ALBERT

Description: Marginal zone lymphomas (MZLs) are indolent nonfollicular B-cell lymphomas (INFLs) and have heterogeneous clinical behavior. Recently, time to progression of disease at 24 months (POD24) was identified to stratify overall survival (OS) in follicular non-Hodgkin lymphoma and in INFL. Here, we examined the ability of POD24 to predict subsequent OS in a large, international cohort of MZL as part of the NF10 prospective international registry headed by Fondazione Italiana Linfomi (FIL). POD24 was only calculated for MZL patients requiring immediate therapy and was defined as experiencing lymphoma progression within 24 months from diagnosis. Among the 1325 patients enrolled in the NF10 study, we identified 321 patients with MZL for whom immediate therapy was planned right after lymphoma diagnosis. Overall, POD24 was confirmed in 59 patients (18%). Three-year OS for patients with POD24 was 53% with a hazard ratio of 19.5 (95% confidence interval, 8.4-45) compared with patients without POD24 (3-year OS, 95%). Association of POD24 with OS was confirmed for the subgroup of splenic and extranodal MZLs. Assessment of POD24 stratifies subsequent outcome in MZL and identifies a high-risk population. This trial was registered at www.clinicaltrials.gov as #NCT02904577.

Description: Diagnosis of non-CLL B Cell Chronic Lymphoproliferative Disorders (BCLPD), defined by the detection of peripheral blood (PB) B-Cell clone with flow cytometry (FC) Matutesscore≤3, is not an infrequent event in clinical daily practice. Only a portion of these cases may be actually classified according to the 2016 revision of WHO classification of lymphoid neoplasms, as in these cases a non-bone marrow (BM) tissue biopsy is rarely available due to "liquid-only disease" (BM, PB, splenomegaly) or difficult accessible sites. The two most likely diagnosis of BCLPD according to WHO 2016 are splenic marginal-zone lymphoma (SMZL) and monoclonal B Cell lymphocytosis (MBL) with non-CLL phenotype (CD19+, CD20+, SIg+, CD5-), sometimes reported as MZL-like, defined by monotypic clonal B lymphocytes (CBL)

Description: Bendamustine (B) is an alkylating agent with unique chemical structure (purine-like benzimidazole ring) and high cytotoxic activity. In the last decade, the association of B and rituximab (BR) emerged as the worldwide most popular standard treatment of patients (pts) with indolent non-Hodgkin lymphomas (iNHL), in both relapsed/refractory (R/R) and untreated setting. Autologous stem-cell transplant (ASCT) is the standard option in young fit pts with R/R iNHL and has been recently demonstrated to improve survival of follicular lymphoma (FL) pts with early treatment failure (ETF: within 2 years [yrs] of frontline immunochemotherapy [I-CT], Casulo et al, BBMT 2018). The structure similarity with fludarabine, which is associated with a well-known peripheral blood stem cell (PBSC) mobilization impairment, may limit the use of B in younger pts with iNHL potentially candidates for ASCT. Moreover, the effectiveness of CD34+ cells collection in pts treated previously with B is essentially still unknown and based on few small series. We retrospectively analyzed rates of CD34+ cells collection in consecutive pts with iNHL undergoing PBSC mobilization attempt, who had previously received treatment with B (in the same or in a previous line of therapy) in 12 centers of the Fondazione Italiana Linfomi. The primary endpoint was the rate of pts who were able to obtain a successful harvest of PBSC (≥2 x106/Kg of body weight). Overall, we collected complete data about 45 pts with iNHL undergoing PBSC mobilization attempt after previous treatment with B (Table 1). The majority of pts had FL (n=39). Median age at diagnosis was 52 yrs (35-66). Frontline treatments comprised R-CHOP in 27 pts (60%) and BR in 11 (24%). All but 2 pts, who were mobilized during 1st line therapy, experienced disease relapse and initiated 2nd line treatment, including reinduction I-CT, PBSC mobilization and ASCT consolidation. Among pts with FL, 13 (33%) relapsed within 24 months (ETF). Median lines of therapy at PBSC mobilization were 2 (1-4). Eleven pts (24%) received B in 1st line, 29 (65%) as part of 2nd line (n=29, 65%), and 5 (11%) in 3rd or 4th line of therapy. The most frequent mobilization strategy (40 cases, 88%) was CT plus G-CSF (including R-HD-AraC in 27), with "on demand" plerixafor adjunction in 4 cases (10%). Then, two pts (4%) underwent PBSC mobilization with G-CSF only (+ plerixafor in 1) while 3 pts (7%) received G-CSF (+ plerixafor in 1) immediately after a BR course. At first mobilization attempt, 38 out of 45 pts (84%) collected ≥2 x106 CD34+/Kg (Table 2), including 2/2 (100%) in G-CSF only, 35/40 (88%) in CT + G-CSF and 1/3 (33%) in BR cohort (p=0.039), with a median of 1 (1-4) apheresis procedure. Five out of 7 pts who failed first mobilization underwent a second attempt (1 with G-CSF + plerixafor, 3 with CT + G-CSF and 1 with CT + G-CSF + plerixafor) collecting all ≥2 x106 CD34+/Kg. Considering all mobilization attempts, 43/45 pts (96%) reached successful harvest of PBSC (≥2 x106/Kg) and 38/45 (84%) obtained an optimal PBSC collection (≥5 x106/Kg). Median number of PBSC collected was 6.46 x106/kg (3-18). Pre-mobilization bone marrow involvement significantly affected PBSC mobilization (p=0.03), as well as response at mobilization (CR 92%, PR 60%, SD 50%, p=0.02) while cumulative dose of B (〉720 mg/m2, p=0.9) or timing from last B administration (≤3 months, p=0.34) did not. At multivariable analysis, mobilization type (p500/μl and PLT 〉20000/μl: 11 and 13 days). We observed 1 case of MDS (EB-2) and 1 sarcoma after ASCT. At a median follow-up of 6.3 yrs (0.7-14), only 3 pts died (2 for progression and 1 for viral encephalitis), with 8-yrs OS of 89.6% (Fig. 1) and a median PFS from ASCT of 8.1 yrs. Notably, FL pts experiencing ETF did not exhibit worse OS (85.7 vs 87.1% at 8-yrs, p=0.7). High rate of success in PBSC collection reported in this large real-world study supports the evidence that pre-treatment with B does not affect PBSC mobilization in iNHL pts, although we confirmed that B does not display per se a mobilizing capacity. Salvage strategy including ASCT resulted in overall favorable outcome in young pts with R/R iNHL and seemed able to overcome the negative prognostic impact of ETF in FL. Disclosures Luminari: Celgene: Consultancy; Roche: Consultancy; Gilead: Consultancy; Servier: Consultancy; Sandoz: Consultancy. Passamonti:Celgene: Consultancy, Speakers Bureau; Roche: Consultancy; Novartis: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Speakers Bureau.