ALBERT

Description: Abstract 2876 Background: HCV infection has been demonstrated to be involved in clonal B cell proliferation and in the subsequent development of non-Hodgkin's lymphoma (NHL). The regression of NHL after antiviral treatment is considered an indirect evidence of this pathogenetic relationship. Aim: to evaluate clinical course of patients affected by HCV infection (serology and HCV RNA positive) and low grade B-cell NHL (LG-NHL), not needing immediate treatment (absence of B symptoms, bulky disease or symptomatic tumor mass and lymphocyte doubling time less than 6 months) and treated upfront with antiviral therapy alone. Method: From 2006 to 2010, 13 patients, affected by LG- NHL at diagnosis have been treated with pegylated interferon (PegIFNa2a, 100–180 mcg weekly) and ribavirin (Rbv, 800–1200 mg daily) for a median treatment period of 6 months (6-18 months). Two patients are still in treatment. M/F ratio was 1.6 and median age was 59 years (range 51–73). The study included 9 marginal zone lymphomas (MZL: 2 splenic MZL, 7 extranodal non gastric MZL), 3 LG-NHL NOS and 1 lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LPL). Cryoglobulin were present in five patients. 7 pts had genotype 2, 5 pts genotype 1b, one not assessed; HCV infection was detected before lymphoma diagnosis in 9 pts and at lymphoma onset in 4 pts. Only 2 patients have previously received other combinations of antiviral therapy. Virologic response was assessed monthly by HCV-RNA polymerase chain reaction (PCR) and hematologic response was evaluated according to International Working Group response criteria (Cheson et al. J Clin Oncol. 2007) at the end of antiviral therapy. Results: Eleven patients completed the planned treatment course. Sustained virologic response (SVR) was achieved in 9 patients (6 with genotype 2); viremia clearance was achieved in a median period of 2 months (1-6). Among patients that gained a SVR, 5 achieved a complete response (CR) (3 genotype 2, 1 1b, one not assessed), one (genotype 2) partial response (PR), and 3 (2 genotype 2 and one genotype 1b) presented stable disease (SD). The remaining patients obtained only a reduction of viremia: one presented a SD and one was in PR. The treatment was well tolerated without any WHO grade III-IV toxicity. Among patients that completed treatment program, more frequent toxicity was haematological (one patient developed a WHO grade 1 anemia and one patients developed WHO grade 1 anemia and grade 2 neutropenia). After a median follow up of 17 months from the end of therapy (range 3–44), considering the 9 patients in SVR, only 2 (1 CR and 1 PR) progressed, maintaining SVR and one lost SVR maintaining SD. Patients that obtained only a reduction of viremia, maintained their hematologic status. Conclusion: We described a high CR rate in patients that obtained SVR after antiviral therapy (55%); the relationship between hematologic and viral response during follow up is not always stringent. We confirm that antiviral therapy could be considered as frontline therapeutic option in cases of HCV-related LG-NHL not requiring immediately immunochemotherapy. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2821 Epidemiological studies demonstrated that HCV is associated with B-cell NHL. A precise prognostication of HCV+ NHL is not available; in particular, the impact of liver toxicity on the outcome of pts treated with (immuno)-chemotherapy is not fully clarified. Aim of the present study was to analyse clinical and virological characteristics, toxicity and prognosis of a large series of indolent and aggressive HCV+ NHL. We studied 1,043 pts with HCV+ NHL diagnosed and treated from January 1993 to December 2009 in 15 italian hematologic institutions; 539 cases were aggressive NHL (522 DLBCL) and 504 indolent NHL (265 MZL). All pts were HIV negative, 3% carried HBsAg and 91% were HCV-RNA+. Thirteen out of 56 HCV-RNA negative pts cleared HCV by means of antiviral therapy before NHL diagnosis. An (immuno)-chemotherapy regimen was administered as first-line treatment in 859 pts: 537 received CHOP-like regimen (+ Rituximab 243), 66 III generation regimen, 174 alkylators, 30 purine analogues, 31 other regimens, 21 R alone. Doses of chemotherapy since first cycle were reduced in 31% of pts. A watch-and-wait policy was adopted in 82 pts, other treatments in 68 pts and anti-HCV antiviral therapy in 34 pts with indolent NHL (12 of whom obtained both a complete virologic and hematologic response). Hepatic toxicity was evaluable in 597 patients: among 347 pts with normal ALT at NHL diagnosis, 52 (15%) developed WHO hepatic toxicity ≥ grade 2; among 250 pts (42%) with abnormal ALT, 26 (11%) experienced ALT increase 〉3.5 times baseline value. Overall, a significant liver toxicity developed in 78 pts (13%) (15% of aggressive NHL and 10% of indolent NHL). Use of Rituximab was not associated with significant liver toxicity (p=0.4); particularly, in DLBCL, R-CHOP and CHOP showed the same rate of significant hepatic toxicity (15%, p=ns), although maximum grade of liver toxicity was registered earlier in patients treated with R-CHOP than in those treated with CHOP (before 3rd cycle respectively in 57% vs 41%, p=0.006). Planned treatment was not completed in 134 pts (29 for liver toxicity). After a median F-UP of 2.6 years, 321 pts died (24 for liver failure). 5-yrs OS was 76% for indolent NHL and 62% for DLBCL. In indolent NHL, the parameters associated with a shorter OS in univariate analysis were: elevated LDH (p