Page 112 - Haematologica August 2018

S. Storti et al.
a CGA. With the observed 53% CR rate, and with the 15.6% rate of grade 3-4 eeAEs, the study met its primary objectives and shows the promising activity of the com- bination in a difficult-to-treat patient population
Besides the analysis of the main study end points (response rate and safety), we acknowledge that the small sample size of this study does not allow any firm conclu- sions to be drawn on the interpretation of secondary end points, and in particular on PFS and OS data. Moreover, the lack of a centralized histology review and cell of origin analysis does not allow us to present any hypothesis on the differential activity of bendamustine and rituximab combination among DLBCL subtypes.
Since the activity of bendamustine in DLBCL was first documented by Weidmann et al.,15 several phase II and retrospective studies have been published to assess the activity and the safety profile of this combination. In the first prospective studies on relapsed refractory patients, bendamustine was used at higher doses (120 mg/m2/d) and with a shorter interval between cycles.5-7 In these tri- als, the ORR ranged between 46% and 63% (CR 15-37%) and the median PFS between 3.6 and 6.7 months (Table 6). Park et al.8 recently published the results of a small phase II trial of bendamustine at 120 mg/m2 in combination with rituximab in untreated older patients (>65 years) who were poor candidates for R-CHOP. Among the 23 enrolled patients, the median age was 80 years, the ORR and the CRR were 78% and 52%, respectively, but the median PFS and OS were only 5.4 and 10 months, respectively. In our study, in consideration of the patients’ age and frail status, we opted for a regimen with bendamustine at a lower dose of 90 mg/m2 combined with standard ritux- imab doses, and administered every four weeks. Looking at our results, this choice did not seem to significantly reduce treatment activity compared to more intense pub- lished BR regimens. Conversely, the adoption of a less intense BR combination was well tolerated and was a good choice for patients who were prospectively identi-
Table 4. Overall toxicities according to CTCAE v.4.0 categories with grade.
fied as frail. Comparing our data with those from prior phase II reports, it should also be acknowledged that Park et al. did not include stage I disease and had more poor performance status patients, while Weidmann et al. had more early stage patients, and a higher median age (85 years). Our data should also be compared with a previous analysis of 99 elderly frail patients with DLBCL who were analyzed in a prospective observational study.12 The
Figure 1. Estimated progression-free survival (PFS) with 95% confidence inter- val (gray area).
All grades n%n%n%
Grade 3 Grade 4
Anemia
Leucopenia Neutropenia Thrombocytopenia Febrile neutropenia
Infections
Fever
Cardiac disorders
Gastrointestinal disorders
General disorders and administration site conditions* Hepatobiliary disorders Metabolism and nutrition disorders Nervous system disorders
20 44.4 19 42.2 29 64.4 20 44.4 3 6.7
9 20.0 2 4.4 4 8.9 14 31.1
5 11.1 2 4.4 3 6.7 4 8.9 4 8.9 9 20.0 2 4.4
CTCAE: Common Terminology Criteria for Adverse Events; n: number. *Asthenia; laboratory abnormalities; fever. **Other - Grade 1: epistaxis and flu; Grade 2: accidental fall and cough.
1 2.2 3 6.7 8 17.8 4 8.9 0 0.0
2 4.4 0 0.0 1 2.2 0 0.0
1 2.2 0 0.0 1 2.2 0 0.0 1 2.2 0 0.0 0 0.0
0 0.0 2 4.4 9 20.0 0 0.0 1 2.2
0 0 0 0.0 1 2.2 0 0.0
0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0 0 0.0
Renal and urinary disorders
Skin and subcutaneous tissue disorders
Vascular disorders
Other(specify)** 4 8.9 0 0.0
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