Pixantrone containing R‐CPOP as firstline treatment in elderly DLBCL patients with congestive heart failure or high risk of anthracycline induced cardiotoxicity

Background: R-CHOP remains the standard of care for fit patients with DLBCL up to 80 years. However, anthracyclines as well as liposomal anthracyclines are contraindicated for patients with impaired cardiac function, especially congestive heart failure (CHF). Pixantrone showed reduced cardiotoxicity in vitro compared to standard anthracyclines. Data by Herbrecht et al. (Ann Oncol, 2013, 24:2618) comparing first line R-CHOP with R-CPOP (substituting doxorubicin with pixantrone, 88 mg/m2) in patients with DLBCL resulted in similar PFS with reduced grade 3 CHF rates in R-CPOP patients. Methods: In a prospective, explorative, non-randomized, multicenter phase 2 trial two DLBCL patient cohorts (1. with an age >75, 2. with impaired cardiac function/CHF determined by left ventricular ejection fraction (LVEF) >40% and ≤50%) were recruited. In addition to cohort 2, we conducted a retrospective analysis from patients with even lower LVEF or other strict contraindications to anthracyclines, like prior use, in our center. Patients received up to six cycles of R-CPOP followed by additional 2 cycles of rituximab every 21 days. Results: From 2016 to 2021 we included 51 patients in our analysis (23 and 10 patients in the prospective multicenter trial cohort 1 and 2, respectively; 18 patients in the retrospective analysis). In cohort 1 with a median age of 81.9 years, 2y-PFS and OS of 40% and 47% could be observed. In the combined group of 28 DLBCL patients with an impaired cardiac function the median age was 76 years (range 51–85). 71% had an advanced Ann Arbor stage (III/IV), 71% had an IPI ≥3. The median LVEF was 45% (range 25–63%), 79% patients had a LVEF ≤50%. Median NT-ProBNP was 1814 pg/ml (range: 103–15895). The median number of R-CPOP cycles delivered was 5 (range 1–6). ORR was 82.1%, with 17 patients (60.7%) achieving CR after induction. With a median follow up of 24.7 months, estimated 2y-PFS and OS were 66.5% and 69.2%, respectively. Two patients died during induction (one progression, one by CHF). Concerning serologic parameters for cardiac function, there was no significant change of the median NT-ProBNP from start of induction (654 pg/ml, range 103–1598) to end of treatment (646 pg/ml, range 96–2199) in 15 patients which received at least 4 cycles R-CPOP and achieved a CR. Conclusion: With this trial we could show feasibility and encouraging efficacy of R-CPOP in elderly DLBCL patients with CHF and/or high risk of anthracycline induced cardiotoxicity which invites further trials to establish R-CPOP as standard first line treatment in this patient cohort. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Chemotherapy, Late Effects in Lymphoma Survivors Conflicts of interests pertinent to the abstract. R. Marks Honoraria: Kite/Gilead, Novartis, Abbvie Research funding: CTI, Servier