Carfilzomib Plus R-ICE Regimen Well-Tolerated Among Patients With Relapsed/Refractory DLBCL

According to findings from a prospective phase 1 study recently published in Blood Advances, the addition of carfilzomib to the rituximab, ifosfamide, carboplatin, and etoposide treatment regimen (R-ICE) was well-tolerated among patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), with toxicities comparable to rituximab, ifosfamide, carboplatin, and etoposide therapy. 

Pallawi Torka, MD, Roswell Park Comprehensive Cancer Center, Buffalo, New York, and coauthors stated, “The outcome of patients with R/R DLBCL is poor, with only 46% eligible for high-dose chemotherapy and autologous stem cell transplant and 12% of ineligible patients achieving long-term event-free survival.”

This study aimed to evaluate the efficacy and safety of carfilzomib combined with R-ICE in high-dose chemotherapy with autologous stem cell transplant eligible patients with R/R DLBCL. The investigators conducted this single-center, open-label, prospective phase 1 study to evaluate the safety and efficacy of carfilzomib in combination with R-ICE in high-dose chemotherapy with autologous stem cell transplant eligible patients with R/R DLBCL. 

In the dose-escalation phase, 18 patients were enrolled at 6 dose levels with no dose-limiting toxicities noted. Carfilzomib 45 mg/m2 was selected as the recommended dose for expansion. 11 additional patients were enrolled in the dose-expansion phase. Overall response rate (ORR) was 66% (48% CR; 17% PR); 52% patients underwent autologous stem cell transplant. 

An ORR of 85% was observed in patients with non-germinal center B-cell-like (non-GCB) DLBCL, compared with only 13% in those with germinal center B-cell-like (GCB) DLBCL. The median progression-free survival (PFS) was found to be 15.2 months (5.1 months to not reached [NR]), and the median overall survival (OS) was 22.6 months (6.8 months to NR). notably, patients with non-GCB subtype had a significantly longer PFS (NR vs 6.6 months; P = .0001) and OS (NR vs 6.6 months; P = .001) than those with the GCB subtype. 

Torka et al concluded, “[Carfilzomib] and R-ICE is well-tolerated in patients with R/R DLBCL with toxicities comparable to rituximab, ifosfamide, carboplatin, and etoposide therapy. Our data show that patients with non-GCB DLBCL benefit significantly from incorporating carfilzomib into second-line therapy and high-dose chemotherapy with autologous stem cell transplant."

Source: 

Torka P, Groman A, Wong J, et al. Carfilzomib combined with rituximab, ifosfamide, carboplatin, and etoposide for relapsed or refractory DLBCL. Blood Adv. March 30, 2023; 7 (7): 1146–1155. doi:10.1182.2022008543