Dear Editor,
Bendamustine- rituximab (BR) is now considered as a standard regimen for advanced and symptomatic follicular lymphoma (FL), after the results of two landmark phase III trial [1, 2]. There is the paucity of data regarding the safety and efficacy of BR in treatment naïve FL patients from the Indian subcontinent. This study aimed to evaluate response rate, progression-free survival (PFS), and safety of BR in treatment naïve patients of FL at our center. It is a retrospective study performed at the Department of Medical Oncology, All India Institute of Medical Sciences (AIIMS), New Delhi, between the period of May 2013 and June 2017.
Fifty-one patients of FL were included for analysis. The median age of our study population was 53 years (33–72) with equal sex distribution. The stage distribution was: stage II—9%, stage II—11%, stage III -22% and stage IV—58%. Extranodal involvement and bulky disease were present in 29.4% and 23.5% patients respectively. The most common sites of extra-nodal involvement were gastrointestinal in six patients followed by bone in four, head/neck region in three and combination in two cases. Follicular Lymphoma International Prognostic Index (FLIPI) 1 score: good − 7.8%, intermediate—23.5% and high risk in 62.6% of cases. The disease characteristics are given in Table 1.
Table 1.
Baseline characteristics of follicular lymphoma patients
| Characteristics | Study population, n = 51 (%) |
|---|---|
| Age, median, range | 53 years (33–72 years) |
| Stage | |
| II | 5 (9.8%) |
| III | 5 (21.56%) |
| IV | 35 (68.63%) |
| ECOG PS | |
| 0, 1 | 32 (62.7%) |
| 2 | 14 (27.4%) |
| 3 | 4 (7.8%) |
| 4 | 1 (1.9%) |
| LDH | |
| Normal | 34 (66.7%) |
| Abnormal | 14 (27.4%) |
| Not available | 3 (5.9%) |
| Grade | |
| 1 | 30 (58.8%) |
| 2 | 12 (23.5%) |
| 3a | 4 (7.8%) |
| Not available | 5 (9.8%) |
| FLIPI | |
| Good | 4 (7.8%) |
| Intermediate | 12(23.5%) |
| High | 32 (62.7%) |
| Not available | 3 (5.9%) |
| B symptom present | 20 (39.2%) |
| Bulky disease | 12 (23.5%) |
| Extra nodal involvement | 15 (29.4%) |
Forty-five patients (88%) received 6 cycles BR and 15 patients (29.4%) received rituximab maintenance. The complete response (CR) rate was 64.7% and an overall response rate (ORR) was 88.23% in this study. With a median follow up of 36 months, the median PFS was not reached and 5 years PFS was 55%. A total of 14 events were recorded (10 relapses, 3 progressions and one induction death). A total of 9 deaths were recorded (one due to chemotoxicity, 6 due to disease and 2 due to other causes). The most common hematological toxicities (grade 3–4) were neutropenia 15.7% (n = 8), thrombocytopenia 3.9% (n = 2) and anemia 3.9% (n = 2). The most common non-hematological all grade toxicities of BR were skin rash (33.7%), infections (15.7%) and diarrhea (5.8%). Two patients had discontinued the treatment after 2 cycles because of severe skin toxicity and in 3 patients dose modification was required.
The median age of this study was 53 years which was similar to the previous study of FL [3]. In this retrospective study, the CR rate was 64.7% in the total study population. The CR rate was higher than the prospective phase III randomized trials [1, 2, 6]. The difference could be due to different study design and study population. In a retrospective analysis by Rummel et al., the CR rate of BR in low-grade NHL and MCL was 63%, but they used 4 cycles of BR [4]. The OR rate of BR in this study was 94% which was similar to randomized and retrospective studies [4–6].
In this study, we found G3-4 neutropenia including febrile neutropenia [6 (11.8%)] was 15.7% of patients, which was similar to a retrospective study. Grade 3–4 thrombocytopenia was 3.9% and anemia was 3.9% in this study which was higher compared to previous western retrospective study but less compared to randomized trials [1, 2, 6]. These differences could be due to different study disease populations, as these study included various low-grade lymphoma and MCL patients. The most common non-hematological toxicities of BR were skin rash (33.7%), infections (15.7%) and diarrhea (5.8%) in these studies. This was more compared to previous retrospective studies and randomized trials [1–6]. The major concern with BR is cutaneous toxicity in our population. The reason for a skin rash was the drug (bendamustine), as the rashes subsided after completion of chemotherapy and there was no association with concomitant medicines used. The reason for this cutaneous toxicity is unclear but the postulated hypothesis is, either inflammatory response due to the bendamustine or acute interface dermatitis [7]. The BR regimen showed good CR rate, ORR with acceptable toxicity in the treatment of naive FL patients.
Funding
No funding received for the study.
Compliance with Ethical Standards
Conflict of Interest
There is no conflict of interests for all 5 authors.
Ethical Approval
The study is in compliance with ethical standards. Institute ethical clearance was obtained for the retrospective study.
Footnotes
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Contributor Information
Ajay Gogia, Email: ajaygogia@gmail.ccm.
Sudhir Kumar, Email: sudhirkirar@gmail.com.
Lalit Kumar, Email: lalitaiims@yahoo.com.
Atul Sharma, Email: atul1@hotmail.com.
Soumya Mallick, Email: drsmallick.aiims@gmail.com.
References
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