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.

Abstract

7501 Background: This multicenter, randomized, phase III study compared B-R and CHOP-R as first-line treatment in patients (pts) with indolent lymphomas or mantle cell lymphoma and was first published in The Lancet in 2013. The final analysis demonstrated a significantly prolonged progression-free survival (PFS) in the B-R group compared to the CHOP-R group, with a median PFS of 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 113 months for patients with indolent lymphomas (excluding MCL). Methods: 447 pts with indolent lymphomas 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: Patient characteristics were well balanced between arms; median age was 64 years. The difference in OS between the two treatment arms was not statistically significant, with 60 deaths in the B-R group vs 68 deaths with CHOP-R (HR 0.82, 95% CI 0.58 – 1.15, p = 0.249). The estimated 10-year survival rates were 71% for B-R and 66% for CHOP-R. TTNT was significantly prolonged with B-R compared with CHOP-R (HR 0.52, 95% CI 0.38 – 0.69, p < 0.001). Median TTNT was not yet reached in the B-R group (95% CI 124.9 – n.y.r) vs. 56 months in the CHOP-R group (95% CI 39.1 – 82.0). Patients treated initially with B-R needed fewer second-line treatments due to disease progression compared to CHOP-R treated pts: 73 pts (34%) in the B-R group received salvage treatment compared with 106 pts (52%) in the CHOP-R group. For B-R pts, CHOP-R was used as second-line therapy 26 times (36%), whereas B-R was used for pts initially treated with CHOP-R 49 times (46%). 36 pts with sNPL were observed in the B-R group compared with 39 in the CHOP-R group, with 7 hematological malignancies in both groups to date. Conclusions: In pts with previously untreated indolent lymphomas, B-R demonstrates a PFS and TTNT benefit over CHOP-R. Clinical trial information: NCT00991211.

Long‐term overall‐ and progression‐free survival after pentostatin, cyclophosphamide and rituximab therapy for indolent non‐Hodgkin lymphoma

“…The latter study-a phase III randomized clinical trial that included 46 MZL patients who were treated with either BR versus R-CHOP or R-CVP-revealed CR rates of 20% and 24% and combined (CR + PR) rates of 92% and 72% for the two treatments, respectively. Updated results from both studies do not differentiate PFS by histological subtype (Flinn et al, 2017;Rummel et al, 2017), however we eagerly await those complete findings. The low number of patients with MZL and lack of reports with 10-year follow-up underscore the uniqueness of our data, which show 10-year PFS of 67% after PCR treatment.…”

“…The 5‐year OS rate of 87% in our study was similar to those of the BRIGHT study: 82% and 85% in the BR and R‐CHOP arms, respectively. The StiL patients received 6 cycles, and their team reported 10‐year rates (Rummel et al , ). Our patient group had a 10‐year OS rate of 64%, comparable with the estimated OS rates reported by the StiL study: 71% and 66% in their BR and R‐CHOP arms, respectively (Rummel et al , ).…”

“…The StiL patients received 6 cycles, and their team reported 10‐year rates (Rummel et al , ). Our patient group had a 10‐year OS rate of 64%, comparable with the estimated OS rates reported by the StiL study: 71% and 66% in their BR and R‐CHOP arms, respectively (Rummel et al , ). However, only a properly powered and randomized trial can provide clinically meaningful efficacy or safety information about these different regimens.…”

The potential for chemotherapy-free strategies in mantle cell lymphoma

“…6 Less-intensive regimens have also been reported to produce durable remissions, with emerging evidence that patient-related factors and disease biology trump choice of therapy in impacting outcomes. 1,7,8 Moreover, chemotherapy may have some desirable effects beyond simple cytotoxicity: cyclophosphamide may inhibit regulatory T cells (Tregs), 9 doxorubicin may impair myeloidderived suppressor cells, 10 and low-dose metronomic therapy may impact tumor angiogenesis. 11 Nonetheless, the most effective immunochemotherapy regimens are restricted to young, healthy patients who account for ,25% of all patients.…”

Author reply

“…Although we acknowledge that FL is incurable, the prolonged remissions seen following effective first line therapy likely provides a ‘functional cure’ for many patients (who have a median age at presentation of 60). For younger patients, with an anticipated median PFS beyond 15 years after anti‐CD20 antibody‐bendamustine chemotherapy, we can anticipate for most patients any CD4 lymphopenia will have resolved at the time of any relapse . Martinez‐Calle reported a median time to lymphocyte count recovery (≥1 × 10 9 /L) following bendamustine of 26 months with rituximab maintenance associated with further delays in recovery .…”