The non-GCB subtype of diffuse large B-cell lymphoma(DLBCL) has inferior response to rituximab based chemothrapy. Recent reports show a constitutional expression of NF-κB pathway in non-GCB subtype of DLBCL. Bortezomib, as proteasome inhibitor, has been shown a promising new agent for the treatment of DLBCL. As how the efficacy, doses and protocol of Bortezomib need to be clarified.
This trial is a pilot multicenter clinical study to evaluate the efficacy and safety of an escalated dose of bortezomib based chemotherapy for the treatment of patients with relapsed or refractory non-GCB subtype of DLBCL.
Patients and Materials: A total 24 pts with DLBCL were enrolled in 4 different medical centers. According to Hans' Tissue Microarray (TMA) Classification, 23 pts were diagnosed as non-GCB subtype, and 1 patient have not done the test. 16 pts had relapsed or refractory disease, while 8 pts had fail response to the first line treatment. All the patients had received Rituximab based chemotherapy previously. There were 16 male and 8 female. The patient age ranged from 19 to 73, of which the median age was 55.
All patients were given bortezomib 2.0mg/m2, day 1, I.V. (intravenous injection 12 hours before chemotherapy), 5 pts were given additional dose of 0.7 mg/m2, I.V., at day 8. The combination protocols include: Bortezomib(V)+ICE(G) 13 pts; Bortezomib(V)+HyperCVAD 7 pts; Bortezomib(V)+EPOCH 3 pts; Bortezomib(V)+DHAP 1 pts. The patients were given 1 to 5.courses differently.
The follow-up time were 2 to18 months, with a median time of 8 months. Of 24 pts, 21 evaluable pts received more than 2 courses of therapy: 7 pts achieved complete remission (CR 33.3%), 9 pts achieved partial remission (PR 42.8%), 5 pts had no response (NR 23.8%), The overall response rate (ORR) was 76.1%. Of 16 responsive pts, the PFS were 2 to 18 months; the average PFS was 7.6 months and median PFS was 7.5 months. Up to now, 13 pts were still alive, and 7 pts were dead, and 1 pts lost follow-up. Of 7 death, 5 were caused by disease progression with 4 pts of central nervous infiltrates, 2 were caused by severe infections. The one year overall survival rate (OS) was 65%. Of all the 24 pts, 10 pts had 3 to 4 grade of myelosuppression; 1 case with severe pulmonary infection;1 case with septicemia; 1 case with skin and soft tissue infection; 1 case with fungus infection; 3 cases with herpes zoster infection; 2 cases with skin rashes; 2 cases with hypotension, 1 case with hepatic dysfunction; 1 case with neuralgia.
Our study showed that the escalated dose of bortezomib based chemotherapy had promising response for the treatment of relapsed or refractory non-GCB originated DLBCL. Bortezomib at a single dose of 2.0mg/m2 was safe and tolerable. No acute toxicity or vital adverse events were observed. The relapse of disease in central nervous system as well as infections were relatively common and might need further study.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.