ALBERT

Description: Abstract 3707 Poster Board III-643 Introduction response to salvage chemotherapy prior to high–dose therapy (HDT) is of major prognostic concern in relapsed/refractory HL. FDG-PET is able to distinguish between persistent disease and fibrosis/necrosis and has thus become the mainstay to define clinical response in this setting (Cheson et al, JCO 2007). The value of FDG-PET in this subset of patient is less well established. IGEV chemotherapy has shown very encouraging results as induction therapy in refractory/relapsed HL (Santoro et al, Haematologica 2007). Aims to retrospectively evaluate the predictive value of PET in pts with relapsed/refractory HL receiving IGEV and HDT. Methods seventy-two multicentric cases with refractory/relapsed HL who had completed IGEV x 4 courses and HDT between 01/98 and 05/07 were reviewed. FDG-PET evaluation was performed before HDT and, according to revised Cheson criteria, complete remission (CR) was defined as negative FDG-PET, independently from the presence of residual masses at CT scan. Univariate analysis was performed considering FDG-PET as well as other usually evaluated prognostic factors. Results patient characteristics: M/F 30/42, median age 33 (range 16-71), Nodular sclerosis 61 (85%), refractory 28 (39%), relapsed 44 (61%), one previous regimen 60 (83%), B symptoms 18 (25%), bulky disease 7 (10%), extranodal disease 32 (44%), previous radiotherapy 39 (54%). After induction, 36 pts (50%) received single (with BEAM as conditioning regimen ), and 36 (50%) tandem HDT (with melphalan as first and BEAM as second conditioning). After IGEV, on the basis of PET 47 pts (65%) were classified as complete remission (CR), 21 (29%) as partial remission (PR) and 4 (6%) did not respond. Ten of the 47 PET negative pts, and 18 of the 25 PET positive pts relapsed. With a median follow up 48 months, the 3-year PFS was 80% vs 25% for patient with negative vs positive PET respectively (HR 5.7 no CR vs CR - CI 95%: 2.6-12.4). The 3-year overall survival (OS) was 91% vs 56 % for patient with negative vs positive PET respectively (HR 7.8 no CR vs CR CI 95%: 2.6-23.7). In univariate analysis, factors influencing the probability of achieving CR to IGEV were disease status (refractory vs relapse) (p.096) and bulky disease at IGEV (p .088). Factor significantly associated with PFS and OS are reported in table. In multivariate analysis only response to therapy, as defined by pre-transplant PET result, maintained significance as prognostic indicator for both PFS (HR 5.7) and OS (HR 7.8). Conclusions these data in homogeneously treated pts with refractory/relapsed HL underline the crucial prognostic relevance of pre-transplant FDG-PET, even overwhelming the impact of disease status at progression. FDG-PET driven trials are highly recommended in this subset of patients. Disclosures: No relevant conflicts of interest to declare.

Description: INTRODUCTION: high-dose chemotherapy (HDC) followed by autologous hematopoietic stem cell transplantation (ASCT) is a curative option for relapsed diffuse large B-cell lymphoma (DLBCL). However, relapse within 1 year after diagnosis, previous therapy with rituximab and secondary IPI = 2 or 3 have been associated with unsatisfactory outcome even after ASCT, thus the better treatment of these patients is matter of debate and efforts are ongoing in order to improve survival. METHODS: on a total of 146 DLBCL patients receiving ASCT, we identified 78 adult patients who had responsive but still measurable disease after first-line therapy or relapsed/progressive disease with one or more adverse features as specified above. All patients were 〉18 years old and received ASCT at our institution. Patients were grouped according to the administered treatment: 1) n= 21 patients were in response but not in complete remission (CR) after first-line and received HDC and ASCT; 2) n= 48 patients had refractory or relapsed disease and received salvage chemotherapy followed by HDC and ASCT (n=46 single ASCT, n=2 double ASCT); 3) n=9 patients received salvage therapy then tandem autologous-allogeneic SCT due to the presence of any of the above mentioned adverse features. For all patients, salvage chemotherapy was mostly VIHA or DHAP with the addition of rituximab. Most used regimens of HDC were Melphalan 200 mg/mq or BEAM. Among the nine patients undergoing tandem auto-allo, eight received Melphalan 200 mg/mq and one BEAM; allogeneic donors were either HLA-identical siblings (n=3), unrelated (n=1) or haploidentical ones (n=5). All conditioning regimens before allogeneic SCT were reduced-intensity or nonmyeloablative. RESULTS: at last follow-up, survival rate is 57% for group 1 (12 alive out of 21 patients), 27% for group 2 (13/48) and 67% for group 3 (6/9). Cause of death in this last group was disease relapse/progression for all 3 cases (2 patients were in partial remission (PR) before allo, 1 in CR). Disease status before allogeneic SCT for the 6 alive patients was CR (n=3) and PR (n=3). Their follow-up is +8, +24, +26, +40, +45 and +70 months since ASCT. Of note, survival rate was 74% for the 47 patients receiving HDC and ASCT in first CR (candidated upfront to ASCT due to high-risk IPI at diagnosis) and 62% for the 21 relapsed patients who did not present any of the above mentioned adverse features at relapse. Those two groups were taken from the same initial sample of 146 patients. CONCLUSION: for patients affected by relapsed DLBCL with one or more adverse prognostic features, administration of allogeneic SCT after ASCT as a tandem strategy provides promising results compared with patients receiving ASCT alone and deserves further investigation, especially taking into account the rapid expansion of platforms using T-cell replete haploidentical grafts. Upfront HDC followed by ASCT appears to be a valid option for those patients in PR after first-line therapy, with a 57% survival rate in our series. Disclosures No relevant conflicts of interest to declare.

Description: Abstract 1645 Background: Indolent non follicular B-Cell Lymphomas (INFL) are an eterogenous group of lymphomas and include small lymphocityic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), and marginal zone lymphoma (MZL). Relapsed INFLs in advanced stage have a relatively poor prognosis, with low complete response to conventional chemotherapy and short survival. Lenalidomide (R®) is an immunomodulatory drug with effects on the innate immune system that may enhance antibody-dependent cell mediated cytotoxicity as well as the development of specific anti-tumor immune responses. These immunologic effects may synergize with the action of rituximab (R). To test the efficacy of R® combined with R (R2), we have conducted a multi center, open label phase II clinical trial in patients (pts) with relapsed INFL. Methods: Eligible pts must have indolent non follicular B-cell lymphoma relapsed after at least 2 but less than 4 prior lines of R-containing immuno-chemotherapy with measurable disease. Patients received oral R® 20 mg once daily on days 1–21. R is administered at a dose of 375 mg/m2 at day 14 of every course. Treatment is repeated every 28 days for up to 6 courses. The primary objectives of the study were to evaluate the antitumor activity of oral R® when given in combination with R and to assess the safety of R2 evaluated by standard criteria (CTC-NCI 3.0). The secondary objectives were progression free survival (PFS), event free survival (EFS) and duration of remission (DR). Results: From July 2010 and June 2012, 39 patients were enrolled: 19 had SLL, 11 had LPL, 4 splenic MZL, 3 extranodal MZL and a 2 nodal MZL. Median age was 68 years (51–76) and 58% were male. LDH value was increased in 17% of pts and β-2-microglobulin in 87%; 41% of pts had Hb

Description: Abstract 1213 Poster Board I-235 INTRODUCTION: Patients with relapse or refractory Hodgkin Lymphoma (HL) still have a poor prognosis. High dose chemotherapy (HDCT) with autologous stem cells transplant (ASCT) is the gold standard, while about 40-60% of patients treated can achieve a durable remission. Complete remission (CR) to salvage therapy is the issue for a better outcome after ASCT. IGEV chemotherapy is now emerging as the most powerful salvage scheme in terms of CR achieved, safety and stem cells mobilization. Tandem high dose chemotherapy and ASCT has been already reported as experimental approach in several non randomized studies which demonstrate its feasibility and low toxicity. AIM: To investigate the efficacy in term of FFP and OS of : To investigate the efficacy in term of FFP and OS of tandem high dose chemotherapy with ASCT compared to a single procedure, in the setting of HL patients which are in complete remission after IGEV. METHODS: From November 1997 to May 2007 121 patients were enrolled in a prospective trial with IGEV plus high dose chemotherapy with single or tandem ASCT. : From November 1997 to May 2007 121 patients were enrolled in a prospective trial with IGEV plus high dose chemotherapy with single or tandem ASCT. RESULTS: After IGEV, 56 patients reached complete remission. Main clinical characteristics: M/F: 30/26; median age: 31 years (15-70); refractory/relapsed: 18/38; median prior regimens: 1 (1-2); prior radiotherapy: 35; 〈 3/ 〉3 involved sites: 41/15. Of them 20 received a single procedure with BEAM whereas 36 received tandem ASCT (Melphalan 200 mg/m2 followed by BEAM within 3 months). No significant characterists emerged in the two populations in a match analysis. In our intention to treat analysis patients which received a single transplant have a relapse risk 3.3% higher than tandem group(C.I. 95%. 1.6.10; p value: 0.025). When we analyzed the program fulfilled, relapse risk was 2.13% higher ( C.I. 95%. 1.05, 4.34; p value: 0.035). No differences were seen in the OS, probably due to the eterogeneous salvage programs. : After IGEV, 56 patients reached complete remission. Main clinical characteristics: M/F: 30/26; median age: 31 years (15-70); refractory/relapsed: 18/38; median prior regimens: 1 (1-2); prior radiotherapy: 35; 〈 3/ 〉3 involved sites: 41/15. Of them 20 received a single procedure with BEAM whereas 36 received tandem ASCT (Melphalan 200 mg/m followed by BEAM within 3 months). No significant characterists emerged in the two populations in a match analysis. In our intention to treat analysis patients which received a single transplant have a relapse risk 3.3% higher than tandem group(C.I. 95%. 1.6.10; p value: 0.025). When we analyzed the program fulfilled, relapse risk was 2.13% higher ( C.I. 95%. 1.05, 4.34; p value: 0.035). No differences were seen in the OS, probably due to the eterogeneous salvage programs. CONCLUSION: Our data show the benefit of tandem ASCT in complete responders to IGEV salvage chemotherapy, in terms of FFP in a multivariate analysis, in patients with relapse or refractory HL. Furthermore, a randomized trial comparing tandem ASCT to a single course of ASCT after induction therapy could definitively demonstrate its usefulness. : Our data show the benefit of tandem ASCT in complete responders to IGEV salvage chemotherapy, in terms of FFP in a multivariate analysis, in patients with relapse or refractory HL. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Anti-PD-1 monoclonal antibodies (mAbs) are highly active in relapsed/refractory classical Hodgkin lymphoma (cHL), but most patients (pts) will still relapse. Given this, allogeneic stem cell transplantation (alloHSCT) remains an important option for pts after PD-1 blockade, as it offers the possibility of cure. Prior reports have suggested that alloHSCT after PD-1 mAbs may be associated with severe immune-related complications including acute graft-versus-host disease (GVHD), veno-occlusive disease (VOD) and cytokine release/febrile non-infectious syndrome (CRS). Prior studies of alloHSCT after PD-1 blockade in cHL have been limited by the small number of pts and short follow-up, preventing an accurate assessment of long-term outcomes and complications, risk factors for early toxicity, and the impact of transplant strategies such as choice of GVHD prophylaxis. We therefore assembled a large retrospective international cohort of cHL pts who underwent alloHSCT after PD-(L)1 blockade to better answer these questions, including an assessment of the impact of post-transplant cyclophosphamide (PTCy) on efficacy and toxicity. Methods: Medical records and databases were reviewed at 26 European and United States transplant centers to identify pts with cHL who underwent an alloHSCT any time after receiving a PD-1 or PD-L1 mAb. Response assessment was performed by local investigators according to Lugano 2014 criteria. Overall survival (OS), progression-free survival (PFS), cumulative incidence (CumInc) of relapse (CIR), non-relapse mortality (NRM), acute (a) and chronic (c) GVHD were estimated, as was the association between baseline variables and these outcomes. Results: Between 2014 and 2019, 150 pts were identified who underwent alloHSCT after a median of 10 (range, 1-74) doses of nivolumab (n=118), pembrolizumab (n=31), or avelumab (n=1). The median age was 31 (range 17-68) and pts had received a median of 4 (range, 2-11) lines of therapy prior to PD-(L)1 blockade. 138 pts (92%) had failed BV and 111 (74%) autologous HSCT. The best overall response to PD-(L)1 mAbs was CR for 62 pts (41%), PR for 55 (37%), SD for 17 (11%), PD for 15 (10%) and unknown for 1 (1%). Median time from last dose of PD-(L)1 mAb to alloHSCT was 80 days (range, 17-756) with 70 pts (47%) receiving intervening systemic therapy. At alloHSCT, 90 pts were in CR (60%), 45 in PR (30%), 5 in SD (3%), and 10 in PD (7%). Donors were haploidentical (n=71, 47%), matched sibling (n=29, 19%), matched unrelated (n=39, 26%), mismatched unrelated (n=7, 5%), cord blood (n=2, 1%), or unknown (n=2, 1%). Stem cell source was bone marrow (n=38, 25%), peripheral blood (n=110, 73%), or cord blood (n=2, 1%). GVHD prophylaxis included PTCy in 88 pts (59%) (69/71 (97%) with haploidentical donors; 19/79 (24%) with other donors). With a median post-alloHSCT follow-up for survivors of 23.8 months (range, 1-67), the 2y OS and PFS were 79% (95CI 71-86%) and 65% (95CI 55-73%), respectively, while the 2y CumIncs of relapse and NRM were 21% (95CI 13-29%) and 14%, (95CI, 8-22%), respectively (Fig. 1A-B). 27 pts have died, 3 due to disease and 24 to NRM, including aGVHD (n=7) and VOD (n=2). Veno-occlusive disease (VOD) occurred in 5 pts (day 100 CumInc 4%) and 29 pts (19%) developed CRS (grade 1 n=16; grade 2 n=7; grade 3 n=4; grade 4 n=2). The 6-month CumIncs of grade 2-4, grade 3-4 and grade 4 aGVHD were 39%, 16% and 8%, respectively. Hyperacute GVHD (onset ≤ 14 days after alloHSCT) occurred in 4% of pts and was fatal in 2 pts. The 2y CumInc of cGVHD was 45%. Neither receipt of 〉 10 doses (median) of anti-PD-(L)1 mAb nor undergoing alloHSCT ≤80 days (median) after last dose of PD-(L)1 mAb were associated with PFS or OS. However, pts with a shorter time to transplant (≤80 days) appeared to have a higher risk of severe (grade 3-4) aGVHD (6m CumInc 24% vs 9%, p=0.006). Recipients of PTCy in this cohort had lower 2y CumIncs of cGVHD (34% vs 58%, p=0.01) and relapse (12% vs 31%, p=0.02), superior 2y PFS (76% vs 54%, p=0.015), and similar rates of severe aGVHD (15% vs 18%, p=0.5), 2y NRM (12% vs 16%, p=0.5), and 2y OS (82% vs 78%, p=0.6). Conclusions: With extended follow-up of a large international cohort, our results argue that alloSCT performed after PD-(L)1 mAbs is a feasible strategy associated with an excellent PFS and a very low CIR for this disease. The use of PT-Cy appears to be associated with improved outcomes and may at present represent the optimal transplant strategy in this pt population. Figure Disclosures Corradini: kite: Honoraria; Abbvie: Honoraria; Servier: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Roche: Honoraria; Novartis: Honoraria; KiowaKirin: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Ho:Jazz Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Consultancy; Omeros Corporation: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Kite: Consultancy, Other: advisory board, Research Funding; Novartis: Consultancy, Other: advisory board, Research Funding; Juno: Consultancy, Other: advisory board; Unum Therapeutics Inc.: Research Funding. Herrera:Adaptive Biotechnologies: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Gilead Sciences: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; AstraZeneca: Research Funding; Merck: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Kite Pharma: Consultancy, Research Funding. Blaise:Jazz Pharmaceuticals: Honoraria; Sanofi: Honoraria; Pierre Fabre medicaments: Honoraria; Molmed: Consultancy, Honoraria. Hamadani:Pharmacyclics: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Merck: Research Funding; Otsuka: Research Funding; Janssen: Consultancy; Medimmune: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Takeda: Research Funding; Celgene: Consultancy. Ansell:LAM Therapeutics: Research Funding; Affimed: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Affimed: Research Funding; LAM Therapeutics: Research Funding; Mayo Clinic Rochester: Employment; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Affimed: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Bristol-Myers Squibb: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding. Nieto:Astra-Zeneca: Research Funding; Affimed: Consultancy; Affimed: Research Funding; Novartis: Research Funding. Feldman:Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Pfizer: Research Funding; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Eisai: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Viracta: Research Funding; Trillium: Research Funding; Roche: Research Funding; Takeda: Honoraria, Speakers Bureau. McGuirk:ArticulateScience LLC: Other: Assistance with manuscript preparation; Bellicum Pharmaceuticals: Research Funding; Kite Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Gamida Cell: Research Funding; Pluristem Ltd: Research Funding; Juno Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Novartis: Research Funding; Fresenius Biotech: Research Funding. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding. Stamatoulas Bastard:Celgene: Honoraria; Takeda: Consultancy. Houot:Bristol Myers Squibb: Honoraria; Merck Sharp Dohme: Honoraria. Manson:Bristol Myers Squibb: Honoraria. Orvain:Incyte: Honoraria; Novartis: Honoraria; Jazz Pharmaceuticals: Other: Travel & accommodations; Pfizer: Other: Travel & accommodations. Bouabdallah:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Frigault:Novartis: Consultancy; Kite/Gilead: Honoraria; Nkarta: Consultancy; Incyte: Consultancy; Juno/Celgene: Consultancy; Foundation Medicine: Consultancy; Xenetic: Consultancy. Chen:Takeda: Consultancy; Kiadis: Consultancy; Magenta: Consultancy; Abbvie: Consultancy; Incyte: Consultancy. Lynch:T.G. Therapeutics: Research Funding; Rhizen Pharmaceuticals S.A: Research Funding; Takeda Pharmaceuticals: Research Funding; Juno Therapeutics: Research Funding; Incyte Corporation: Research Funding; Johnson Graffe Keay Moniz & Wick LLP: Consultancy. Smith:AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharp & Dohme Corp: Consultancy, Research Funding; Acerta Pharma BV: Research Funding; Portola Pharmaceuticals: Research Funding; Pharmacyclics: Research Funding; Bristol-Myers Squibb (spouse): Research Funding; Denovo Biopharma: Research Funding; Genentech: Research Funding; Ignyta (spouse): Research Funding; Incyte Corporation: Research Funding; Ayala (spouse): Research Funding; Seattle Genetics: Research Funding. Byrne:Karyopharm: Research Funding. Cohen:Hutchison: Research Funding; Astra Zeneca: Research Funding; Janssen Pharmaceuticals: Consultancy; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Takeda Pharmaceuticals North America, Inc.: Research Funding; Gilead/Kite: Consultancy; Genentech, Inc.: Consultancy, Research Funding; UNUM: Research Funding; ASH: Research Funding; LAM Therapeutics: Research Funding; Lymphoma Research Foundation: Research Funding. Svoboda:AstraZeneca: Consultancy; Celgene: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; Kyowa: Consultancy; Merck: Research Funding; BMS: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding. Santoro:Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Servier: Consultancy, Speakers Bureau; Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Speakers Bureau; BMS: Consultancy; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau. Armand:Sigma Tau: Research Funding; Otsuka: Research Funding; Pfizer: Consultancy; ADC Therapeutics: Consultancy; Tensha: Research Funding; Affimed: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Adaptive: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Infinity: Consultancy; Genentech: Research Funding. Zinzani:Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau. Carlo-Stella:Servier: Consultancy, Honoraria, Other: Travel, accommodations; Genenta Science srl: Consultancy; Boehringer Ingelheim: Consultancy; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Sanofi: Consultancy, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; AstraZeneca: Honoraria; Janssen Oncology: Honoraria; MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Takeda: Other: Travel, accommodations.

Description: Background Advanced-stage, relapsed indolent non follicular lymphomas (INFLs) have a relatively poor prognosis, with low complete response to conventional chemotherapy and short survival. Thus, there is a need for innovative treatment with high efficacy and a good safety profile. Lenalidomide (R®) is an immunomodulatory drug with a direct tumoricidal effect and action on T, NK and stromal cells that may enhance antibody-dependent cell mediated cytotoxicity as well as the development of specific anti-tumor immune responses. These immunologic effects may synergize with the action of rituximab (R). To test the efficacy of R® combined with R (R2), we have conducted a multi center, open label phase II clinical trial in patients (pts) with relapsed INFL. Methods Eligible pts must have indolent non follicular B-cell lymphoma relapsed after at least 2 but less than 4 prior lines of R-containing immuno-chemotherapy with measurable disease. Patients received oral R® 20 mg once daily on days 1-21. R is administered at a dose of 375 mg/m2 at day 14 of every course. Treatment is repeated every 28 days for up to 6 courses. The primary objectives of the study were to evaluate the antitumor activity of oral R® when given in combination with R and to assess the safety of R2 regimen evaluated by standard criteria (CTC-NCI 3.0). The secondary objectives were the evaluation of progression free survival (PFS) and overall survival (OS). Results From July 2010 and March 2013, 44 pts entered the protocol. Six out of 44 pts were excluded from this analysis as 2 withdrew informed consent and 4 refused to start treatment immediately after signing the informed consent. Enrolled pts (38 cases) had: 18 small lymphocytic lymphoma (SLL), 12 lymphoplasmacytic lymphoma (LPL) and 8 marginal zone lymphoma (MZL). Median age was 68 years (51-75) and 58% were male. LDH value was increased in 21% of pts and β-2-microglobulin in 75%; 51% of pts had Hb

Description: Abstract 2674 Aim FDG positron emission tomography (PET) is the mainstay of response evaluation in some lymphoma subgroups such as DLBCL or HL according to Cheson criteria 2007. Due to its indolent behaviour, PET restaging has been poorly explored in Follicular Lymphoma (FL) Methods: The analysis was retrospectively conducted in pts with FL who underwent whole-body 18F-FDG-PET as part of response evaluation at the end of first line or savage treatment program at our institution from August 2001 to June 2010. Results: Seventy five patients were identified. Main clinical characteristics: median age 58 (range 26– 78); male 37 pts; B symptoms 6 pts; bulky disease 5 pts; stage IV 42 pts; bone marrow involvement 32 pts. Fifty-five pts were evaluated after first line treatment program, while 20 pts after salvage therapy program. Main chemotherapy regimen: CHOP or CHOP-like 38, CVP 11, polichemotherapy containing high-dose cytosine-arabinoside 11, fludarabine containing regimens 4. Furthermore, 19 pts underwent autologous peripheral stem-cell transplantation after either first line or salvage therapy. Eleven pts also received consolidation radiotherapy. Forty-two pts received Rituximab during chemotherapy. At the end of treatment, 54 pts reached complete remission as confirmed by PET. With a median follow-up of 53 months, a significantly lower actuarial 4yr PFS was observed in post-treatment PET+ versus. PET- patients: 35.1% vs. 74.8% (log rank p

Description: Introduction: RP6530 is a novel, next generation, highly specific dual PI3K δ/γ inhibitor with nano-molar inhibitory potency. Preliminary results demonstrated acceptable safety profile and anti-tumour activity in patients (pts) with advanced hematologic malignancies (ASH 2015). Herein we present the final analysis from a Phase 1 study of RP6530 (NCT02017613). Methods: This was a standard 3+3 dose escalation study in pts with relapsed or refractory hematologic malignancies having ECOG performance status (PS) ≤2, measurable/evaluable disease, and life expectancy of at least 12 weeks. Endpoints were safety, pharmacokinetic (PK), pharmacodynamics (PD) and efficacy [overall response rate (ORR), complete response (CR), partial response (PR)]. RP6530 was given orally twice/thrice daily in 28-day cycles until disease progression, unacceptable toxicity, or withdrawal from the study. Results: Thirty-five pts (median age 54 years; range: 20-83; 22 males) were enrolled across various dose levels (25-1200 mg BID and 600-800 mg TID). Pts were highly pre-treated [median prior therapy: 6 (range: 1-13)], had a good PS (ECOG 0/1/2 recorded in 29/3/3 cases, respectively) and 26 (74.2%) were refractory to last therapy. Unlike studies with other PI3k inhibitors, recruitment was limited to aggressive NHL (e.g. DLBCL, MCL, and PTCL) and HL with very few pts of CLL and indolent diseases. Majority (74%) had stage 3/4 disease. RP6530 was well tolerated with no DLT up to the dose of 1200 mg BID and 800 mg TID. The median duration of therapy was 2.78 cycles (range: 0.28-19 cycles). Majority of AEs were mild and resolved with/without concomitant medication. None of grade 3/4 AEs or SAEs were deemed related to RP6530, except four Grade 3 events [hypertriglyceridemia (n=1), neutropenia (n=2) and diarrhea (n=1)]. No drug related elevated ALT/AST, colitis or pneumonia was observed. None of the pts were withdrawn or dose reduction required due to related AEs/SAEs. Thirty pts were evaluated for responses. Single agent activity was noticed at ≥ 200 mg BID. The ORR was 20% (95% CI: 08-36%), including 2 CR (7%) and 4 PR (13%), with a disease control rate (CR+PR+SD) of 60%. Responding pts included HL (n=4), PTCL (n=1) and DLBCL (n=1). Median duration of response was 6 cycles (3.5-19 cycles). Clinical response (CR/ PR) were associated with a progressive reduction in pAKT expression in circulating lymphocytes as early as two hours after the first dose and peaked on Day 8 when the median percentage of pAKT+ lymphocytes was reduced by 44%. PK demonstrated dose-proportional increase in plasma concentrations. Conclusions: RP6530 was well tolerated with no DLT and a promising clinical activity in pts with advanced, heavily pre-treated relapsed/refractory hematologic malignancies. Phase II studies are recommended to evaluate anti-tumor activity at an optimal dose of 800 mg BID. Safety profile further supports combination therapy with existing/novel targeted agents, given the very low incidence of toxicity with RP6530. Disclosures Carlo-Stella: Boehringer Ingelheim: Consultancy; Rhizen Pharmaceuticals: Research Funding. Barde:Rhizen Pharmaceuticals SA: Employment. Kumar:Rhizen Pharmaceuticals SA: Employment. Viswanadha:Incozen Therapeutics: Employment.

Description: Introduction: Previous studies indicate that follicular lymphoma patients who have progression of disease (POD) within 24 months (ie POD24) of receiving frontline chemoimmunotherapy have worse overall survival and thus constitute a high-risk population (Casulo et al. J Clin Oncol 33:2516-2522, 2015; Jurinovic et al., Blood 128:1112-1120, 2016). We have previously reported in the CHRONOS-1 study in patients with relapsed or refractory indolent B-cell lymphoma that treatment with the pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor copanlisib resulted in durable responses with a manageable safety profile (Dreyling et al., J Clin Oncol 35:3898-3905, 2017). We explore here the outcomes for the subset of patients with rapid POD from the CHRONOS-1 study. Methods: Patients with histologically confirmed indolent B-cell non-Hodgkin lymphoma and relapsed after, or refractory to, ≥2 prior lines of treatment were eligible. Previous treatment had to include rituximab (R) and an alkylating agent or regimen. Copanlisib was administered at a fixed dose of 60 mg via 1-hour I.V. infusion on days 1, 8 and 15 of a 28-day cycle. Treatment continued until progression or unacceptable toxicity. The primary efficacy endpoint was objective response rate after ≥4 cycles as assessed per independent radiologic review (Cheson et al., JCO 20:579, 2007). Secondary efficacy endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Adverse events (AEs) were reported using MedDRA (version 19.1). This exploratory analysis was based on patient's first-line treatment. Results: A total of 140 patients were treated and evaluable for POD based on first-line treatment; the principal histologies were follicular lymphoma (FL; n=102) and marginal zone lymphoma (n=23). First-line treatments in 140 evaluable patients included: 34% R-CHOP, 23% R-other, 21% R-CVP, 18% chemotherapy, and 2% patients R only. For FL patients, 87 of 102 (85%) received some form of R-chemotherapy as first-line treatment. A total of 93 patients (66.4%) progressed in less than 24 months and were deemed the POD24. The median time from 1st line treatment to first POD was 11.0 months in the POD24 group. The median number of lines of prior therapy for both groups was 3. The median time to progression for the most recent line of therapy prior to start of copanlisib treatment was also shorter for the POD24 group (15.7 months; 48.9% refractory). At the time of data cutoff (February 2018), the median duration of copanlisib treatment was 6.0 months (range 0.2-44.2) for the POD24. Whereas the fraction of patients with complete responses (CR) were identical in both groups (17%) [Table], the ORR was 58.1% in the POD24 group. In FL patients the ORR was similar in both groups, but the percent of patients with CR was higher in the POD24 group (17.7%). The overall median DOR was 14.9 months and 14.1 months, respectively. Median PFS was 11.3 months in the POD24 group; approximately 50% censored events in each group. Median OS was 42.6 months in the POD24 group. The median duration of safety follow-up was 6.7 months in the POD24 group. All-grade treatment-emergent adverse events (AEs) were similar in both groups, with grade (G) 3/4 events 48.4%/33.3% in the POD24 group. Serious AEs considered treatment-related occurred in 29.3% of patients (15.0% G3/7.1% G4). There were 3 treatment-related G5 events, 2 (2.2%) in the POD24 group. Conclusions: Two-thirds of patients treated with copanlisib in the CHRONOS-1 study were considered high-risk based on POD in less than 24 months after first-line therapy, yet the efficacy of copanlisib in both groups was similar. These results suggest that copanlisib treatment should be explored as treatment for patients failing to achieve durable responses in the first-line setting. Disclosures Leppa: Roche: Consultancy, Honoraria, Research Funding; Bayer: Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy; Janssen: Consultancy, Research Funding. Follows:Abbvie: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees. Lenz:Gilead: Consultancy, Honoraria; Celgene Corp.: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding, Speakers Bureau; Novartis: Research Funding; Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, Accomodations, Expenses, Research Funding, Speakers Bureau. Demeter:Amgen: Consultancy; BMS: Consultancy; Novartis: Consultancy; Aramis Pharma: Consultancy; Pfizer: Consultancy; Roche: Consultancy; Angelini: Consultancy. Rodrigues:Bayer: Employment. Wirtz:Bayer: Employment. Hiemeyer:Bayer: Employment. Liu:Bayer: Employment. Koechert:Bayer: Employment. Garcia-Vargas:Bayer: Employment. Childs:Bayer: Employment. Zinzani:PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Dreyling:Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sandoz: Membership on an entity's Board of Directors or advisory committees.

Description: Introduction: Phase 1/2 trials using the programmed cell death-1 (PD-1) checkpoint inhibitors Nivolumab and Pembrolizumab in relapsed/refractory classic Hodgkin lymphoma (R/R cHL) who had failed autologous-SCT (Auto-SCT) showed high response rates and durable responses in the majority of patients. However, with extended follow-up, progression-free survival (PFS) curves from the CheckMate 205 trial failed to show a plateau, thus suggesting the need for a consolidation therapy in cHL responding to anti-PD-1. Reported here is the retrospective analysis of the outcome of 34 cHL patients who received an Allo-SCT after treatment with PD-1 inhibitors. Patients and Methods: From Nov 2014 to Apr 2017, 44 R/R cHL enrolled in the CA209-205, CA209-254 and MK3475087trials(median age, 31 years; range, 18-81) received nivolumab (n=42) or pembrolizumab (n=2) until complete remission (CR), very good partial remission (PR) defined as a tumor burden reduction 〉80%, or progressive disease (PD).At study entry, 30 patients (84%) had refractory disease, 39 (89%) had failed BV and 38 (86%) Auto-SCT. Tumor assessment was performed according to Cheson et al (JCO, 2014). Non-relapse mortality (NRM) was defined as death by any reason other than disease progression. Cumulative incidence of relapse, NRM, and graft-versus-host disease (GVHD) was assessed using the Kaplan-Meier method. Results: After a median duration of anti-PD-1 therapy of 10 months (range, 3-33), 18 patients (41%) experienced CR or PR whereas 26 (59%) progressed. Sixteen of 18 responding patients were allografted. Eighteen of 26 patients who progressed during anti-PD-1 therapy received additional chemotherapy and were finally allografted. Overall, 34 of 44 patients were allografted. Allografting was not performed due to age (n=1), PD (n=4), patient refusal (n=5). The median time from last nivolumab to Allo-SCT was 49 days (range, 23 - 372). At Allo-SCT, 22 patients (65%) were in CR, 11 (32%) in PR and 1 (3%) in PD. Donors were haploidentical sibling (n=23), matched sibling (n=5), or matched unrelated (n=6). Stem cell source was bone marrow (n=15) and peripheral blood (n=19).Acute graft-versus-host disease (aGVHD) was recorded in 15 patients.The cumulative incidence (CI) of grade 2-4 and grade 3-4 aGVHD at 100 days was 46% and 12%, respectively; the 2-year CI of cGVHD was 27%. Non-infectious complications including febrile syndrome, macrophage activation syndrome and cytokine release syndrome, as well as infectious complications occurring until day +100 post-allografting are detailed in a companion abstract.With a median follow-up of 18 months (range, 1.8-39.3), one patient died due to relapse and 5 to non-relapse mortality (NRM) [(acute Graft-versus-Host Disease (aGVHD) (n=1), CMV pneumonia (n=1), immune-mediated pneumonia (n=1) heart failure (n=1), post-transplant lymphoproliferative disorder (PTLD) (n=1)]. The 2-year cumulative incidence (CI) of relapse and NRM was 3.1% and 19.7%, respectively. The 2-year OS and PFS were 76% and 76%, respectively. Conclusions: With an extended follow-up, data reported herein clearly show that Allo-SCT performed after PD-1 inhibitors or the sequence PD-1 inhibitors/chemotherapy is a feasible consolidation strategy associated with an unprecedented low relapse incidence. Early transplant-related complications prompt at identification and implementation of risk-minimizing strategies. PD-1 inhibitors eventually combined with salvage chemotherapy and Allo-SCT represent a paradigm shift in the treatment of refractory cHL. Disclosures Carlo-Stella: Boehringher Ingelheim Italia: Consultancy; Sanofi: Consultancy; MSD Italia: Speakers Bureau; Amgen: Speakers Bureau; Janssen: Speakers Bureau; ADC Therapeutics: Research Funding, Speakers Bureau; AstraZeneca: Speakers Bureau; Genenta Science: Speakers Bureau; Rhizen Pharmaceuticals: Research Funding; Bristol-Myers Squibb: Speakers Bureau.