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In: Blood, American Society of Hematology, Vol. 140, No. Supplement 1 ( 2022-11-15), p. 3603-3605

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2022-166535

Language: English

Publisher: American Society of Hematology

Publication Date: 2022

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: British Journal of Haematology, Wiley, Vol. 167, No. 5 ( 2014-12), p. 718-720

Type of Medium: Online Resource

ISSN: 0007-1048 , 1365-2141

URL: Issue

URL: Article

DOI: 10.1111/bjh.2014.167.issue-5

DOI: 10.1111/bjh.13052

Language: English

Publisher: Wiley

Publication Date: 2014

detail.hit.zdb_id: 1475751-5

In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 124-124

Abstract: Introduction Limited stage follicular lymphoma (FL) is usually managed with involved field radiotherapy (IFRT), although different approaches are currently carried out, ranging from watch and wait to combined treatment. RT on involved lymph nodes allows eradication of the disease only in 40-50% of patients. Anti-CD20 monoclonal antibodies (MoAb), widely used in advanced stage FL, are likely to be effective in reducing the relapse risk, although no scientific evidence of their role has been provided. The aim of this multicenter phase II prospective study was to evaluate the role of MRD in identifying patients unlikely to be cured by RT, for whom an immunotherapy-based consolidation could improve outcome. Methods 110 patients with stage I/II FL were enrolled. IFRT was administered to all patients at a dose of 24 Gy. Peripheral blood (PB) and bone marrow (BM) samples were centralized to the Italian FIL (Federazione Italiani Linfomi) MRD Network of EuroMRD-certified laboratories: the presence of a BCL2/IGH rearrangement was investigated at baseline in all patients by nested PCR (NEST) and RQ-PCR (RQ), the latter according to the EuroMRD guidelines. In patients BCL2/IGH+ at baseline by both NEST and RQ in BM and/or PB, MRD was analyzed in both tissues after IFRT and every 6 months over a three-year follow-up period. Patients with positive MRD by both NEST and RQ in BM and/or PB after IFRT or who became positive during the follow-up were treated with 8 weekly doses of the anti-CD20 MoAb ofatumumab. The primary objective of the study was to define the efficacy of immunotherapy in obtaining the disappearance of BCL2/IGH rearranged cells. Results Preliminary data are available for 107 patients, 57 males, 50 females. Median age was 55 years (29-83). 17% had G1 FL, 32% G2, 40% G3A, 11% NOS. The FLIPI score was 0 in 59% of patients, 1 in 35%, 2 in 6%. 69% of patients had inguinal site involvement. Despite a negative BM biopsy, at baseline 30% of patients (n=32) had a BCL2/IGH rearrangement (30 MBR, 1 MBR and mcr, 1 mcr) in the BM and/or PB; the concordance between compartments was 90%, with 10% of negative PB showing a positive BM. No significant differences were observed in relapse probability between patients with or without a molecular marker. All patients were submitted to IFRT and all obtained a clinical response, which was complete in 79 of the 101 evaluated patients (78%) and partial in 22 (22%). MRD evaluation after treatment revealed the persistence of BCL2/IGH rearranged cells in the PB and/or BM in 60% of patients. According to the design of the protocol, MRD-positive patients, either after IFRT (n=18) or in case of conversion to a positive signal during the follow-up (n=7), received 8 weekly administration of ofatumumab. A conversion to MRD negativity, evaluated in 23 treated patients, was obtained in 20 (87% - CI 65.1-97.1). This result was significantly superior to the expected 50%. One death occurred after IFRT, due to ischemic stroke. Adverse events likely correlated to ofatumumab occurred in 7/25 treated patients, consisting of infusion reactions in 5, leading to a permanent interruption of immunotherapy in 3. After a median follow-up of 18 months, all patients who achieved a MRD negativity with ofatumumab underwent a regular molecular follow-up and are still MRD-negative. Overall, clinical relapse or progression were observed in 17 patients: 13 (18%) among the 73 "no marker" patients; 2 relapses (16%) were observed among the 12 MRD-negative patients after IFRT and 2 relapses were observed among the 23 patients treated with the anti-CD20 MoAb (8.7%), 1 having achieved a MRD negativity and 1 not. No significant differences in event-free survival have so far been observed between the three groups. Conclusions The MRD data of this phase II trial for early stage FL indicate that RT alone is often insufficient to eradicate the disease, being capable of inducing a negative MRD only in 40% of evaluable cases, with a long-lasting effect only in half of them. The primary objective of this study - MRD negativity after immunotherapy - was achieved, obtaining the disappearance of BCL2/IGH rearranged cells in the majority of patients treated with ofatumumab. The strategy of an immunotherapy consolidation after IFRT in MRD-positive patients allowed to increase molecular responses. A longer follow-up and further studies on larger patient populations will allow to conclusively define the impact of this MRD-driven strategy also on clinical outcome. Disclosures Pulsoni: Roche: Consultancy, Speakers Bureau; Takeda: Consultancy; Pfizer: Consultancy; Sandoz: Consultancy; Gilead: Speakers Bureau; Merk: Consultancy; Bristol Meyer Squibb: Speakers Bureau. Ferrero:Servier: Speakers Bureau; EUSA Pharma: Membership on an entity's Board of Directors or advisory committees; Gilead: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Luminari:ROCHE: Other: Role as Advisor ; CELGENE: Other: Role as Advisor & Travel Grant; TAKEDA: Other: Travel Grant; GILEAD: Other: Lecturer . Liberati:Amgen: Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Celgene: Honoraria, Other: Clinical trial support; Bristol-Myers Squibb: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy; Janssen: Honoraria; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Clinical trial support; Roche: Other: Clinical trial support; Novartis: Other: Clinical trial support. Ferreri:Roche: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Kite: Consultancy. Nassi:Takeda: Consultancy; Janssen: Consultancy; Merck: Consultancy. Corradini:Roche: Honoraria; Novartis: Honoraria; kite: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria. Mannina:Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees. Arcaini:Celgene: Speakers Bureau; Gilead Sciences: Research Funding; Bayer, Celgene, Gilead Sciences, Roche, Sandoz, Janssen-Cilag, VERASTEM: Consultancy; Celgene, Roche, Janssen-Cilag, Gilead: Other: Travel expenses. Galimberti:Roche: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau. Ladetto:AbbVie: Honoraria; Roche: Honoraria; ADC Therapeutics: Honoraria; Acerta: Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; J & J: Honoraria; Celgene: Honoraria. Foà:Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Roche: Consultancy, Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Celltrion: Membership on an entity's Board of Directors or advisory committees; Amgen Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: The anti-CD20 MoAb Ofatumomab is employed to eradicate Minimal Residual Disease in early stage Follicular Lymphoma(FL). The drug is registered for Chronic Lymphocytic Leukemia, not for FL.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2019-123106

Language: English

Publisher: American Society of Hematology

Publication Date: 2019

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e20073-e20073

Abstract: e20073 Background: Early stage follicular lymphoma (FL) is usually managed with involved field radiotherapy (IFRT), allowing eradication of the disease in 40-50% of patients (pts). The aim of this multicenter phase II prospective study was to evaluate the role of minimal residual disease (MRD) in identifying pts unlikely to be cured by IFRT, for whom an immunotherapy-based consolidation could improve outcome. Methods: 110 pts with stage I/II FL were enrolled and treated with 24 Gy IFRT. Peripheral blood (PB) and bone marrow (BM) samples were centralized to the FIL (Federazione Italiani Linfomi) MRD Network of EuroMRD-certified laboratories. In BCL2/IGH+ pts at baseline, MRD was analyzed by nested PCR (NEST) and RQ-PCR (RQ) in BM and/or PB after IFRT and every 6 months over a 3-year period. Pts with positive MRD by both NEST and RQ in the BM and/or PB after IFRT or who became positive during the follow-up (FU) were treated with 8 weekly doses of the anti-CD20 MoAb ofatumumab (OFA). Primary objective: efficacy of immunotherapy in obtaining a negative MRD. Results: 49 of 106 pts were males. Median age was 55 y (29-83). 69% of pts had inguinal involvement. At baseline, 30% of pts had a BCL2/IGH rearrangement (30 MBR, 1 MBR and mcr, 1 mcr) in BM and/or PB; the concordance between compartments was 90%. All pts obtained a clinical response after IFRT, with persistence of BCL2/IGH+ cells in PB and/or BM in 60% of cases. MRD-positive pts, either after IFRT (n = 18) or in case of conversion to a positive signal during the FU (n = 7), received OFA, obtaining a conversion to MRD negativity, in 20/22 cases (91% - CI 65.1-97.1), significantly superior to the expected 50%. After a median FU of 25 months, all but 2 pts who achieved a negative MRD with OFA are still negative. A clinical relapse or progression was observed in 17 pts: 13 (18%) among the 73 “no marker” pts; 2 relapses (16%) were observed among the 12 MRD-negative pts after IFRT and 2 among the 25 treated with OFA (8%), 1 having achieved a MRD negativity and 1 not. No significant differences in PFS have so far been observed between the three groups. Conclusions: In early stage FL RT alone is often insufficient to eradicate the disease, inducing a negative MRD only in 40% of pts, long-lasting only in half of them. The primary objective of this study - MRD negativity after immunotherapy - was achieved. The strategy of an immunotherapy consolidation after IFRT in MRD-positive pts allowed to increase molecular responses. A longer FU and further studies will allow to define the impact of this MRD-driven strategy also on clinical outcome. Clinical trial information: EudraCT number: 2012-001676-11 .

Type of Medium: Online Resource

ISSN: 0732-183X , 1527-7755

URL: Article

DOI: 10.1200/JCO.2020.38.15_suppl.e20073

Language: English

Publisher: American Society of Clinical Oncology (ASCO)

Publication Date: 2020

detail.hit.zdb_id: 2005181-5

In: Blood, American Society of Hematology, Vol. 118, No. 21 ( 2011-11-18), p. 3680-3680

Abstract: Abstract 3680 In B-cell malignancies, biased usage of immunoglobulin heavy chain variable (IGHV) genes and stereotyped clusters of immunoglobulin receptor suggest that a limited set of antigens or superantigens are involved in malignant transformation. In the present study we analyzed the IGH rearrangements of a large series of patients with Waldenström Macroglobulinemia (WM), IgM-monoclonal gammopathies of undetermined significance (IgM-MGUS) and IgM-related disorders (IgM-RD), with the aim to characterize IGH repertoire and to search for clusters of stereotyped receptors. A total of 123 patients with IgM monoclonal gammopathies, including 59 WM, 55 IgM-MGUS and 9 IgM-RD underwent IGHV amplification and direct sequencing. The median age of patients was 63 years (range: 32–86). Diagnosis of WM, IgM-MGUS and IgM-RD was made according to the consensus criteria proposed at the 2nd International Workshop on WM. All IGHV-D-J rearrangements were analyzed using the IMGT databases and the IMGT/V-QUEST tool to identify HCDR3 aminoacid (AA) sequences. HCDR3 sequences were aligned with each other and compared to 28,400 HCDR3 sequences from public databases (EMBL, NCBI, IMGT/LIGM-DB) and from unpublished multi-laboratory databases. Alignments were performed using the multiple sequence alignment software ClustalX (2.0). Criteria for including sequences in a cluster were: 〉 60% aminoacid identity, IGHV gene belonging to the same clan, identical HCDR3 length and same junction residues and/or same IGHD-J genes. A productive monoclonal IGHV-D-J rearrangement was obtained in 99/123 patients, including 55 WM, 37 IgM-MGUS and 7 IgM-RD. IGHV genes were mutated in 94/99 patients (95%). The median somatic hypermutation rate was 93.3% (range 85.5%-97.9%). Four cases showed 〉 98% identity with the germline sequences, whereas one single WM sample showed 100% identity with the germline sequence. When compared with the normal mature B-cell repertoire, a significant over-representation of the IGHV3 family and a significant under-representation of the IGHV1 and IGHV4 families were observed both in WM (87%, 7% and 2% respectively) and in IgM-MGUS (78%, 8% and 8% respectively). IGHV3-23 was the gene most commonly used (29%). Analysis of IGHV3-23 sequences for AA changes in the positions involved in superantigen recognition by IGHV3 subgroup genes showed that the majority of cases had two or more non-permissive AA changes that compromise the capacity to mediate superantigen recognition and binding. The frequency of novel N-glycosylation sites, introduced by the somatic hypermutation process, in this series of patients (12%) was not statistically different from that observed in normal memory B-cells, suggesting that WM, IgM-MGUS and IgM-RD cells do not need to interact with stromal GC environmental elements. The median HCDR3 length was 13 AA (range: 5–29) and was similar in WM, IgM-MGUS and IgM-RD. Intra-WM/IgM-MGUS/IgM-RD search for HCDR3 similarity showed no association that met minimal requirements to define stereotyped receptors. The comparison of WM/IgM-MGUS/IgM-RD sequences with non WM/IgM-MGUS/IgM-RD database showed that WM/IgM-MGUS/IgM-RD sequences are unrelated to known CLL or SMZL subsets. Only one IgM-MGUS occurring in a HCV-positive patient formed a novel subset with other 4 HCV-related lymphoproliferative disorders. The findings of this analysis of WM, IgM-MGUS and IgM-RD IGH sequences indicate that: i) family-usage in the WM, IgM-MGUS and IgM-RD showed a skewed usage compared to normal B-cell repertoire; ii) WM, IgM-MGUS and IgM-RD-specific HCDR3 clusters do not occur to a frequency detectable with currently available databases; iii) WM, IgM-MGUS and IgM-RD sequences are not related to known CLL and SMZL HCDR3 clusters; iv) one IgM-MGUS showed similarities with sequences derived from pathological HCV-related lymphoproliferations, suggesting that, at least in a fraction of cases, HCV may have a pathogenetic role. For the large majority of IgM-related disorders, however, there is little evidence in favor of a B-cell receptor-driven pathogenesis. Disclosures: No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V118.21.3680.3680

Language: English

Publisher: American Society of Hematology

Publication Date: 2011

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3938-3938

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.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.3938.3938

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 2026-2026

Abstract: Bakground. The association of light chain (AL) amyloidosis with lymphoplasmacytic lymphoma/Waldenström's Macroglobulinemia is well established. However, both localized and systemic AL amyloidosis have been also reported in other types of lymphoma, but a detailed description of these cases is still lacking. Methods. We systematically searched the database of 1,415 newly diagnosed consecutive patients (pts) with AL amyloidosis of the Pavia Amyloidosis Research and Treatment Center for pts with non-lymphoplasmacytic lymphoma and AL amyloidosis, and identified 34 pts diagnosed between 2004 and 2018. Results. Seventeen pts (50%) had a diagnosis of marginal zone lymphoma (MZL), mainly extranodal MZL (EMZL). Median age at the time of lymphoma diagnosis was 65 years (45-81) and 23 pts (68%) were males. An autoimmune disease was documented in 8 pts (24%), with Sjögren Syndrome as the commonest type. Clinical characteristics of pts according to type of lymphoma (MZL vs non-MZL) and type of AL (systemic vs localized) are presented in Tables 1 and 2. The amyloid deposits were characterized as AL-type by immunoelectron microscopy or mass spectrometry in all cases. Twelve pts (35%) had a concomitant diagnosis of AL (within 12 months before or after the diagnosis of lymphoma). In 2 cases the diagnosis of lymphoma occurred after 16 and 45 months from diagnosis of AL, respectively. In 20 pts (10 MZLs), the lymphoma was diagnosed a median time of 58.6 months (range: 13.6-320.8 months) before AL diagnosis: all but 1 of these cases were treated for the underlying lymphoma and 16 of them had a complete remission at the time of AL diagnosis. Twenty-nine pts (85%) had positive serum and/or urine immunofixation and/or an abnormal free light chains ratio (FLCR), while 5 pts had no detectable monoclonal component (MC) and normal FLCR: these pts developed only localized AL amyloidosis. Localized AL was documented in 10 pts (29%), 7 of them had a MZL. Involved organs were represented by MALT sites (6 nodular pulmonary, 1 tracheobronchial, 2 skin, 1 bladder). Eleven pts with systemic AL amyloidosis died for progression of amyloidosis and 1 because of gastric cancer, while no patient with localized AL died during follow-up. The median overall survival (OS) from the diagnosis of AL amyloidosis was 42.5 months (Fig.1). Conclusions. In our series collected in a referral center, MZL is the most common non-lymphoplasmacytic lymphoma that associates with AL amyloidosis. Hematologists should be aware that MZL is associated not only with localized light chain deposition at the lymphoma site, but also with systemic AL amyloidosis. Systemic AL amyloidosis could be itself an indication to start a specific treatment for the lymphoproliferative disease, even in otherwise asymptomatic lymphomas. The presence of a MC and elevated FLC are clues for systemic AL amyloidosis. Figure 1. Figure 1. Disclosures Merlini: Prothena: Consultancy; Janssen: Consultancy; Ionis: Consultancy; Millenium: Consultancy; Akcea: Consultancy; Pfizer: Consultancy. Palladini:Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Other: Travel support; Prothena: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-118161

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 3933-3933

Abstract: Background: Histologic transformation (HT) refers to a biologic event leading to the development of a high grade non-Hodgkin lymphoma, mostly diffuse large B cell lymphoma (DLBCL), in patients (pts) with an underlying follicular lymphoma (FL), whose recently reported risk is 2% to 3% per year. The prognosis of t-FL has been considered historically very poor, but several studies in the Rituximab (RTX) era suggest that survival may be more favorable than previously recognized. The treatment approach for t-FL is often individualized and pts are generally excluded from clinical trials, so there is a paucity of objective data on the optimal management of t-FL, which still represents an unmet need. The aim of our survey conducted in a large number of pts with histologically confirmed t-FL observed in 9 FIL Centers was to analyze the clinical factors and the different treatment strategies which can predict post-transformation outcome. Methods: One hundred seventy-seven t-FL were retrospectively selected from Institutional datasets; the inclusion time frame was from 2002 to 2014. All Histologic Transformations (HT) were biopsy confirmed. Response assessment was made as recommended by International Workshop criteria. Survival analysis were performed with Kaplan-Meier method and compared by Log-Rank test. Results: T-FL occurred at initial diagnosis (Group 1) in 93 cases (53%): 52 were DLBCL (29%) evolving from a prior FL, 31 (17%) composite lymphoma and 10 (6%) discordant lymphoma. HT occurred after a previous FL diagnosis (Group 2) in 84 pts (47%): 15 pts (8%) were treatment-naïve at HT (Group 2A), 38 pts (21%) transformed at first relapse or progression (Group 2B) and 31 (18%) experienced late HT (Group 2C). Median age at HT was 60 years (range: 20-83). No differences were found between Group 1 and 2 and between Group 2A, 2B and 2C in term of clinical features (age, disease stage, B-symptoms). Group 1 received CHOP/CHOP-like regimens in 75% of pts. RTX was used with chemotherapy (CT) in 92% of pts and in 22% as maintenance. Autologous Stem Cell Transplantation (ASCT) was delivered as consolidation in 14%. Group 2 received CHOP/CHOP-like regimens in 39% of pts, platinum-containing regimens in 14%, high dose sequential therapy in 32%. RTX was added to CT in 71% of cases; 12% received RTX maintenance and 23% ASCT consolidation. CHOP as CT and RTX maintenance were used more often in Group 1 pts. Overall Response Rate (ORR) for Group 1 was 94%, with 77 pts (83%) achieving Complete Response (CR) and 10 (11%) Partial Response (PR).With a median follow-up of 43 months, 5-yr Progression-Free Survival (PFS) and Overall Survival (OS) were 60% and 83%, respectively. ORR for Group 2 was 57%, with 43 pts (51%) obtaining CR and 5 (6%) PR; focusing on the subgroups 2A, 2B, 2C ORR was 80%, 63% and 39%, respectively (p 0.017). The 5-yr OS was 52%, statistically inferior to Group 1 (p 〈 0.001) (Figure 1). The use of RTX with CT and of consolidation ASCT favourably influenced survival only in group 2 but not in group 1 pts in univariate analysis. Survival showed a significant trend (p 〈 0.001) to progressively worsen from Group 1 to Group2c pts (Figure 2). Moreover, considering the number of previous FL treatment lines received by group 2, 5-yr OS was 58% for pts who received 1-2 lines compared to 20% for pts who received 〉 2 lines (p=0.004) (Figure 3). Conclusion: Outcome of t-FL in the RTX era confirms to be better than reported in historical series and strongly differs among subgroups of pts according to the time of transformation and to the number of pre-HT treatment lines. Pts with FL transformation at lymphoma diagnosis, including composite and discordant cases, or with FL transforming after an initial watch and wait policy, i.e. treatment-naïve, show an excellent outcome with standard immuno-chemotherapy, comparable to that of FL (Federico JCO 2013) and of de novo DLBCL (Cunningham, Lancet Onc 2013). They probably do not benefit from front-line ASCT consolidation. Both ORR and survival are significantly worse in pts with t-FL diagnosed after being treated for FL. However t-FL diagnosed at first relapse/progression in this study obtained a 5-ys OS of 51%, which compares favorably with historical cohorts. On the other hand late transformation has an inferior outcome, which becomes really dismal in the sub-group of pts who transformed after two previous lines for FL, whose median survival is less than one year and clearly represent an unmet clinical need. Disclosures Rusconi: Roche: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.3933.3933

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 116, No. 21 ( 2010-11-19), p. 2876-2876

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.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V116.21.2876.2876

Language: English

Publisher: American Society of Hematology

Publication Date: 2010

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: American Journal of Hematology, Wiley, Vol. 96, No. 6 ( 2021-06)

Type of Medium: Online Resource

ISSN: 0361-8609 , 1096-8652

URL: Issue

URL: Article

DOI: 10.1002/ajh.v96.6

DOI: 10.1002/ajh.26167

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 1492749-4