Are Patient or Disease Characteristics Associated with Complete Response or Progression During Bendamustine-Rituximab Treatment in Previously Treated Patients with Non-Hodgkin's Lymphoma?.
Authors: Mwamburi Mkaya , Ranganathan Gayatri , Mayo Debra , Tremmel Lothar , Zaks Tal Z. , Rummel Mathias J. 
Published: October 2019

Abstract
Abstract 5002

Background
Bendamustine (Treanda®) plus rituximab (Rituximab® and MabThera®) combination (BR) is highly effective in previously treated patients with non-Hodgkin's lymphoma (NHL). Previous studies that individually evaluated the impact of BR used relatively small sample sizes (Rummel et al, Robinson et al) without characterizing factors that influence outcomes. The aim of this study was to re-evaluate the response rates and progression-free survival (PFS) and to explore the predictors associated with overall response rate (ORR) i.e. partial response (PR) or better, complete response (CR) and PFS during BR using pooled data from Rummel et al and Robinson et al. Understanding the predictors of response and progression to treatment may help clinicians optimize the impact of treatment.

Patients and Methods
A total of 129 patients, who had a median age of 62 years (range 40–84) and were 61% male, were included in the combined analysis. A larger proportion of patients in the Rummel study had bone marrow and spleen involvement. Other characteristics were similar, and patients in both studies were given similar regimens. The treatment doses were 90 mg/m2 of bendamustine as a 30-minute infusion on days 1 and 2 combined with 375 mg/m2 rituximab on day 1 for 4 to 6 cycles. Patients from both studies also received a single dose of rituximab 1 week before the first cycle and 4 weeks after the last cycle. Response and progression were based on International Working Group Response Criteria for NHL in both the Robinson study and the Rummel study. Histological types were 28 (22%) mantle cell, 64 (49%) follicular, 10 (8%) small lymphocytic, 19 (15%) lymphoplasmacytoid, and 8 (6%) marginal zone lymphoma. We explored factors associated with a) ORR and CR following BR treatment using logistic regression modeling and b) PFS following BR treatment using Cox proportional hazard modeling. Age, gender, histological type, bone marrow involvement, spleen involvement, number of prior treatment regimens and hematologic toxicities were reported in a similar format across both studies.

Results
The ORR for BR was 91% (118/129), corresponding to CR and PR rates of 57% (74/129) and 34% (44/129), respectively. The median time of PFS was 24 months for the Rummel study and 23 months for the Robinson study. The median PFS for the combined data is being analyzed. Baseline factors explored as potential predictors of ORR, CR and PFS were age, gender, histological type, bone marrow involvement, spleen involvement, number of prior treatment regimens. In the logistic regression analysis, no factors were associated with ORR. Gender (men vs. women), odds ratio (OR) = 0.27 (95% confidence interval (CI): 0.12, 0.62, p=0.002), and Stage IV (vs. stage I-III), OR= 0.3 (95%CI: 0.12, 0.75, p=0.01), were significantly associated with an inferior CR. Bone marrow involvement and spleen involvement were not significantly associated with CR. None of the factors were significantly associated with PFS.

Conclusion
Pooling the data from 2 studies facilitated the evaluation of predictors of progression in this setting. BR treatment is a highly active regimen in the treatment of NHL in previously treated populations with an ORR greater than 90%. However, men and patients in Stage IV were less likely to achieve CR. The lack of association between patient and disease characteristics and PFS during BR treatment suggests that BR is effective in slowing progression regardless of age, gender, number of prior treatment regimens, bone marrow involvement, and spleen involvement at the start of treatment.

Disclosures
No relevant conflicts of interest to declare.