The Role of Antiviral Treatment in Hepatitis C Virus (HCV)-Related Non-Hodgkin Lymphoma: An Update of a Multicenter Study.

Abstract HCV is largely, although not homogenously, diffuse in North-western Europe and U.S.A. It has been shown to play a role both in hepatocellular carcinoma and in B-cell non-Hodgkin lymphoma (B-NHL). Up to now the exact biological mechanisms that could explain the lymphomagenic role of the virus are unknown. We have previously published a series of 13 patients, affected by low grade B-cell NHL and characterized by an indolent course (i.e. doubling time less than 1 year, no bulky disease), who underwent antiviral treatment only with peghilated interferon and ribavirin (peghilated interferon 50–70 microgram weekly, ribavirin 1000–1200 mg daily). Now we report an update of this study. Up to now we were able to evaluate 16 patients with a mean follow up of 15,1± 7,6 months (range 2–28 months). Eight patients experienced complete or good partial haematological response that has lasted up to now with a mean follow up of 16,5 months, among them 3 splenic marginal lymphomas, 2 nodal marginal, 1 follicular lymphoma, 1 plasmocytoid and 1 marginal extranodal lymphoma. Three other patients achieved a long lasting partial response. The only one relapse (marginal nodal lymphoma) occurred about one year after the end of treatment, hematological relapse happened together with viral relapse, the lymphoma reappeared as highly chemo resistant high grade lymphoma, and two months later the patient died. Interestingly complete and good partial responses were more likely to be seen in viral genotype 2 (p=0.035) and were strictly related to the decrease of viral load under treatment (p=<0.001). Toxicity causes the stop of the treatment in 3 patients; however one of them was able to achieve complete hematological response. Time to achieve hematological response was quite long (mean 8± 4,5 months). This kind of experience strongly provides a role for antiviral treatment in patients affected by HCV related low grade B-cell NHL. Especially viral genotype 2 infection may be considered a good prognostic marker for hematological response as well as decrease of viral load under treatment. Toxicity in our hands was however significant and further experiences are warranted in order to better modulate antiviral therapy doses.

Download Full-text

Antiviral treatment in Hepatitis C Virus (HCV)- related low grade non-Hodgkin lymphoma: An update of a multicenter study

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17526 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17526-17526

Author(s):

D. Vallisa ◽

P. Bernuzzi ◽

A. Lazzaro ◽

E. Trabacchi ◽

A. Arcari ◽

...

Keyword(s):

Viral Load ◽

B Cell ◽

Hodgkin Lymphoma ◽

Antiviral Treatment ◽

Low Grade ◽

Viral Genotype ◽

Non Hodgkin Lymphoma ◽

Hematological Response ◽

Genotype 2

17526 Background: HCV is largely diffuse in North-western Europe and U.S.A. It has been shown to play a role both in hepatocellular carcinoma and in B-cell non-Hodgkin lymphoma (B-NHL). Up to now the exact biological mechanisms that could explain the lymphomagenic role of the virus are under study. Methods: We have previously published a series of 13 patients, affected by low grade B-cell NHL and characterized by an indolent course (i.e. doubling time less than 1 year, no bulky disease), who underwent antiviral treatment only with peghilated interferon and ribavirin (peghilated interferon 50–70 microgram weekly, ribavirin 1000–1200 mg daily). Now we report the second update of this study. Up to now 17 patients are evaluable with a mean follow up of 12.1 ± 8 months (range 2–31 months). Results: Eight patients experienced complete or good partial haematological response that has lasted up to now with a mean follow up of 19,5 months, among them 3 splenic marginal lymphomas, 2 nodal marginal, 1 follicular lymphoma, 1 plasmocytoid and 1 marginal extranodal lymphoma. Three other patients achieved a long lasting partial response. The only one relapse (marginal nodal lymphoma) occurred about one year after the end of treatment, hematological relapse happened together with viral relapse, the lymphoma reappeared as highly chemo resistant high grade lymphoma, and two months later the patient died. Interestingly complete and good partial responses were more likely to be seen in viral genotype 2 (p = 0.04) and were strictly related to the decrease of viral load under treatment (p = 0.005). Toxicity causes the stop of the treatment in 3 patients; however one of them was able to achieve complete hematological response. Time to achieve hematological response was quite long (mean 8 ± 4.5 months). Conclusions: This kind of experience strongly provides a role for antiviral treatment in patients affected by HCV related low grade B-cell NHL. Especially viral genotype 2 infection may be considered a good prognostic marker for hematological response as well as decrease of viral load under treatment. Toxicity in our hands was however significant and further experiences are warranted in order to better modulate antiviral therapy doses. No significant financial relationships to disclose.

Download Full-text

Anti-Lymphoma Activity of Interferon-Free Antiviral Treatment in Patients with Indolent B-Cell Lymphomas Associated with Hepatitis C Virus Infection

Blood ◽

10.1182/blood.v126.23.3938.3938 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3938-3938 ◽

Cited By ~ 4

Author(s):

Luca Arcaini ◽

Caroline Besson ◽

Jan Peveling-Oberhag ◽

Véronique Loustaud-Ratti ◽

Sara Rattotti ◽

...

Keyword(s):

B Cell ◽

Virological Response ◽

Marginal Zone ◽

Antiviral Treatment ◽

Marginal Zone Lymphoma ◽

Hcv Infection ◽

Low Grade ◽

Lymphoplasmacytic Lymphoma ◽

Hematological Response

Abstract Background: The regression of hepatitis C virus (HCV)-associated lymphoma with antiviral treatment (AT) is the strongest argument in favour of an etiological link between lymphoma, especially marginal zone lymphoma (MZL), and HCV infection. In addition, the favourable impact of AT on overall survival of these patients has been reported (Arcaini 2014, Michot 2015). Although there is a clear association across the studies between the lymphoma regression and the clearance of HCV, the direct anti-lymphoma activity of interferon (IFN) cannot be ruled out. AT is undergoing a revolution: new antiviral drugs, including direct-acting antiviral (DAA) like sofosbuvir (SOF) cure more than 90% of infections. However, data on new IFN-free regimens in HCV-associated lymphoproliferative disorders are scanty and based on clinical reports (Rossotti 2015; Sultanik 2015; Carrier 2015). Patients and Methods: We analyzed virological and hematological response of 26 patients (pts) with indolent B-cell non-Hodgkin lymphomas (NHL) or chronic lymphocytic leukemia (CLL) and HCV infection treated with an IFN-free AT. We included the 5 cases reported in literature (Rossotti 2015; Sultanik 2015; Carrier 2015) with updated follow up. Results: Histological, virological and hematological features are summarized in Table 1. Histology distribution was as follows: 12 splenic MZL, 6 extranodal MZL of MALT, 2 leukemic MZL, 2 nodal MZL, 2 CLL/SLL, 1 lymphoplasmacytic lymphoma (LPL) and 1 low grade NHL NOS. Cryoglobulins were present in 13 (symptomatic cryoglobulinemia in 5). HCV genotype was 1 in 15 pts, 2 in 4 pts, 3 in 3 pts and 4 in 2 pts, NA in 2 pts. Three pts previously received chemotherapy and 4 underwent IFN-based therapy before. Twenty-four pts received a SOF-based regimens (SOF + simeprevir in 10, SOF + ribavirin in 5, SOF + daclatasvir in 8, SOF + ledipasvir in 1) and 2 pts other regimens (ombitasvir + paritaprevir + ritonavir + ribavirin and faldaprevir + deleobuvir + ribavirin). In one pt with renal MZL 4 rituximab (R) doses have been added to SOF + simeprevir. Median AT duration was 12 weeks (range: 6-24). At time of present analysis, virological response is available in 21 pts while hematological response has been assessed in 20 pts. A sustained virological response has been obtained in 20 pts; hematological response has been observed only in pts with HCV clearance: in particular 8 pts (all MZL) achieved a complete response and 4 (all MZL) a partial response (comprising one treated also with R) while 5 had stable disease (response by histology is summarized in Table 1). In 7 pts response duration is +1 mo (in 2 pts), +2 mo (in 1 pt), +6 mo (in 3 pts), and +22 mo (in 1 pt); 6 pts (60%) cleared cryoglobulins after AT. After a median follow-up of 6 mo (range: 1-28), 2 pts progressed: one pt shifted to DLBCL and one pt without virological response progressed and died of lymphoma; another pt with hematological CR died of metastatic hepatocellular carcinoma 8 mo after AT. Complete data for all pts will be presented at the meeting. Conclusions: Our study shows that a significant rate of hematological response can be achieved in HCV-associated MZL also with IFN-free AT. These data are a strong rationale for planning prospective trials with DAA in this setting. Table 1. Features of 26 pts with NHL associated with HCV infection treated with IFN-free regimen and lymphoma response by histology N % Age, median (range) 26 57 (40-78) M/F 11/15 42/58 - Marginal-zone lymphoma SplenicNodalExtranodal of MALTLeukemic MZL- CLL - Lymphoplasmacytic lymphoma - Low-grade B-cell NHL NOS 22 12 2 6 2 2 1 1 84.7 46.2 7.7 23.1 7.7 7.7 3.8 3.8 Ann Arbor stage III-IV 19 73 B symptoms 4 15 ECOG 0 1 2 3 11 10 0 1 50 45 0 5 BM involvement 14 54 Extranodal disease 17 65 Splenic involvement 13 50 Liver involvement 5 19 Nodal disease 15 58 Bulky disease 7 27 Leukemic disease 9 35 Elevated LDH 8/22 36 Elevated b2-microglobulin 8/10 80 Albumin <3.5 g/dl 3/21 14 Serum MC 9/22 41 HCV genotype - 1 - 2 - 3 - 4 15 4 3 2 63 17 12 8 Cryoglobulins 13 50 Symptomatic cryoglobulinemia 5/13 38 HBsAg 1/25 4 Anti-HBc 4/25 16 Lymphoma response by histology- Marginal-zone lymphoma (n=17) Splenic (n=9)Nodal (n=1)Extranodal of MALT (n=5)Leukemic MZL (n=2)- CLL (n=2) - Lymphoplasmacytic lymphoma (n=1) CR/PR/SD/Progression 8/4/2/3 4/2/2/1 1/-/-/- 2/1/-/2 1/1/-/- -/-/2/- -/-/1/- Disclosures No relevant conflicts of interest to declare.

Download Full-text

Role of Anti-Hepatitis C Virus (HCV) Treatment in HCV-Related, Low-Grade, B-Cell, Non-Hodgkin's Lymphoma: A Multicenter Italian Experience

Journal of Clinical Oncology ◽

10.1200/jco.2005.06.008 ◽

2005 ◽

Vol 23 (3) ◽

pp. 468-473 ◽

Cited By ~ 174

Author(s):

Daniele Vallisa ◽

Patrizia Bernuzzi ◽

Luca Arcaini ◽

Stefano Sacchi ◽

Vittorio Callea ◽

...

Keyword(s):

Hepatitis C Virus ◽

Hepatitis C ◽

B Cell ◽

Antiviral Treatment ◽

Complete Response ◽

Hcv Infection ◽

Low Grade ◽

Hcv Treatment ◽

Hematologic Response

Purpose Hepatitis C virus (HCV) is endemic in some areas of Northwestern Europe and the United States. HCV has been shown to play a role in the development of both hepatocellular carcinoma and B-cell non-Hodgkin's lymphoma (B-NHL). The biologic mechanisms underlying the lymphomagenic activity of the virus so far are under investigation. In this study, the role of antiviral (anti-HCV) treatment in B-NHL associated with HCV infection is evaluated. Patients and Methods Thirteen patients with histologically proven low-grade B-NHL characterized by an indolent course (ie, doubling time no less than 1 year, no bulky disease) and carrying HCV infection were enrolled on the study. All patients underwent antiviral treatment alone with pegilated interferon and ribavirin. Response assessment took place at 6 and 12 months. Results Of the twelve assessable patients, seven (58%) achieved complete response and two (16%) partial hematologic response at 14.1 ± 9.7 months (range, 2 to 24 months, median follow-up, 14 months), while two had stable disease with only one patient experiencing progression of disease. Hematologic responses (complete and partial, 75%) were highly significantly associated to clearance or decrease in serum HCV viral load following treatment (P = .005). Virologic response was more likely to be seen in HCV genotype 2 (P = .035), while hematologic response did not correlate with the viral genotype. Treatment-related toxicity did not cause discontinuation of therapy in all but two patients, one of whom, however, achieved complete response. Conclusion This experience strongly provides a role for antiviral treatment in patients affected by HCV-related, low-grade, B-cell NHL.

Download Full-text

Randomized Comparison of Cladribine Single (C) or in Combination with Cyclophosphamide (CC), and COP in Previously Untreated Low Grade B-Cell Non-Hodgkin Lymphoma Patients.

Blood ◽

10.1182/blood.v108.11.2481.2481 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2481-2481

Author(s):

E. Kalinka ◽

J. Wajs ◽

K.S. Sulek ◽

M. Blasinska-Morawiec ◽

P. Centkowski ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

Low Grade ◽

Non Hodgkin Lymphoma ◽

Not Otherwise Specified ◽

Ann Arbor ◽

To Receive

Abstract To comparatively assess first-line treatment with cladribine single (C) or in combination with cyclophosphamide (CC), and COP (cyclophosphamide, vincristine, prednisone) in low grade B-cell non-Hodgkin lymphoma (NHL), previously untreated patients (pts) with Ann Arbor stage II-IV were randomly allocated to receive 6 monthly courses of either C, CC, or COP. End points were treatment response, freedom from progression (FFP) and overall survival (OS), and tolerance. From June 1, 2000 to June 30, 2005, 196 pts were randomized in 17 centers. Of 153 pts for whom data is available, 55 (36%) were diagnosed as small lymphocytic, 11 lymphoplasmocytoid (7%), 37 marginal-zone (24%), 42 follicular (27.5%), and 8 not otherwise specified low grade B-cell NHL (5.5%). Randomization constituted comparable groups, including International Prognostic Index variables. Compared to C and CC, COP induced lower overall response rates (75%, 90%, 50%, χ2 =7.9 p<.005), including lower complete remission rates (38%, 62%, 9.5%, χ2=19.2 p<.0001). With a median follow-up of 15 months, FFP was superior in patients receiving cladribine-containing regimens (χ2 = 21.8, log-rank p<.0001). No difference in median OS was observed. Incidences of infections (9% versus 3.5% versus 7%) and non-hematological side effects (7.5% versus 3.5% versus 7%) were similar in the randomized groups, whereas CC but not C induced more frequent peripheral cytopenias compared to COP (30% versus 11%, p=.034). This resulted in higher frequency of prolongation of intervals between CC versus COP treated pts (respectively 45% and 21%, χ2=6.04 p=.014) and C versus CC treated pts (respectively 26% and 45%, χ2=4.24, p=.039). Dose reductions because of hematological or other toxicity were comparable in C (9.5%), CC (20%), and COP (21%) groups. Although final results warrant completed data for all randomised pts with longer follow-up, similar tolerance and higher efficacy of cladribine-based regimens over COP provide rationale to combine C or CC with rituximab in future clinical trials.

Download Full-text

Indolent B-Cell Lymphomas Treated Upfront with Antiviral Therapy: a Series of 13 Patients

Blood ◽

10.1182/blood.v116.21.2876.2876 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2876-2876

Author(s):

Andrea Ferrario ◽

Alessio Aghemo ◽

Maria Cecilia Goldaniga ◽

Michele Merli ◽

Daniele Vincenti ◽

...

Keyword(s):

B Cell ◽

Antiviral Therapy ◽

Virologic Response ◽

Hcv Infection ◽

Hcv Rna ◽

Low Grade ◽

Who Grade ◽

Genotype 1B ◽

Genotype 2

Abstract 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.

Download Full-text

Gender and Race As Prognostic Factors In Patients Treated With Rituximab For B-Cell Non-Hodgkin Lymphoma

Blood ◽

10.1182/blood.v122.21.3053.3053 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3053-3053

Author(s):

Mendel Goldfinger ◽

Santiago Aparo ◽

Krishna Gundabolu ◽

Stefan K Barta

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Medical Center ◽

Multivariate Model ◽

Low Grade ◽

High Grade ◽

Final Multivariate Model ◽

Non Hodgkin Lymphoma ◽

Montefiore Medical

Abstract Introduction The International Prognostic Index (IPI) and the age-adjusted IPI (aaIPI) are the most commonly used tools to predict outcomes in patients with Non-Hodgkin Lymphoma (NHL). The IPI does not take into account sex or race. In the pre-rituximab era, sex was found to be a strong predictor of poor prognosis in low-grade lymphomas. While there is emerging evidence that female sex is associated with better survival in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP, much less is known about the prognostic impact of race. We retrospectively assessed the impact of sex and race on overall survival in patients with indolent and aggressive NHL treated at any stage with rituximab at our institution. Methods We retrospectively identified all patients >/=18 years who were diagnosed with B-cell NHL (except SLL/CLL and Burkitt lymphoma) between 1/1/2000 and 12/31/2010 and received rituximab at any stage as part of their therapy at the Montefiore Medical Center. We collected data on histology, age (<60 vs. >/=60), date of diagnosis, date and status at last follow-up, and stage from the MECCC Cancer registry, and we obtained data on the Charlson Comorbidity Index (CCI) from Clinical Looking Glass® (CLG), an interactive software application developed at Montefiore Medical Center which integrates clinical and administrative datasets. The histological subtypes DLBCL and grade 3 follicular lymphoma (FL) were classified as “high-grade lymphoma” (HGL), while other types of lymphoma were termed “low-grade lymphoma” (LGL; these included marginal zone lymphoma, mantle cell lymphoma, grade 1 & 2 FL, and malignant lymphoma NOS). Self-reported race was classified as White, Black, Hispanic or “Other”. Only <2% of the patients were of “Other” racial background and therefore excluded from this analysis. The primary outcome was overall survival (OS) calculated as time from diagnosis to time of death. We used the Kaplan-Meier (KM) method to describe OS for race and sex and the log-rank test to test for significance (p<0.05). We used a Cox proportional hazard (CPH) model to assess the association of variables with OS. Except for age, race and sex, variables that were not significantly associated with OS (i.e. p-value>0.10 in the multivariate model) were excluded from the final model (backward elimination). Results 353 patients were included in the analysis. Median follow-up for all patients was 37.3 months (range 0.03-202.40). Baseline characteristics between male and females were similar with the exception of age at diagnosis and histology (see Table 1). On univariate analysis there was no OS difference between male and female patients (p=0.13), while race was associated with significant differences in OS (p=0.04; see Fig. 1). In the multivariate model, only stage >/=3 was associated with worse survival (Hazard Ratio [HR] 2.78, 95% CI 1.62-4.77; p<0.0001), but there was no significant association with OS for type of lymphoma (HGL vs. LGL) or the CCI (low vs. high score) and these 2 variables were therefore eliminated from the final multivariate model. In the final multivariate model, female sex was associated with a 37% reduction in the risk of death (HR 0.63; 95%CI 0.40-0.98; p=0.04), while race was no longer associated with OS (Hispanic vs. White: HR 0.76, 95%CI 0.41-1.40, p=0.38; Black vs. White: HR 0.66, 95%CI 0.40-1.10; p=0.11; Black vs. Hispanic: HR 1.15; 95% CI 0.63-2.08, p=0.65). Conclusions Female patients treated at any stage with rituximab for high-grade and low-grade B-cell NHL at our institution experienced longer OS. However, we observed no racial disparity in survival in our analysis. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Efficacy and safety of CAR19/22 T-cell “cocktail” therapy in patients with refractory/relapsed B-cell non-Hodgkin lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2534 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2534-2534

Author(s):

Liang Huang ◽

Na Wang ◽

Chunrui Li ◽

Yi Xiao ◽

Yang Cao ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Hodgkin Lymphoma ◽

Low Grade ◽

Efficacy And Safety ◽

T Cell Therapy ◽

Overall Response ◽

Non Hodgkin Lymphoma ◽

The Impact

2534 Background: Antigen escape relapse has emerged as a major challenge for long-term disease control post CD19-directed therapies, to which dual-targeting of CD19 and CD22 has been proposed as a potential solution. Methods: Between Mar 2016 and Jan 2018, we conducted a pilot study (ChiCTR-OPN-16008526) in 38 patients (pts), who had refractory/relapsed B-cell non-Hodgkin lymphoma (B-NHL), to evaluate the efficacy and safety of sequential infusion of anti-CD19 and anti-CD22, two single-specific, third-generation CAR19/22 T-cell “cocktail”. The cutoff date for data collection was Apr 30, 2018. Results: At a minimum follow-up of 3 months (mos), 26 of the 36 evaluable pts achieved an overall response (ORR), including 18 with a complete response (CR) and 8 with a partial response (PR). The ORR at mo 3 was consistent in different subgroups, irrespective of pathologic subtypes, cell of origin, cytogenetic or genomic aberrations. At the data cutoff, 15 of the 18 pts who had a CR at mo 3 maintained their responses, 2 of 8 pts who had a PR within 3 mos continued to have a CR without additional therapies. Collectively, the best ORR was 83.3%, with a best CR rate of 55.5% and a best PR rate of 27.8%. With a median follow-up of 5.3 mos (range, 0.4 to 16.2), the median PFS was 5.8 mos, and the median OS was not reached (NR). Pts received therapy at first relapse had better PFS than those who received therapy at the time with primary refractory diseases or at multiple relapses. Notably, pts who achieved an overall response at mo 3 (R3m) had significantly extended PFS and OS when compared with pts who did not. Repeated biopsy and IHC was conducted in 3 of the 13 pts. However, loss of CD19 or CD22 was not detected. Of the 9 pts with IgH/MYC translocation, with a median follow-up of 10.1 mos, the median PFS and median OS were NR. At data cutoff, 7 pts who had achieved R3m maintained their responses, including all the 4 pts with double-hit lymphoma. However, of the 10 pts with del(17p) or TP53 mutation, with a median follow-up of 5.3 mos (range, 2.7 to 14.5), the median PFS was 3.6 mos and the median OS was 9.9 mos. All pts experienced reversible CRS, with 21.1% were of high-grade. Neurotoxicity developed in 13.2% pts and were all low-grade. Conclusions: Our results indicated that sequential infusion of CAR19/22 T-cell is efficient and safe for pts with B-NHL. Dual antigen targeting is a promising approach to circumvent antigen loss relapse after CAR T-cell therapy. The impact of genetic subtypes and clinical parameters further underscores the critical importance of personalized immunotherapies. Clinical trial information: ChiCTR-OPN-16008526.

Download Full-text

Hepatitis B Virus Associated B-Cell Non-Hodgkin Lymphoma in Non-Endemic Areas

Blood ◽

10.1182/blood-2018-99-120349 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4228-4228

Author(s):

Marine Lemaitre ◽

Pauline Brice ◽

Marco Frigeni ◽

Catherine Thieblemont ◽

Luca Arcaini ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis B Virus ◽

B Cell ◽

Hbv Infection ◽

Low Grade ◽

Non Hodgkin Lymphoma ◽

B Virus ◽

The World ◽

Endemic Areas

Abstract Introduction Hepatitis B virus (HBV) is a hepatotropic virus accounting for chronic hepatitis and cirrhosis. HBV is also known as oncogenic, leading to increased risks of not only hepatocellular carcinoma but also other cancers including B-cell non-Hodgkin lymphoma (NHL) (Odd-ratio: 1.9-2.0). According to the World Health Organization, 257 million people in the world have an active HBV infection, areas of high prevalence being in Africa, Western Pacific, and Southeast Asia. While some studies were performed in endemic area, little is known concerning the characteristics of HBV-related NHL in Occident. Moreover, although the need for antivirals to prevent HBV reactivation is well known in patients with HBV receiving chemo or immunotherapy, their impact on their prognosis is unknown. Our aim is to describe the characteristics and outcomes of patients with NHL and active HBV in non-endemic areas. Methods Thirty-nine consecutive patients diagnosed with active HBV infection and B-cell NHL between 2002 and 2017 were enrolled retrospectively in France and Italy. Active HBV infection was defined by positive antigen HbS (AgHbs) and/or positive HBV-DNA in serum. HCV or HIV positive patients were excluded. Their characteristics and outcomes were analyzed and, for Diffuse Large B-cell Lymphoma (DLBCL), compared with those of HBV-negative patients enrolled in R-CHOP arms of LYSA trials. Results Most patients were men (29/39), and median age at NHL diagnosis was 59 years ranging from 29 to 88 years. Twenty-two patients (57%) were born in Europe, 13 in Africa (33%), 4 in Asia (10%). Thirty-three patients had positive AgHbs and 28, positive viral load. The histological subtype distribution was: 23 (59%) DLBCL; 13 low-grade NHL (LG-NHL) including 4 follicular lymphoma (FL), 3 spleen marginal zone lymphoma (SMZL), 3 mucosa associated lymphoid tissue lymphoma and 3 not otherwise specified LG-NHL; 2 mantle cell and one Burkitt lymphoma. Of note, none of the primary DLBCL had a low-grade component but 2 FL and one LG-NHL transformed to DLBCL during follow-up. Five patients had a monoclonal immunoglobulin component. Overall, 26 patients (67%) had an extra-nodal involvement (bone marrow (10), liver (8), digestive (6), and bone (5)). All but one DLBCL patients were treated with R-CHOP/R-CHOP-like regimen leading to complete remission in 19 out of 22 (84%). Treatment of LG-NHL patients was diverse: Rituximab monotherapy, immuno-chemotherapy (R-CHOP, R-Chlorambucil, R-Bendamustine), corticosteroids alone or with radiotherapy, Helicobacter pylori treatment or wait and watch. After front-line therapy, 20 DLBCL patients (87%) and 9 LG-NHL (69%) patients achieved complete remission (CR). Thirty-six patients received antiviral treatment following NHL diagnosis while 3 did not (one DLBCL, 2 LG-NHL). Seven patients (18%) died during follow-up: 4 due to progression of lymphoma (3 DLBCL and one LG-NHL), 2 to hepatocellular carcinoma, one to infection. Median overall survival was 81 months without difference between DLBCL and LG-NHL patients. Lastly, the comparison of the outcomes of the 23 DLBCL patients with those of HBV-negative patients did not show significant difference. Conclusions To our knowledge, this is the first study exploring HBV-related NHL in non-endemic areas. Interestingly, more than 40% of patients were born in high-endemic areas. The strong predominance of DLBCL (59%) is concordant with studies performed in high-incidence areas. Strikingly, it contrasts with the peculiar distribution of HCV-related NHL supporting that some different pathophysiological mechanisms contribute to NHL in HBV. However, as in HCV-related NHL, frequent hepatic or digestive involvement raises the hypothesis of home privileged lymphomagenesis favored by viral induced inflammation or by infection of B-cells. No difference was detected when comparing HBV DLBCL outcomes with non HBV patients. Remarkably, all patients, except one, received antiviral therapy combined with chemotherapy. In endemic areas, while some studies reported that patients with HBV NHL had a poorer prognostic, others suggested that antivirals could overcome this pejorative impact. This study, performed in Western Europe, area of low HBV prevalence, underlines the predominance of DLBCL among patients with active HBV infection and the similar outcomes of DLBCL patients to non-HBV patients when treated with a combination of R-CHOP and antivirals. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Randomized Multicenter Trial of Cladribine Alone (C) or in Combination with Cyclophosphamide (CC), and COP in Previously Untreated Low Grade B-Cell Non-Hodgkin Lymphoma Patients: The First Interim Analysis.

Blood ◽

10.1182/blood.v104.11.3305.3305 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3305-3305 ◽

Cited By ~ 1

Author(s):

Ewa E. Kalinka ◽

Jaroslaw J. Wajs ◽

Kazimierz Sulek ◽

Tadeusz Robak ◽

Maria Blasinska-Morawiec ◽

...

Keyword(s):

B Cell ◽

Hodgkin Lymphoma ◽

Interim Analysis ◽

Response Rates ◽

Rank Test ◽

Low Grade ◽

First Line ◽

Non Hodgkin Lymphoma ◽

Log Rank Test

Abstract To comparatively assess first-line treatment with cladribine alone (C) or in combination with cyclophosphamide (CC), and COP (cyclophosphamide, vincristine, prednisone) in low grade B-cell non-Hodgkin lymphoma (NHL), previously untreated patients (pts) with Ann Arbor stage II–IV were randomly allocated to receive 6 monthly courses of either C, CC, or COP. End points were treatment response, freedom from progression (FFP) and overall survival (OS), and tolerance. From June 1, 2000, 165 pts were randomized in 17 centers. The first interim analysis performed at July 1, 2004 included 105 out of 165 randomized pts (63.6%) who have completed at least six cycles of the scheduled chemotherapy. Of 105 analyzed pts, 38 (36.2%) were diagnosed as small lymphocytic, lymphoplasmocytoid 8 (7.6%), marginal-zone 22 (21%), follicular 33 (31.4%), and not otherwise specified low grade B-cell NHL 4 (3.8%). Randomization constituted comparable groups, including international Prognostic Index variables. Compared to C and CC, COP induced lower overall response rates (75%, 85%, 51%, χ2 test p<.005), including lower complete remission rates (43%, 62.5%, 5.5%, χ2 test p<.001). With a median follow-up of 10 months, median FFP was superior in patients receiving cladribine containing regimens (8 versus 11 versus 6 months, respectively, χ2= 15.1, log-rank test p<.001). No difference in median OS was detected (9 versus 12 versus 7 months, respectively, χ2= 1.15, log-rank test p=.56). Incidences of infections (7% versus 15% versus 11%) and non-hematological side effects (7% versus 7.5% versus 16%) were similar in the randomize groups, whereas CC but not C induced more frequent cytopenias compared to COP (30% versus 11%, χ2 test p<.05). This resulted in more frequent intervals’ prolongation between CC versus COP cycles (respectively 32.5% and 11%, χ2 test p<.05) but dose reductions because of hematological or other toxicity were comparable in C, CC, and COP groups (11% versus 17.5% versus 5.5%). In pts with low grade B-cell NHL, first line C and CC regimens provided similar response rates, FFP, and OS, which were superior to those obtained with COP. The first interim analysis has resulted in discontinuation of accrual in the COP arm. An observed trend toward a better tolerance of C over CC, which may influence the choice between these regimens as front-line treatments, warrants larger number of pts and longer follow-up.

Download Full-text

Primary MALT Type Skin Lymphoma—Is ‘Wait and See’ a Possible Strategy?

Clinical medicine Oncology ◽

10.4137/cmo.s336 ◽

2008 ◽

Vol 2 ◽

pp. CMO.S336

Author(s):

Florentina Silvia Delli ◽

Thomas Zaraboukas ◽

Ioanna Mandekou-Lefaki

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Skin Lesions ◽

Low Grade ◽

Non Hodgkin Lymphoma ◽

Cutaneous Lymphomas ◽

Wait And See ◽

Cutaneous B Cell Lymphoma

Primary cutaneous lymphomas are the second most common site of extranodal non-Hodgkin lymphoma. A specifically type named extranodal marginal zone B-cell lymphomas are indolent low-grade neoplasma. We report a case of a 42-year-old white man with multiple subcutaneous tumors located on the trunk and neck. The histopathological exam showed a non-epidermotropic, dense lymphocytic infiltrate. Histologic, immunohistochemical and cytologenetic analysis diagnosed primary cutaneous B-cell lymphoma MALT type. Investigation for other extranodal MALT lymphoma gastrointestinal tract, lung, salivary and thyroid glands was negative. The patient refused radiotherapy, but he accepted every 6 months close follow-up. Over a seven years period, we noticed a progressively disappearance of the skin lesions. The necessity of aggressive treatment of this disease with excellent prognosis is discussed. The treatment necessity of primary cutaneous B-cell lymphoma MALT type is discussed.

Download Full-text