The addition of carfilzomib to rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) is well-tolerated. The therapeutic cocktail leads to a high response rate, especially in patients with nongerminal center B-cell-like (nonGCB) diffuse large B-cell lymphoma (DLBCL), according to a new study published in the journal Blood Advances

Patients with refractory DLBCL or those whose disease relapsed within 12 months of frontline therapy have significantly lower response rates to subsequent chemoimmunotherapy, Pallawi Torka, of the Roswell Park Comprehensive Cancer Center in Buffalo, New York, and colleagues, noted. Such patients “should be considered for alternate therapies such as anti-CD19 CAR-T cell therapy,” the study authors noted.

The investigators conducted a single-center, open-label, prospective phase 1 study to evaluate the safety and efficacy of carfilzomib together with R-ICE in eligible patients with relapsed/refractory DLBCL. They called this treatment regimen C-R-ICE. They enrolled 18 patients at 6 dose levels of carfilzomib.

They noted no dose-limiting toxicities and selected a dose of carfilzomib of 45 mg/m2 for further testing. They then enrolled 11 more patients to be treated as part of the dose expansion phase of the study.

Read more about the treatment of DLBCL

The overall response rate of the participants was 66%. More than half of the patients (52%) underwent high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT). 

Patients with nonGCB DLBCL had an overall survival rate of 85%, while the overall survival rate of those with GCB DLBCL was only 13%. 

The median progression-free survival was 15.2 months, and the median overall survival was 22.6 months. The progression-free and overall survival of patients with nonGCB DLBCL were significantly longer than those with GCB DLBCL. 

The researchers concluded that C-R-ICE was well-tolerated in patients with relapsed/refractory DLBCL and that toxicities were comparable to R-ICE therapy. 

“Our data show that [patients] with nonGCB DLBCL benefit significantly from incorporating [carfilzomib] into second-line therapy and HDC-ASCT,” they said. 

References

Torka P, Groman A, Wong J, et al. Carfilzomib combined with rituximab, ifosfamide, carboplatin, and etoposide for relapsed or refractory DLBCL. Blood Adv. Published online November 14, 2022. doi:10.1182/bloodadvances.2022008543

Carfilzomib, rituximab, ifosfamide, carboplatin, and etoposide in treating patients with relapsed or refractory stage I-IV diffuse large B-cell lymphoma. US National Library of Medicine. Updated July 21, 2022. Accessed November 21, 2022.