Bendamustine has been shown to produce a clinically meaningful response in patients with indolent B-cell non-Hodgkin's lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen.

Promising results were observed in two Phase II studies evaluating the combination of bendamustine plus rituximab (B-R) in patients with relapsed/refractory follicular (FL), other indolent or mantle cell lymphomas (MCL).^1,2 As fludarabine plus rituximab (F-R) is an established treatment option in this setting, a multicentre, randomised Phase III study was designed to compare the efficacy and safety of B-R versus F-R for patients with FL, indolent or mantle cell lymphomas (MCL).³

The study found that progression free survival was significantly prolonged with B-R compared with F-R (30 versus 11 months, p<0.0001).

The overall response rate (83.5 vs 52.5%, p< 0.0001) and CR rate (38.5 vs 16.2%; p=0.0004) were also significantly higher with B-R than with F-R. Overall survival did not differ significantly between arms, with 42 and 46 deaths documented in the B-R and F-R arms, respectively.

Long term survival among patients 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 favourable toxicity profile in patients with iNHL. However, no data have been reported concerning later, therapy-associated complications with B-R.

Data was presetned at ASH 2010 on the incidence of therapy-related myelodysplastic syndromes (MDS), acute myeloid leukaemia (AML) and solid tumours after B-R versus other anti-lymphoma chemotherapy regimens, in patients with FL, other indolent or MCL.⁴ Comparable rates of secondary MDS/AML and other sNPL between B-R and CHOP-R or F-R were reported.

The investigators concluded that these results, which provide important additional information on the rate of sNPL with B-R compared with other anti-lymphoma regimens, confirm the value of B-R as a treatment option in patients with follicular, indolent or MCL.

BEAM (Carmustine, etoposide, cytarabine, and melphalan) regimen is the most used conditioning regimen before autologous stem cell transplant (ASCT) in lymphoma patients. However, patients receiving BEAM show a significant number of side effects, and relapse rate after transplant is still a matter of concern. Therefore, new regimens with a higher efficacy and a better toxicity profile in comparison to BEAM are needed.

A Phase I-II study to evaluate the safety and the efficacy of increasing doses of bendamustine for the conditioning regimen to ASCT for resistant/relapsed lymphoma patients was presented at ASH 2010.⁵ The new conditioning regimen consisted of increasing doses of bendamustine coupled with fixed doses of etoposide (200mg/m2/day on days -5 to -2), cytarabine (400mg/m2 on days -5 to - 2) and melphalan (140 mg/m2 on day -1) (BeEAM regimen). Three cohorts of 3 patients each were treated starting with bendamustine 160 mg/m2/daily given on days -7 and -6. The dose of bendamustine was then escalated according to the Fibonacci's increment rule until the onset of severe adverse events and/or the attainment of the expected maximum tolerated dose, but not higher than 200 mg/m2.

Patients were carefully monitored for adverse events. The administration of bendamustine was safe in all the 3 cohorts of patients and a dose of bendamustine 200 mg/m2 was considered appropriate for the Phase II study. This new BeEAM regimen was found to be safe and seemed to have a high efficacy in heavily pretreated lymphoma patients. Basing on this experience, future studies incorporating bendamustine in conditioning regimens pre-ASCT in lymphoma patients using Bendamustine 200 mg/m2/day over 2 days are planned.

References

1. Rummel et al JCO 2005

2. Robinson et al JCO 2008

3. MJ Rummel, U Kaiser, C Balser et al Bendamustine Plus Rituximab Versus Fludarabine Plus Rituximab In Patients with Relapsed Follicular, Indolent and Mantle Cell Lymphomas – Final Results of the Randomized Phase III Study NHL 2-2003 on Behalf of the StiL (Study Group Indolent Lymphomas, Germany) Abstract 856 presented at 52nd ASH, Orlando, FL, December 4-7, 2010

4. MJ Rummel, A Tenzer, N Niederle et al No Elevated Rates of Treatment-Related Myelodysplastic Syndromes and Second Solid Tumors Following Therapy with Bendamustine Compared with Other Anti-Lymphoma Regimes for Low-Grade Non-Hodgkin's Lymphoma Abstract 3090 presented at 52nd ASH, Orlando, FL, December 4-7, 2010

5. G Visani, L Malerba, PM Stefani et al A Novel High Dose Chemotherapy Strategy with Bendamustine In Adjunct to Etoposide, Cytarabine and Melphalan (BeEAM) Followed by Autologous Stem Cell Rescue Is Safe and Highly Effective for the Treatment of Resistant/Relapsed Lymphoma Patients: a Phase I-II Study on 44 Patients Abstract 31 presented at 52nd ASH, Orlando, FL, December 4-7, 2010