BACKGROUND: The optimal management of relapsed or refractory aggressive B-cell lymphoma is not standardized. We previously reported the salvage chemotherapy with P-IMVP-16/CBDCA consisting of methylprednisolone (mPSL), carboplatin (CBDCA), etoposide (VP-16), ifosfamide (IFM), and methotrexate (MTX) for patients (pts) with aggressive non-Hodgkin's lymphoma who had previously received CHOP consisting of cyclophosphamide (CPA), doxorubicin (DOX), Vincristine (VCR) and prednisolone (PSL) (Sawada M; Eur J Haematol 2002). The purpose of this study is to determine the efficacy and safety of salvage chemotherapy with rituximab (R) combined with P-IMVP-16/CBDCA (R-P-IMVP-16/CBDCA) for relapsed or refractory aggressive B-cell lymphoma.

PATIENTS AND METHODS: We retrospectively analyzed 66 pts with relapsed or refractory aggressive B-cell lymphoma who had received R-P-IMVP-16/CBDCA (R: 375mg/m2 on day1, mPSL: 1000mg/body on days 2-4, IFM: 1000mg/m2 on days 2-6, MTX: 30mg/m2 on day 4 and 11, VP-16: 80mg/m2 on days 2-4, and CBDCA 300mg/m2 on day 2, with granulocyte colony-stimulating factor every 21 days in 5 institutes of Gifu Hematology Study Group between July 2004 and January 2014. The pts who had responded to R-P-IMVP-16/CBDCA underwent autologous transplantation or received 3 additional R-P-IMVP-16/CBDCA cycles. Pts aged 70 or older were given 75% or less of the standard dose. All patients received R-CHOP or R-THP-COP regimen as a first-line chemotherapy. THP (pirarubicin), a derivative of DOX, is an anthracyclin with less cardiotoxicity than DOX. THP-COP has an equivalent efficacy to CHOP (Turumi H; JCRCO 2004).

RESULTS: Enrolled 66 pts had a median age of 64.5 years [range 25-83] and were 65% male. The pathology of underlying lymphoma comprised diffuse large-B cell lymphoma (n=51), follicular lymphoma grade 3 (n=11), intravascular large B-cell lymphoma (n=1), primary mediastinal B cell lymphoma (n=1) and mantle cell lymphoma (n=2). The response rate [complete response (CR/CRu) plus partial response (PR)] was 60.6% (40/66), including 28 (42.4%) CR/CRu and 12 (18.2%) PR. Another 5 pts had stable disease and 21 pts progressed. Median overall survival (OS) and progression-free survival (PFS) were 47.1 months and 9.2 months, respectively. The OS rate for the 66 pts was 65.1% at 1 yr and 57.3% at 2 yr. The PFS rate for the 66 pts was 45.6% at 1 yr and 31.2% at 2 yr. The survival rate for the 40 responders was 97.4% at 1 yr and 88.1% at 2 yr, and the survival rate for the 26 non-responders was 15.0% at 1 yr (P<0.001). Common toxicity criteria grade ≥ 3 drug-related adverse events included: neutropenia, anemia, thrombocytopenia and febrile neutropenia. Although the major toxicities were neutropenia and febrile neutropenia, only one DLBCL pt with common variable immunodeficiency died of sepsis related to neutropenia. Non-hematological adverse effects were predominantly mild and tolerable.

CONCLUSIONS: The R-P-IMVP-16/CBDCA regimen displayed a significant activity in relapsed or refractory aggressive B-cell lymphoma, with acceptable toxicity and should be considered a candidate for combination chemotherapy. Futher clinical studies should be required.

Figure 1
Figure 1.
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Disclosures

No relevant conflicts of interest to declare.

Topics:
b-lymphocytes, carboplatin, lymphoma, toxic effect, brachial plexus neuritis, chemotherapy regimen, etoposide, neutropenia, cyclophosphamide, doxorubicin, prednisone, and vincristine, febrile neutropenia

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2014 by The American Society of Hematology
2014
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