (65%) died of relapsed lymphoma. Forty-seven (35%) died in first remission, 40% of whom experienced secondary malignancies. Rummel said it was not clear whether those patients died of their secondary malignancies, but that would explain the deaths that occurred in first remission without relapse.

Rummel MJ, Maschmeyer G, Ganser A, et al. Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: Nine-year updated results from the StiL NHL1 study. J Clin Oncol 35, 2017 (suppl; abstr 7501).