Carfilzomib combined with rituximab, ifosfamide, carboplatin, and etoposide for relapsed or refractory DLBCL

被引：5

作者：

Torka, Pallawi ^{[1
]}

Groman, Adrienne ^{[2
]}

Wong, Jerry ^{[3
]}

Nichols, Jenna ^{[4
]}

Kader, Angela ^{[4
]}

Mavis, Cory ^{[1
]}

Anampa-Guzman, Andrea ^{[1
]}

Sait, Sheila Jani ^{[5
]}

Block, AnneMarie ^{[5
]}

Przespolewski, Eugene ^{[6
]}

Mohr, Alice ^{[1
]}

Lund, Ian ^{[1
]}

McWhite, Kenneth ^{[1
]}

Kostrewa, Jessica ^{[1
]}

DeMarco, Joseph ^{[1
]}

Johnson, Michael ^{[1
]}

Darrall, Andrea ^{[1
]}

Thomas, Roshneke ^{[1
]}

Sundaram, Suchitra ^{[7
]}

Ghione, Paola ^{[1
]}

Hutson, Alan ^{[2
]}

Hernandez-Ilizaliturri, Francisco J. ^{[1
,8
]}

机构：

[1] Roswell Pk Comprehens Canc Ctr, Dept Med, Buffalo, NY USA

[2] Roswell Pk Comprehens Canc Ctr, Dept Biostat, Buffalo, NY USA

[3] Roswell Pk Comprehens Canc Ctr, Dept Pathol, Buffalo, NY USA

[4] Roswell Pk Comprehens Canc Ctr, Dept Clin Res Serv, Buffalo, NY USA

[5] Roswell Pk Comprehens Canc Ctr, Dept Cytogenet, Buffalo, NY USA

[6] Roswell Pk Comprehens Canc Ctr, Pharm, Buffalo, NY USA

[7] Mt Sinai Icahn Sch Med, Tisch Canc Inst, New York, NY USA

[8] Roswell Pk Comprehens Canc Ctr, Elm & Carlton St, Buffalo, NY 14263 USA

来源：

BLOOD ADVANCES | 2023年 / 7卷 / 07期

关键词：

B-CELL LYMPHOMA; CHEMOTHERAPY; TRANSPLANTATION; RESISTANT; THERAPY;

D O I：

10.1182/bloodadvances.2022008543

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The CORAL study highlighted the need to develop novel salvage regimens in relapsed/ refractory (R/R) diffuse large B-cell lymphoma (DLBCL) previously treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Carfilzomib (CFZ) can overcome rituximab chemotherapy resistance in lymphoma preclinical models by targeting the ubiquitin-proteasome system. We conducted an investigator initiated, single-center, open-label, prospective phase 1 study evaluating the safety and efficacy of CFZ in combination with rituximab, ifosfamide, carboplatin, and etoposide (C-R-ICE) in high-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) eligible patients with R/R DLBCL (NCT01959698). In the dose-escalation phase, 18 patients were enrolled at 6 dose levels with no dose-limiting toxicities noted. CFZ 45 mg/m2 was selected as the recommended dose for expansion. Eleven additional patients were enrolled in the dose-expansion phase. Overall response rate (ORR) was 66% (48% CR; 17% PR); 52% patients underwent HDC-ASCT. An ORR of 85% was observed in patients with nongerminal center B-cell-like (non-GCB) DLBCL compared with only 13% in those with GCB DLBCL. Median progression-free survival (PFS) was 15.2 months (5.1 months, not reached [NR]), and median overall survival (OS) was 22.6 months (6.8 months, NR). 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 GCB subtype. C-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 CFZ into second-line therapy and HDC-ASCT.

引用

页码：1146 / 1155

页数：10

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