Peripheral Blood Stem Cell Mobilization After Bendamustine Containing Chemotherapy in Indolent Lymphomas Is Possible. Results From the Phase III Study of B-R Vs. CHOP-R (NHL 1-2003 trial) of the StiL (Study group indolent Lymphomas, Germany).

Bendamustine, a hybrid alkylating agent, shows a unique mechanism of action with a good toxicity profile in various hematological malignancies, particularly in non-Hodgkin's lymphoma. Bendamustine (B) in combination with Rituximab (R) was demonstrated to be an effective regimen in first- or second-line treatment of patients (pts) with indolent lymphomas. So far, however, no data about the capacity of peripheral blood stem cell (PBSC) mobilization or a possible stem cell toxicity of B has been studied. It is still an open and clinically relevant question, if pts treated with B are able to mobilize enough stem cells for subsequent high dose therapy with autologous stem cell support.

We performed a prospective randomized multicenter phase-III trial to compare the efficacy and safety of the combination of Bendamustine plus Rituximab (B-R) versus CHOP plus Rituximab (CHOP-R) as first-line therapy for follicular, indolent and mantle cell lymphomas. Chemotherapy was given in 6 cycles each (B: 90 mg/m² d1+2). One of the secondary objectives (not mandatory) of this study was to evaluate the possibility to mobilize a sufficient number (at least 2.0 × 10E6 CD 34+ cells/kg) of PBSC and progenitor cells in younger pts after completing either B-R or CHOP-R and to compare both stem cells yields.

549 pts have been randomized, 513 pts (B-R = 260, CHOP-R = 253) are evaluable. In each arm, 23 PBSC mobilizations have been performed. In the B-R as well as in the CHOP-R arm each 18 mobilizations were performed directly after completion of therapy, and in 5 pts stem cells were collected at the time of first relapse. Patient characteristics: initial bone marrow involvement was observed in 17 of 23 pts in the B-R arm and 14 of 23 pts in the CHOP-R arm, respectively. Median patient age was 51 years (B-R) and 53 years (CHOP-R). The mobilization regimen was either high dose cyclophosphamide + G-CSF (9 pts in each arm) or G-CSF alone in 7 pts after B-R and in 2 pts after CHOP-R, respectively. Alternative regimens such as Dexa-BEAM, DHAP, ICE and others were also used in the remaining patients. The median CD34+ cell-count/kg was not significantly different in the two arms with 4.55 × 10E6 CD34+ cells/kg (range 1.68 – 12.35) in the B-R group and 6.17 × 10E6 CD 34+ cells/kg (range 1.68 – 20.39) in the CHOP-R group, respectively. In both arms the medium number of apheresis to achieve these yields was not different (B-R: 1.85 vs. CHOP-R: 1.66). Only 3 pts were not able to mobilize at least 2.0 × 10E6 CD 34+ cells/kg: 1 patient after B-R (1.68 × 10E6 CD 34+ cells/kg), and 2 pts after CHOP-R (1.68 × 10E6 CD 34+ cells/kg, and in 1 patient no mobilization was possible). In patients who were mobilized directly after completion of first-line chemotherapy (18 pts in each arm), again, no differences (B-R: median 5.52 × 10E6 CD 34+ cells/kg vs. CHOP-R: median 7.35 × 10E6 CD 34+ cells/kg) were observed. The yield of stem cells in each 5 pts of both arms who were mobilized at the time of first relapse was also nearly the same (B-R: median 8.79 × 10E6 CD 34+ cells/kg vs. CHOP-R: median 7.3 × 10E6 CD 34+ cells/kg).

Our results demonstrate that the collection of sufficient numbers of PBSC after B-R treatment is possible and appears to be comparable to the PBSC yield after prior treatment with CHOP-R.

Rummel:Roche Pharma AG: Honoraria, Research Funding; Mundipharma: Honoraria, Research Funding.