PF301 REDUCED‐INTENSITY IMMUNOCHEMOTHERAPY WITHOUT VINCRISTINE IN ELDERLY PATIENTS OLDER THAN 80 YEARS OLD WITH DIFFUSE LARGE B‐CELL LYMPHOMA: A MULTICENTRE, OPEN‐LABEL, SINGLE‐ARM, PHASE II TRIAL

Background: In patients with diffuse large B‐cell lymphoma (DLBCL) older than 80 years, treatment intensities must be lowered due to risks of comorbidities and organ dysfunction, and treatment outcomes are worse compared to that in younger patients. Such elderly patients are often excluded from clinical trials, and optimal treatments and dosages are not established. Aims: We examined the efficacy and safety of 6 cycles of reduced‐dose immunochemotherapy in which vincristine was omitted to avoid peripheral neuropathy that reduces the quality of life of DLBCL patients older than 80 years. Methods: We did a prospective, multicenter, single arm, phase 2 study of DLBCL patients aged over 80 years. The main inclusion criteria are as follows. (1) clinical stage I bulky to IV; (2) no prior therapy for lymphoma except pre‐treatment with prednisolone; (3) Performance Status (PS) (ECOG) 0–2; (4) adequate organ functions. Patients received 6 cycles of R‐mini CHP therapy, in which R‐mini CHOP was modified as cyclophosphamide was escalated to 500 mg/m 2 instead of vincristine omission (375 mg/m 2 /day rituximab, 25 mg/m 2 /day doxorubicin, 500 mg/m 2 /day cyclophosphamide, 40 mg/m 2 /day prednisolone). Primary endpoint was the 2‐year PFS rate. Secondary endpoints were the 2‐year OS, the response rate (CRR and ORR) and adverse events (AEs). Survival results were analyzed on an ITT basis. This study was registered with UMIN‐CTR [ www.umin.ac.jp/ctr/ ], identification number UMIN000011234. Results: Forty‐four patients were enrolled between May 2013 and October 2016 from 13 centres of the National Hospital Organization (NHO) in Japan, and 43 patients (16 males, 27 females) were included in the ITT analysis. The median age was 84 years (range 80–92). Twenty‐five patients (58%) had stage III/IV. LDH level was elevated in 27 patients (63%). Thirty‐four patients (79.0%) had ECOG PS scores ≥1: 13 (30%) of score 0, 21 of (49%) of score 1, and 9 of (21%) of score 2. Eight (19%), 12 (28%), and 19 (44%) and 4 patients (9%) had low, low/intermediate, high/intermediate, and high risk according to IPI risk stratification, respectively. Among 43 patients, 35 (81%) completed 6 cycles. The reasons of discontinuation were 2 PDs, 3 AEs, 2 withdrawals of consent, and 1 sudden death. The dose intensity of all patients was maintained at 100% for both doxorubicin and cyclophosphamide throughout the cycles. Twenty‐two (63%) of 35 patients who completed 6 cycles received at least one injection of G‐CSF. The ORR and CRR were 95.3% and 84%, respectively. At the cut‐off date (October 2018), the median follow‐up time was 29 months. The 2‐year PFS and OS were 64.0% [95% CI: 50.3–74.8%] and 71.1% [95% CI: 57.7–81.0%], respectively. Among 37 cases of AEs of any grade reported throughout the treatment period, 19 were Grade 3 or higher. Hematologic toxicity was the most common AE but was generally mild. Grade 3/4 neutropenia was observed in one patient besides febrile neutropenia (FN) and no cases of grade 3–4 thrombocytopenia were reported. Among 227 treatment cycles, 4 episodes of FN (1.8%) were noted in 3 patients. One died during the treatment due to sudden death. Additionally, 4 grade 3 infections, 2 grade 3 thromboembolic events, and 2 grade 3 hyperglycaemias were observed. Peripheral neuropathy was not observed in all patients. Fifteen patients (35%) died during follow‐up periods due to lymphoma (n = 12) and other causes (n = 3). Summary/Conclusion: Vincristine‐omitted R‐mini CHP is a promising chemotherapy regimen that is not associated with peripheral neuropathy, and has a good efficacy and safety in DLBCL patients older than 80 years old.