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Background/aim To study the long-term clinical efficacy and tolerability of ibrutinib monotherapy in real-world relapsed and refractory chronic lymphocytic leukemia (RR-CLL) patients outside clinical trials. Patients and methods Clinical data of 171 RR-CLL patients treated with ibrutinib were collected within the observational study of the Polish Adult Leukemia Study Group. Results Median patient age was 64 years. Patients were pretreated with 3 (1-10) median lines of therapy, while 42 (24.6%) had 17p deletion. The median observation time was 40 months (range=1-59 months), while median ibrutinib monotherapy reached 37.5 months (range=0.4-59.2 months). Response was noted in 132 (77.2%) patients. The estimated 5-year progression-free survival (PFS) and overall survival (OS) rates were 61.1% (95%CI=49.3-70.9%) and 56.8% (95%CI=45.6-66.6%), respectively. At the time of analysis 97 (56.7%) remained under ibrutinib monotherapy. Conclusion Ibrutinib is clinically effective and tolerable as a monotherapy in real-world RR-CLL patients.

Purpose Daratumumab is a promising new agent for relapsed/refractory multiple myeloma (RRMM). However, there are limited data on its clinical activity and tolerability in the real-world patients. The purpose of this study is to determine the efficacy and toxicity profile of daratumumab monotherapy in the real-life setting. Patients and methods Thirty RRMM patients treated with daratumumab who had previously received at least three treatment lines including a proteasome inhibitor and an immunomodulatory drug or had been double refractory (DR MM) were included to the Polish Myeloma Group observational study. Results The objective response rate to daratumumab was 42.8%. Median progression-free survival (PFS) and overall survival reached 9.5 and 13.8 months, respectively. Importantly, patients with DR-MM had a significantly shorter PFS than other patients (median PFS of 4.1 vs. 12.1 months). Daratumumab was generally well tolerated, however two patients had their therapy interrupted due to adverse events. Conclusion Daratumumab monotherapy has significant activity and good tolerance in heavily pretreated RRMM patients.

Richter transformation (RT) of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) to Hodgkin lymphoma (HL) is a rare and unexpected event in the course of the disease and data on this phenomenon is still limited. To better understand the clinical and histological characteristics and the outcomes of HL variant of RT (HvRS) the Polish Lymphoma Research Group performed a nationwide survey which identified 22 patients with histologically proven HvRS diagnosed between 2002 and 2016. There were 16 (73%) males. The median age at CLL/SLL and HvRS diagnosis was 59 (39-77) and 64 (40-77) years, respectively. The median interval between CLL/SLL and HvRS diagnosis was 38 months (range: 0-187). All patients had an advanced stage HL, and majority, 17 (77%), presented with B symptoms. The predominant subtypes of HL were nodular sclerosis (12; 55%) and mixed cellularity (9; 41%). Eighteen patients received non-palliative treatment, including 13 who received driamycin, bleomycin, vinblastine, and dacarbazine (ABVD) regimen first line. Objective response was: 50%, with 33% complete remissions (61% and 46% for ABVD, respectively). Median overall survival reached 13.3 months (95% CI, 3.7-NA). The only adverse prognostic factor for survival was a higher number (≤1 versus ≥2) of prior lines of treatment given for CLL/SLL with HR 3.57 (95% CI, 1.16-10.92). We conclude, HvRS harbors a poor prognosis, especially in patients heavily pretreated for CLL/SLL. Response to standard first-line anti-HL chemotherapy is unsatisfactory, and new agents should be tested to improve the outcome.

PURPOSE Phosphatidylinositol-3-kinase (PI3K) inhibitors have shown activity in relapsed or refractory (R/R) indolent non-Hodgkin lymphoma (iNHL). PI3K inhibitors have been hampered by poor long-term tolerability and toxicity, which interfere with continuous use. Umbralisib, a dual inhibitor of PI3Kδ/casein kinase-1ε, exhibits improved selectivity for PI3Kδ compared with other PI3K inhibitors. This phase IIb trial was designed to evaluate the efficacy and safety of umbralisib in patients with R/R iNHL. PATIENTS AND METHODS In this multicohort, open-label, phase IIb study, 208 patients with R/R marginal zone, follicular, or small lymphocytic lymphoma (MZL, FL, or SLL) unresponsive to prior treatments (≥ 1 MZL; ≥ 2 FL/SLL), including ≥ 1 anti-CD20–based therapy, were administered umbralisib 800 mg orally once daily until disease progression, unacceptable toxicity, or study withdrawal. Primary end point is overall response rate; secondary end points include time to response, duration of response, progression-free survival, and safety. RESULTS The median follow-up is 27.7 months (efficacy) and 21.4 months (safety). The overall response rate was 47.1%, and tumor reduction occurred in 86.4% of patients. The median time to response was 2.7-4.6 months. The median duration of response was not reached for MZL, 11.1 months for FL, and 18.3 months for SLL. Median progression-free survival was not reached for MZL, 10.6 months for FL, and 20.9 months for SLL. At least one grade ≥ 3 treatment-emergent adverse event (TEAE) was reported in 53.4% of patients. TEAEs led to umbralisib discontinuation in 32 patients (15.4%). A total of 31 patients (14.9%) discontinued because of a treatment-related adverse event. Grade ≥ 3 TEAEs reported in ≥ 10% of patients: neutropenia (11.5%) and diarrhea (10.1%). Increased ALT/AST (grade ≥ 3) occurred in 6.7%/7.2% of patients. CONCLUSION Umbralisib achieved meaningful clinical activity in heavily pretreated patients with iNHL. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and adverse event–related discontinuations.

The optimal salvage therapy in relapsed/refractory Hodgkin lymphoma (R/R HL) has not been defined so far. The goal of this multicenter retrospective study was to evaluate efficacy and safety of BGD (bendamustine, gemcitabine, dexamethasone) as a second or subsequent line of therapy in classical R/R HL. We have evaluated 92 consecutive R/R HL patients treated with BGD. Median age was 34.5 (19–82) years. Fifty-eight patients (63%) had received 2 or more lines of chemotherapy, 32 patients (34.8%) radiotherapy, and 21 patients (22.8%) an autologous hematopoietic stem cell transplantation (autoHCT). Forty-four patients (47.8%) were resistant to first line of chemotherapy. BGD therapy consisted of bendamustine 90 mg/m2 on days 1 and 2, gemcitabine 800 mg/m2 on days 1 and 4, dexamethasone 40 mg on days 1–4. Median number of BGD cycles was 4 (2–7). The following adverse events ≥ 3 grade were noted: neutropenia (22.8%), thrombocytopenia (20.7%), anemia (15.2%), infections (10.9%), AST/ALT increase (2.2%), and skin rush (1.1%). After BGD therapy, 51 (55.4%) patients achieved complete remission, 23 (25%)—partial response, 7 (7.6%)—stable disease, and 11 (12%) patients experienced progression disease. AutoHCT was conducted in 42 (45.7%) patients after BGD therapy, and allogeneic HCT (alloHCT) in 16 (17.4%) patients. Median progression-free survival was 21 months. BGD is a highly effective, well-tolerated salvage regimen for patients with R/R HL, providing an excellent bridge to auto- or alloHCT.

Phosphoinositide 3-kinase-δ (PI3Kδ) inhibitors are active in lymphoid malignancies, although associated toxicities can limit their use. Umbralisib is a dual inhibitor of PI3Kδ and casein kinase-1ε (CK1ε). This study analyzed integrated comprehensive toxicity data from 4 open-label, phase 1 and 2 studies that included 371 adult patients (median age, 67 years) with relapsed/refractory non-Hodgkin lymphoma (follicular lymphoma [n = 147]; marginal zone lymphoma [n = 82]; diffuse large B-cell lymphoma/mantle cell lymphoma [n = 74]; chronic lymphocytic leukemia [n = 43]; and other tumor types [n = 25]) who were treated with the recommended phase 2 dose of umbralisib 800 mg or higher once daily. At data cutoff, median duration of umbralisib treatment was 5.9 months (range, 0.1-75.1 months), and 107 patients (28.8%) received umbralisib for ≥12 months. Any-grade treatment-emergent adverse events (AEs) occurred in 366 (98.7%) of 371 patients, with the most frequent being diarrhea (52.3%), nausea (41.5%), and fatigue (31.8%). Grade 3 or higher treatment-emergent AEs occurred in 189 (50.9%) of 371 patients and included neutropenia (11.3%), diarrhea (7.3%), and increased aminotransferase levels (5.7%). Treatment-emergent serious AEs occurred in 95 (25.6%) of 371 patients. AEs of special interest were limited and included pneumonia (29 of 371 [7.8%]), noninfectious colitis (9 of 371 [2.4%]), and pneumonitis (4 of 371 [1.1%]). AEs led to discontinuation of umbralisib in 51 patients (13.7%). Four patients (1.1%) died of AEs, none of which was deemed related to umbralisib. No cumulative toxicities were reported. The favorable long-term tolerability profile and low rates of immune-mediated toxicities support the potential use of umbralisib for the benefit of a broad population of patients with lymphoid malignancies.

Comorbidities impair the prognosis of diffuse large B-cell lymphoma (DLBCL). Type 2 diabetes mellitus (DMT2) increases the risk of other comorbidities, e.g., heart failure (HF). Thus, we hypothesized that pre-existing DMT2 may negatively affect the outcome of DLBCL. To verify this, DLBCL patients treated with (R)-CHOP were enrolled. 469 patients were eligible, with a median age of 57 years; 356 patients had advanced-stage DLBCL. 126 patients had high-intermediate and 83 high-risk international prognostic index (IPI). Seventy-six patients had DMT2, 46 HF; 26 patients suffered from both DMT2 and HF. In the analyzed group DMT2 or HF significantly shortened overall survival (OS) and progression free survival (PFS): the 5-year OS for patients with DMT2 was 64% vs 79% and for those with HF: 49% vs 79%. The 5-year PFS for DMT2 was 50.6% vs 62.5% and for HF 39.4% vs 63.2%. The relapse/progression incidence was comparable between groups; the non-relapse/progression mortality (NRPM) was significantly higher solely in DMT2 patients (5-year NRPM 22.5% vs 8.4%). The risk of death was higher in patients with higher IPI (HR = 1.85) and with DMT2 (HR = 1.87). To conclude, pre-existing DMT2, in addition to a higher IPI and HF, was a negative predictor for OS and PFS.

Summary R‐CVP (cyclophosphamide, vincristine, prednisone) and R‐CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone + rituximab) are immunochemotherapy regimens frequently used for remission induction of indolent non‐Hodgkin lymphomas (iNHLs). Rituximab maintenance (RM) significantly improves progression‐free survival (PFS) in patients with complete/partial remission (CR/PR). Here we report the final results of a randomized study comparing R‐CVP to R‐CHOP both followed by RM. Untreated patients in need of systemic therapy with symptomatic and progressive iNHLs including follicular (FL) and marginal zone lymphoma (MZL), mucosa‐associated lymphoid tissue (MALT), small lymphocytic (SLL), and lymphoplasmacytic (LPL) lymphoma were eligible. Patients were randomized to receive R‐CVP or R‐CHOP for eight cycles or until complete response (CR). All patients with CR/PR (partial response) received RM 375 mg/m2 q 2 months for 12 cycles. Primary endpoint was event‐free survival (EFS). Two‐hundred and fifty patients [FL 42%, MZL/MALT 38%, LPL/ Waldenström Macroglobulinaemia (WM) 11%, SLL 9%] were enrolled and randomized (R‐CHOP: 127, R‐CVP: 123). Median age was 56 years (21–85), 44% were male, 90% were in stage III–IV, 43% of FL patients had a Follicular Lymphoma International Prognostic Index (FLIPI) score ≥3, and 33·4% of all patients had an IPI score ≥3. At the end of induction treatment, the CR/PR rate was 43·6/50·9% and 36·3/60·8% in the R‐CHOP and R‐CVP groups (P = 0·218) respectively. After a median follow‐up of 67, 66, and 70 months, five‐year EFS was 61% vs. 56% (not significant), progression‐free survival (PFS) was 71% vs. 69% (not significant) and overall survival (OS) was 84% vs. 89% in the R‐CHOP vs. the R‐CVP arm respectively. Grade III/IV adverse events (65 vs. 22) occurred in 40 (33·1%) and 18 (15·3%) patients, P = 0·001; neutropenia in 16 (11·6%) and 4 (3·4%) patients, P = 0·017; infection in 14 (10·7%) and 3 (2·5%) patients,; P = 0·011; and a second neoplasm in three versus seven patients., in the R‐CHOP and the R‐CVP groups respectively. This multicentre randomized study with >five‐year follow‐up shows similar outcome in patients with indolent lymphoma in need of systemic therapy treated with R‐CVP or R‐CHOP immunochemotherapy and rituximab maintenance in both arms. The minor toxicity of the R‐CVP regimen makes it a reasonable choice for induction treatment, leaving other active agents like doxorubicin or bendamustin for second‐line therapy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is one of the aggressive rare hematopoietic malignancies with predilection to the skin, primarily found in adults. The precise incidence of BPDCN is difficult to estimate due to constantly changing nomenclature and lack of precise defining criteria prior to the 2008 WHO classification system. There are not many cases described in the literature, what makes the diagnostic process challenging. Skin lesions such as erythematous infiltrates and nodules are usually the first manifestation of the disease. Therefore, in doubtful diagnostic cases, dermatologists should perform histopathological and immunohistochemistry examinations along with hematological and oncological cooperation, as early diagnosis and appropriate treatment is essential for improvement of the disease course. This analysis, despite the small number of patients may provide useful information on the clinical and histopathological features of this rare malignancy.

Introduction: Patients with relapsed or refractory diffuse large B-cell lymphoma (RR DLBCL) who cannot tolerate or who are not eligible for autologous or chimeric antigen receptor T cell (CAR-T) therapy have limited therapeutic options and suboptimal long-term outcomes. In patients who were not eligible for HSCT, the rituximab plus gemcitabine, dexamethasone and cisplatin (R-GDP) regimen (and variations using methylprednisolone or carboplatin/oxaliplatin) have shown an overall response rates (ORR) of ~50%, a complete response (CR) rate of ~25% (Gopal, Leuk Lymphoma, 2010), and a median progression-free survival (PFS) and an overall survival (OS) of 3 and 9 months, respectively (Crump, Hematol Oncol Clin N Am. 2016; Gopal Leuk Lymphoma, 2010; Ng, Br J Cancer, 2005; Sirohi, Hematology, 2007; Barton, Eur J Haematol. 2015; Moccia Leuk Lymphoma, 2017). Selinexor is an oral small molecule selective inhibitor of exportin-1 (XPO1) mediated nuclear export (SINE) compound leading to activation of tumor suppressor proteins and reduction in oncoprotein levels. It also reduces the expression of deoxyribonucleic acid (DNA) damage repair proteins and therefore potentiates DNA damage-based therapies leading to an increased death of cancer cells. Selinexor has synergistic effects with gemcitabine and cisplatin, and enhanced anti-lymphoma effects with dexamethasone. In the SADAL study (n=134), single-agent oral selinexor 60 mg twice weekly induced an ORR of 29% and a CR rate of 13% in patients with RR DLBCL. The response rates were consistent across various subgroups including patients Selinexor in combination with R-GDP was evaluated in a Phase 1 clinical trial (SELINDA), in which patients with DLBCL received either 40 or 60 mg selinexor once or twice weekly in combination with standard dose R-GDP. The recommended phase 2 dose for further exploration was 40 or 60 mg once weekly with an ORR of 60-80%. Therefore, combining selinexor with R-GDP is expected to improve response rates, and continuation of treatment with single-agent selinexor is expected to prolong the duration of responses, improve PFS (and potentially OS) in patients with RR DLBCL. Materials and methods: XPORT-DLBCL-030 is a Phase 2/3, multicenter study. The Phase 2 portion of the study is an open-label randomized study to identify the optimal dose of selinexor (40 or 60 mg) in combination with R-GDP in patients (n=120) with RR DLBCL. Patients ≥18 years with 1-3 prior lines of therapy and ECOG performance status ≤2 who are not intended for HSCT or CAR-T therapy are randomized 1:1:1 to one of 3 treatment arms: Arm 1: selinexor 40 mg+R-GDP (S40+R-GDP); Arm 2: selinexor 60 mg+R-GDP (S60 + R-GDP); Arm 3: R-GDP. Combination treatment will be given for up to 6 cycles (21 days/cycle). After completing the SR-GDP combination therapy (EoC), patients in Arms 1 and 2 who reach at least partial response (PR), will receive weekly single-agent selinexor 60 mg (28 days/cycle) as "continuous therapy" until disease progression (PD) or unacceptable toxicity. After PD, patients will be followed up for survival. Patients in the R-GDP arm will be followed up for PD and survival. Patients who are ineligible for HSCT due to an active disease, or those who have primary refractory DLBCL, defined as no response or relapse within 6 months after ending first-line treatment, will be allowed to enroll in the study (up to 15% and 25%, respectively of all patients enrolled). The primary endpoint of the study is ORR according to the Lugano 2014 criteria. Secondary endpoints include PFS, OS, ORR-EoC, DOR and incidence and severity of adverse events. Figure 1 Figure 1. Disclosures Pinto: Takeda: Consultancy; MSD: Honoraria; Incyte: Honoraria; Roche: Honoraria, Speakers Bureau; Bristol Myers Squibb-CELGENE: Honoraria. Yimer: Texas Oncology: Current Employment; Pharmacyclics: Speakers Bureau; Amgen: Speakers Bureau; Sanofi: Speakers Bureau; GSK: Speakers Bureau; Beigene: Speakers Bureau; Janssen: Speakers Bureau; Astrazeneca: Speakers Bureau; Karyopharm: Current equity holder in publicly-traded company, Speakers Bureau. Manda: Morphosys: Honoraria; Genmab: Current equity holder in publicly-traded company. Canales: Sanofi: Consultancy; Incyte: Consultancy; Novartis: Consultancy, Honoraria; Sandoz: Honoraria, Speakers Bureau; iQone: Honoraria; Karyopharm: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; F. Hoffmann-La Roche Ltd: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Gilead/Kite: Consultancy, Honoraria; Eusa Pharma: Consultancy, Honoraria; Celgene/Bristol-Myers Squibb: Consultancy, Honoraria. Jurczak: European Medicines Agency, Sandoz-Novartis, Janssen China R&D, BeiGene, Epizyme, Acerta, AstraZeneca: Consultancy; AbbVie, AstraZeneca, Bayer, BeiGene, Celtrion, Celgene, Debbiopharm, Epizyme, Incyte, Janssen, Loxo Oncology, Merck, Mei Pharma, Morphosys, Novo Nordisk, Roche, Sandoz, Takeda, TG Therapeutics, Pharmacyclics, Affirmed, Gilead Sciences, Nordic Nanovecto: Research Funding; Jagiellonian University: Ended employment in the past 24 months; Maria Sklodowska-Curie National Research Institute of Oncology: Current Employment; AstraZeneca, BeiGene, Janssen, Loxo Oncology, Sandoz, Roche: Membership on an entity's Board of Directors or advisory committees. Sureda: Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; GSK: Consultancy, Honoraria, Speakers Bureau; Roche: Other: Support for attending meetings and/or travel; Bluebird: Membership on an entity's Board of Directors or advisory committees; Mundipharma: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Research Funding, Speakers Bureau; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel, Speakers Bureau. Ma: Karyopharm Therapeutics Inc.: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Li: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Ingalls: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Arriola: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Arazy: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Shah: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Shacham: Karyopharm: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: (8999996, 9079865, 9714226, PCT/US12/048319, and I574957) on hydrazide containing nuclear transport modulators and uses, and pending patents PCT/US12/048319, 499/2012, PI20102724, and 2012000928) . Kauffman: Karyopharm Therapeutics Inc.: Current Employment, Current equity holder in publicly-traded company. Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Background Umbralisib is an oral, once-daily inhibitor of PI3Kδ and CK1e that is highly selective for the delta isoform. The UNITY-NHL trial (NCT02793583) is a multicenter, open-label, Phase 2b study evaluating umbralisib in previously treated NHL patients. Herein, we present results from the UNITY-NHL study. Methods 208 patients with R/R marginal zone, follicular, or small lymphocytic lymphoma (MZL, FL, SLL) unresponsive to prior treatments (≥1 MZL; ≥2 FL/SLL), including ≥1 anti-CD20–based therapy, were administered umbralisib 800mg orally once-daily until disease progression, unacceptable toxicity, or study withdrawal. The primary endpoint of the study was overall response rate (ORR) as assessed by an independent review committee, according to the revised IWG criteria. Results At a median follow up of 27.8 months, MZL patients (n=69) had an ORR of 49.3% (95% CI 37.0% - 61.6%) with 15.9% achieving a complete response (CR), and a Disease Control Rate (DCR: CR+PR+SD) of 82.6%. Median time-to-response (TTR): 2.8 months (95% CI 2.7 - 2.9). No patient who achieved CR has progressed to date. At a median follow up of 27.5 months, FL patients (n=117) had an ORR of 45.3% (95% CI 36.1% - 54.8%) with 5.1% achieving a CR, and a DCR of 79.5%. Median TTR: 4.6 months (95% CI 3.0 - 5.6). At a median follow up of 29.3 months, SLL patients (n=22) had an ORR of 50.0% (95% CI 28.2 - 71.8) with 4.5% achieving a CR, and a DCR of 86.4%. Median TTR: 2.7 months (95% CI 2.4 - 2.8). At least one grade ≥3 treatment-emergent adverse event (TEAE) was reported in 53.4% of patients. TEAEs led to umbralisib discontinuation in 32 patients (15.4%). Grade ≥3 TEAEs reported in ≥10% of patients: neutropenia (11.5%) and diarrhea (10.1%). Increased ALT/AST (grade ≥3) occurred in 6.7%/7.2% of patients. Conclusions Umbralisib achieved meaningful clinical activity in a heavily pretreated iNHL population. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and AE-related discontinuations. These results suggest umbralisib has a favorable benefit-risk profile in this patient population and have supported the Accelerated Approval of umbralisib in previously treated MZL and FL patients.

Background The 17p deletion is regarded as the strongest poor prognostic factor in chronic lymphocytic leukemia (CLL). Results of recently performed clinical trials have suggested that ibrutinib significantly improves the outcome in this patient group. Aim The study aimed at analyzing the efficacy and adverse events profile of ibrutinib monotherapy in CLL patients with 17p deletion treated in routine clinical practice outside clinical trials. Materials and Methods Clinical response and adverse events profile of ibrutinib monotherapy were assessed in thirty-five CLL patients with 17p deletion treated within the ibrutinib named patients program in Poland. Results Overall response rate was 80% (28/35 patients) with median observation time of 24.2 months (range 0,1 – 30,9). Complete remission was observed in 5 patients (14.3%), partial remission in 11 (31.4%), partial remission with lymphocytosis in 13 (37.1%), whereas stable disease and progression was noted in 4 (11.4%) and 1 (2.9%) respectively. Response was not assessed in 1 patient. Median progression-free survival was 29.5 months, whereas median overall survival was not reached. Eleven patients died (7 because of infection, 1 of CLL progression, 1 of sudden cardiac death, 1 of disseminated breast cancer and 1 of unknown causes). In 13 patients (37.1%) at least one 3 or 4 grade adverse event occurred. In 11 patients (31.4%) the treatment was temporary withheld or the dose reduced due to adverse events. Conclusion Ibrutinib is characterized by high clinical efficacy and acceptable toxicity in CLL patients with 17p deletion in daily clinical practice.

Bendamustine and ibrutinib are commonly used in the treatment of patients suffering from chronic lymphocytic leukemia (CLL). In this study we compare efficacy and safety bendamustine versus ibrutinib therapy in previously untreated patients with CLL. Because there are no head-to-head comparisons between bendamustine and ibrutinib, we performed indirect comparison using Bucher method. A systematic literature review was performed and 2 studies published before June 2016 were taken into analysis. Treatment with ibrutinib significantly improves PFS determined by investigator (HR of 0.3; P = .01) and OS (HR of 0.21; P < .001. Our study indicates that ibrutinib therapy improves PFS, OS and is superior in terms of safety comparing with bendamustine therapy in CLL patients.

Background: Umbralisib is an oral, once-daily, dual inhibitor of phosphatidylinositol-3-kinase-delta (PI3Kδ) and casein kinase-1ε (CK1ε) that exhibits improved selectivity for the delta isoform of PI3K. The UNITY-NHL trial (NCT02793583) is a multicenter, open-label, registration directed Phase 2 study designed to evaluate the safety and efficacy of umbralisib in previously treated NHL patients (pts). Previously reported results in pts with relapsed/refractory (R/R) marginal zone lymphoma (MZL) demonstrated that umbralisib was active with a manageable safety profile. In contrast with other PI3K inhibitors, there was a low incidence of immune-mediated toxicities with umbralisib, possibly attributable to enhanced selectivity for the PI3Kδ isoform as well as inhibition of CK1ε. Herein, we present results from the final analysis of the iNHL population treated with single agent umbralisib. Methods: Eligible pts had histologically confirmed iNHL: MZL (splenic, nodal, extranodal), follicular lymphoma (FL; Gr 1, 2, 3a), or small lymphocytic lymphoma (SLL). MZL pts were R/R to ≥1 prior lines of treatment, which must have included an anti-CD20, while FL and SLL pts were R/R to ≥2 prior lines, which had to include an anti-CD20 and an alkylating agent. Umbralisib was administered orally at 800 mg once-daily in 28-day treatment cycles until disease progression or unacceptable tolerability. The primary endpoint of the study was overall response rate (ORR) as assessed by an independent review committee (IRC), according to the revised IWG criteria (Cheson 2007). Secondary endpoints included duration of response (DoR), progression-free survival (PFS), time to response (TTR), and safety. Pneumocystis jiroveci pneumonia (PCP) and anti-viral prophylaxis were mandated for all pts. Results: 208 iNHL pts received at least 1 dose of umbralisib, including 69 MZL, 117 FL, and 22 SLL pts. The median duration of exposure was 8.4 mos (range 0.2 - 27.0), median age was 66, and 56.7% were male. Pts had received a median of 2 prior regimens (range 1 - 10) with 46.1% having received ≥ 3 regimens. FL patients had a median of 3 prior regimens. With a median follow up of 27.8 mos, MZL pts had an ORR of 49.3% (95% CI 37.0% - 61.6%) with 15.9% achieving a complete response (CR), and a Disease Control Rate (DCR: CR+PR+SD) of 82.6%. ORR was consistent amongst MZL subtypes. The median TTR was 2.8 months (95% CI 2.7 - 2.9). The median profession-free survival (PFS) was not reached (95% CI 12.1 mos - not evaluable [NE]) with an estimated 12-month PFS rate of 64.2%. The median DoR was not reached (95% CI 10.3 mos - NE), and no pts who achieved CR have experienced disease progression to date. With a median follow up of 27.5 mos, FL pts had an ORR of 45.3% (95% CI 36.1% - 54.8%) with 5.1% achieving a CR, and a DCR of 79.5%. The median TTR was 4.6 mos (95% CI 3.0 - 5.6). The median PFS was 10.6 mos (95% CI 7.2 - 13.7) with an estimated 12-month PFS rate of 45.9%. The median DoR was 11.1 mos (95% CI 8.3 - 15.6). With a median follow up of 29.3 mos, SLL pts had an ORR of 50.0% (95% CI 28.2 - 71.8) with 4.5% achieving a CR, and a DCR of 86.4%. The median TTR was 2.7 mos (95% CI 2.4 - 2.8). The median PFS was 20.9 mos (95% CI 7.4 - 24.1) with an estimated 12-month PFS rate of 62.6%. The median DoR was 18.3 mos (95% CI 2.4 - NE). Best % change in target lesions form baseline for pts with at least one post-baseline assessment is shown in the figure. At the data cut-off, 60 pts (26 MZL, 27 FL, 7 SLL) remained on treatment. The most common ≥G3 AEs were neutropenia (11.5%), diarrhea (10.1%) and increased ALT/AST (7.2%). Other AEs of interest included pneumonitis (All G 1.4%; ≥G3 1.0%), and colitis (All G 1.4%; ≥G3 0.5%). Serious AEs were reported in 28.1% of pts, with 24.6% ≥G3. One patient with SLL had a fatal myocardial infarction (unrelated to umbralisib); there were no other G5 AEs. A total of 31 pts (14.9%) discontinued due a treatment-related adverse event (AE). Treatment-related AEs leading to dose reductions occurred in 20 (9.6%) pts. Conclusions: In the Phase 2 UNITY-NHL study, umbralisib achieved meaningful clinical activity in a heavily pretreated iNHL population. The safety profile was manageable, with a relatively low incidence of immune-mediated toxicities and AE-related discontinuations. These results suggest umbralisib has a favorable benefit-risk profile in this patient population and further development is ongoing. Figure Disclosures Zinzani: Kirin Kyowa: 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, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eusapharma: Consultancy, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Servier: Consultancy, Honoraria, 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; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jurczak:Sandoz-Novartis: Consultancy; Afimed: Research Funding; Acerta: Consultancy, Research Funding; Pharmacyclics: Research Funding; Bayer: Research Funding; Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland: Current Employment; TG Therapeutics, Inc.: Research Funding; Celgene: Research Funding; Servier: Research Funding; Takeda: Research Funding; Roche: Research Funding; Merck: Research Funding; MEI Pharma: Research Funding; Janssen China R&D: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy; European Medicines Agency,: Consultancy; Jagiellonian University, Krakow, Poland: Ended employment in the past 24 months; Epizyme: Consultancy; Gilead Sciences: Research Funding; MorphoSys: Research Funding; Nordic Nanovector: Research Funding. Ghosh:Kite/Gilead: Consultancy, Speakers Bureau; Juno/Celgene/Bristol-Myers Squibb: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; SGN: Consultancy, Research Funding, Speakers Bureau; TG Therapeutics: Consultancy, Research Funding; Roche/Genentech: Research Funding; Karyopharm: Consultancy; Genmab: Consultancy, Speakers Bureau; AbbVie: Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene/Bristol-Myers Squibb: Speakers Bureau; Forty Seven Inc: Consultancy, Other: Research Bureau, Research Funding; Janssen: Consultancy, Research Funding, Speakers Bureau. Derenzini:TG Therapeutics, Inc.: Research Funding. Cheah:Celgene, F. Hoffmann-La Roche, MSD, Janssen, Gilead, Ascentage Pharma, Acerta, Loxo Oncology, TG therapeutics: Honoraria; Celgene, F. Hoffmann-La Roche, Abbvie, MSD: Research Funding. Phillips:Karyopharm: Consultancy; Beigene: Consultancy; Seattle Genetics: Consultancy; BMS: Consultancy; Abbvie: Consultancy, Research Funding; AstraZeneca: Consultancy; Incyte: Consultancy, Other: travel expenses; Cardinal Health: Consultancy; Bayer: Consultancy, Research Funding; Pharmacyclics: Consultancy. Lech-Marańda:Roche, Amgen, Gilead: Speakers Bureau; Roche, Novartis, Takeda, Janssen-Cilag, Amgen, Gilead, AbbVie, Sanofi: Consultancy. Cheson:Abbvie: Consultancy, Research Funding; Kite: Consultancy; TG Therapeutics: Speakers Bureau; Morphosys: Consultancy; Symbio: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Research Funding; Jannsen: Consultancy; Parexel: Consultancy; Trillium: Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees. Caimi:Verastem: Other: Advisory Board; Celgene: Speakers Bureau; Amgen: Other: Advisory Board; Bayer: Other: Advisory Board; Kite Pharma: Other: Advisory Board; ADC Therapeutics: Other: Advisory Board, Research Funding. Leslie:BeiGene: Honoraria, Speakers Bureau; KitePharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Speakers Bureau; Celgene: Speakers Bureau; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; ADC therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Honoraria, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Chavez:Karyopharm: Consultancy; BeiGene: Speakers Bureau; Bayer: Consultancy; Merck: Research Funding; AbbVie: Consultancy; Genentech: Speakers Bureau; Epizyme: Speakers Bureau; Gilead: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy, Speakers Bureau; Celgene: Consultancy; Morphosys: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Verastem: Consultancy; Pfizer: Consultancy. Fonseca:Bristol-Myers Squibb Company: Speakers Bureau. Babu:Merck: Research Funding; Syndax: Research Funding; AbbVie: Research Funding; Janssen Oncology: Research Funding; TG Therapeutics: Research Funding; Amgen: Research Funding; Sanofi: Research Funding; Lutheran Hospital: Other; Argenx: Consultancy, Research Funding; Nektar: Research Funding; Novartis: Research Funding; Bayer: Honoraria; Lilly: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Alexion Pharmaceuticals: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Fort Wayne Medical Oncology & Hematology: Current Employment, Current equity holder in publicly-traded company; AstraZeneca/MedImmune: Research Funding; AstraZeneca: Consultancy, Honoraria; Genentech, Inc./ F. Hoffmann-La Roche: Research Funding; Boehringer Ingelheim: Consultancy. Hodson:Gilead Sciences: Research Funding. Burke:Bristol Myers Squibb: Consultancy; Verastem: Consultancy; Bayer: Consultancy; Astra Zeneca: Consultancy; Gilead: Consultancy; Seattle Genetics: Speakers Bureau; AbbVie: Consultancy; Morphosys: Consultancy; Adaptive: Consultancy; Epizyme: Consultancy; Kura: Consultancy; Celgene: Consultancy; Adaptive Biotechnologies: Consultancy; Roche: Consultancy. Sharman:TG Therapeutics: Consultancy, Research Funding; Bristol Meyers Squibb: Consultancy, Research Funding; BeiGene: Research Funding; Genentech: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Acerta: Consultancy, Research Funding; Roche: Consultancy, Research Funding; Celgene: Consultancy, Research Funding. O'Connor:Kymera Therapeutics: Current equity holder in private company, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Other: Data Safety Monitoring Committee, Research Funding; TG Therapeutics: Current Employment, Current equity holder in publicly-traded company; Servier: Consultancy; Mundipharma: Other: Consulting; Nomocan: Membership on an entity's Board of Directors or advisory committees; Merck: Research Funding; Astex Pharmaceuticals: Honoraria, Research Funding. Miskin:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Sportelli:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company. Weiss:TG Therapeutics, Inc.: Current Employment, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees. Fowler:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

We present the results of a prospective, non-randomized phase 2 trial in which 253 AML patients (pts) under 60 years old received DAC (Daunorubicin + AraC + Cladribine) as first induction followed by CLAM (Cladribine + AraC + Mitoxantrone) as early second induction on day 16 based on bone marrow (BM) blasts on day 14 (D14). The CR/CRi rate after a single course of DAC was 83% for pts with D14 BM blasts less than 10%. Forty-six pts had10% BM blasts on D14, of whom 35 received CLAM with rates of CR/CRi 60% and early death (ED) 23%. The remaining 11 pts were not fit to receive CLAM, with rates of CR/CRi 28%, PR 18%, and ED 18%. Median OS was 7.2 versus 7.5 months, respectively. The overall CR/CRi rate was 77% after the first induction, with final CR/CRi rate 80% after DAC reinduction for pts who achieved PR with initial DAC course. CLAM used as early second induction might improve CR/CRi rates for younger AML pts with poor early response to DAC induction, but may be associated with higher mortality.

We retrospectively analyzed long-term disease outcome of 350 elderly Hodgkin Lymphoma (eHL) patients treated with ABVD/ABVD-like regimen enrolled in the PLRG-R9 study between 2001 and 2013 in Poland. Complete remission was reported for 73% of early (ES) and 61% advanced stage (AS) patients. Nine (10%) ES and 56 (20%) AS patients have died. With the median follow-up of 36 (1-190) months, 3-year EFS and OS was 0.74 (95%CI: 0.63-0.85) and 0.90 (95%CI: 0.82-0.98) for ES; 0.51 (95%CI: 0.44-0.57), and 0.81 (95%CI: 0.75-0.86) for AS patients, respectively. For ES patients, Cox regression revealed ECOG2 and age70 as predictive for inferior OS and EFS. For AS patients, the most predictive for OS was the presence of cardiovascular disorders (CVD) (p = .00044), while for EFS four factors were significantly associated with a poor outcome: ECOG 2, age70 years, CVD and extranodal disease. In conclusion, CVD significantly impacts outcomes of ABVD-treated advanced eHL patients.

Background Myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML) patients, including those treated with azacitidine, are at increased risk for serious infections. The aim of our study was to identify patients with higher infectious risk at the beginning of azacitidine treatment. Patients and Methods We performed a retrospective evaluation of 298 MDS/CMML/AML patients and included in the analysis 232 patients who completed the first 3 cycles of azacitidine therapy or developed Grade III/IV infection before completing the third cycle. Results Overall, 143 patients (62%) experienced serious infection, and in 94 patients (41%) infection occurred within the first 3 cycles. The following variables were found to have the most significant effect on the infectious risk in multivariate analysis: red blood cell transfusion dependency (odds ratio [OR], 2.38; 97.5% confidence interval [CI], 1.21-4.79), neutropenia Conclusion We selected a subset with high early risk for serious infection and worse clinical outcome among patients treated with azacitidine.

Polish Lymphoma Research Group performed a phase-II trial to test whether (90)Y ibritumomab tiuxetan radioimmunotherapy (Y90) may constitute an alternative consolidation for mantle cell lymphoma patients unfit for high-dose therapy. Forty-six patients were consolidated with Y90 following response to the 1st (n = 34) or 2nd line (n = 12) (immuno)chemotherapy. Majority of the patients had advanced disease (stage IV and presence of B-symptoms in 85% and 70%, respectively) and high MIPI (5.8, range 4-7). Consolidation with Y90 increased the complete remission (CR) rate obtained by the 1st line therapy from 41% to 91% and allowed for median PFS of 3.3 and OS of 6.5 years. In the first relapse, CR rate increased from 16% to 75%, while median PFS and OS totaled 2.2 and 6.5 years, respectively. At 8 years, 30% of patients, consolidated in the 1st line CR were alive, without relapse. Toxicity associated with Y90 is manageable, more severe after fludarabine-based regimens.

A Correction to this paper has been published: 10.1007/s00277-021-04503-1

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK+ was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK+ treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK+ MK− and CK+ MK+ group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK− but not in MK+ group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK+.

We report a multicentre retrospective study that analysed clinical characteristics and outcomes in 117 patients with primary plasma cell leukaemia (pPCL) treated at the participating institutions between January 2006 and December 2016. The median age at the time of pPCL diagnosis was 61 years. Ninety-eight patients were treated with novel agents, with an overall response rate of 78%. Fifty-five patients (64%) patients underwent upfront autologous stem cell transplantation (ASCT). The median follow-up time was 50 months (95% confidence interval [CI] 33; 76), with a median overall survival (OS) for the entire group of 23 months (95% CI 15; 34). The median OS time in patients who underwent upfront ASCT was 35 months (95% CI 24·3; 46) as compared to 13 months (95% CI 6·3; 35·8) in patients who did not receive ASCT (P = 0·001). Multivariate analyses identified age ≥60 years, platelet count ≤100 × 109 /l and peripheral blood plasma cell count ≥20 × 109 /l as independent predictors of worse survival. The median OS in patients with 0, 1 or 2-3 of these risk factors was 46, 27 and 12 months, respectively (P < 0·001). Our findings support the use of novel agents and ASCT as frontline treatment in patients with pPCL. The constructed prognostic score should be independently validated.

Aim of the study To evaluate the efficacy and safety of Yttrium-90 Ibritumomab Tiuxetan ((90)Y-IT) as a consolidation therapy in the management of DLBCL. Material and methods Patients with primary refractory or high-risk DLBCL (n = 18), ineligible for autologous stem-cell transplantation, were included in a retrospective study performed at three centers by the Polish Lymphoma Research Group (PLRG). All patients (mean age 61, range 35-82) either didn't achieve a complete response or didn't complete the scheduled therapy due to its complications. Response rates (CR, PR, SD, PD) according to Cheson criteria, overall survival (OS), progression-free survival (PFS) and adverse effects of radioimmunotherapy were analyzed. Results Consolidation radioimmunotherapy increased the CR rate from 38% (n = 7) to 82% (n = 15). One patient remained in PR, one patient remained in SD, while one patient remained in PD. During a median follow-up of five years, 11 patients (62%) were alive with no recurrence, 4 patients (22%) were alive with relapse while 3 patients (16%) died. There was no statistically significant difference in PFS between those in CR and those in PR before (90)Y-IT. Conclusions Radioimmunotherapy is an effective consolidation therapy for high risk/refractory DLBCL patients and worthy of further investigation in prospective trials.

It is widely understood that outcomes of specific therapy and the burden of adverse events (AEs) found in clinical trials may differ from those seen in routine clinical practice. Several clinical t...

Background Interim PET after two ABVD cycles (iPET2) predicts treatment outcome in classical Hodgkin’s lymphoma. To test whether an earlier assessment of chemosensitivity would improve the prediction accuracy, we launched a prospective, multicenter observational study aimed at assessing the predictive value of iPET after one ABVD (iPET1) and the kinetics of response assessed by sequential PET scanning. Patients and methods Consecutive patients with newly diagnosed classical Hodgkin’s lymphoma underwent interim PET scan after one ABVD course (iPET1). PETs were interpreted according to the Deauville score (DS) as negative (−) (DS 1–3) and positive (+) (DS 4, 5). Patients with iPET1 DS 3–5 underwent iPET2. Results About 106 early (I–IIA) and 204 advanced (IIB–IV) patients were enrolled between January 2008 and October 2014. iPET1 was (−) in 87/106 (82%) or (+) in 19/106 (18%) of early, and (−) in 133/204 (65%) or (+) in 71/204 (35%) of advanced stage patients, respectively. Twenty-four patients were excluded from response analysis due to treatment escalation. After a median follow-up of 38.2 (3.2–90.2) months, 9/102 (9%) early and 43/184 (23%) advanced patients experienced a progression-free survival event. At 36 months, negative and positive predictive value for iPET1 were 94% and 41% (early) and 84% and 43% (advanced), respectively. The kinetics of PET response was assessed in 198 patients with both iPETs. All 116 patients with iPET1(−) remained iPET2(−) (fast responders), 41/82 with IPET1(+) became iPET2(−) (slow responders), and the remaining 41 stayed iPET2(+) (non-responders); progression-free survival at 36 months for fast, slow and non-responders was 0.88, 0.79 and 0.34, respectively. Conclusion The optimal tool to predict ABVD outcome in HL remains iPET2 because it distinguishes responders, whatever their time to response, from non-responders. However, iPET1 identified fast responders with the best outcome and might guide early treatment de-escalation in both early and advanced-stage HL.

Background Algorithm of anthracycline-based chemotherapy with favourable cardio-oncological outcome should be clearly re-defined for lymphoma patients with significant pre-existing cardiovascular diseases. A clinical benefit of liposomal forms of anthracycline is still debatable. Methods Polish registry included observations of 138 lymphoma patients with concomitant cardiovascular disorders who received liposomal doxorubicin as cardioprotective alternative of conventional form. It was created to analyse the importance of a strategy of administration of conventional/liposomal doxorubicin and a lifetime doxorubicin dose for development of acute decompensated heart failure (ADHF) as a reason of premature chemotherapy discontinuation. Results ADHF was the cause of premature termination of chemotherapy only in 11 patients (7.97%). The five new episodes of ADHF related to liposomal doxorubicin were recorded in subgroup of 70 patients with pre-existing heart failure (7.14%). There was the similar incidence of ADHF when liposomal doxorubicin was applied after conventional form in dose 200mg/m 2 or if earlier signs of iatrogenic myocardial damage was recognised: 5 cases in subgroup of 51 patients with baseline cardiovascular risk factors (9.8%). ADHF was observed in one of 17 patients (5.88%) receiving liposomal doxorubicin as second line chemotherapy after first line with conventional doxorubicin. Consequently throughout the study group ADHF didn't depend on the total cumulative dose of all types of doxorubicin: OR=0.85; 95%CI: 0.66–1.10; p=0.22 for each 50mg/m 2 . Conclusion The schedule of administration of conventional/liposomal doxorubicin can decide that lifetime combined doses of anthracyclines become insignificant for ADHF occurrence and premature discontinuation of chemotherapy in lymphoma patients with pre-existing cardiovascular disturbances.

We compared the outcomes of multiple myeloma (MM) patients aged 21–40 and 41–60 years in the novel agent era. This case-control study included 1089 patients between 2000 and 2015. Cases and controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 patients in the younger group and 916 patients in the older group. Younger patients presented with a higher incidence of lytic lesions (82% vs. 72%; P = 0·04) and high-risk cytogenetic abnormalities (83% vs. 68%; P = 0·007), but lower rate of elevated lactate dehydrogenase (21% vs. 44%; P

Background Brentuximab vedotin (BV) is an effective salvage treatment in patients with relapsing/progressive Hodgkin lymphoma (HL). However, it is unclear how much BV improved the outcome of BV naïve patients who relapsed after autologous hematopoietic stem cell transplantation (autoHCT) in real life. To address this question, we compared the outcome of patients who received conventional salvage treatment before the BV era to those who were treated with BV in haematological centres allied within the Polish Research Study Group. The goals of the study were to compare: the response rates to the conventional salvage chemotherapy and to the BV-based treatment, the proportion of patients proceeding to subsequent allogeneic (allo) or second autologous HCT and finally the overall survival (OS), and progression-free survival (PFS) of relapsing patients after autoHCT treated with and without BV. Methods and study group The study group consisted of adult patients with classical HL relapsing after first autoHCT who were treated either with conventional salvage chemotherapy (between 2001 and 2013; Group 1, n=121) or BV based treatment (between 2012 and 2018; Group 2, n=44). The groups did not differ in terms of age or gender. The patients in Group 2 received more chemotherapy lines before post-transplant salvage treatment (median 3, range 1-6) compared to those in historical Group 1 (median 2, range 1-6) (p=0.013). No patient was treated with immune check points inhibitors. The response to salvage treatment in the majority of patients in historical Group 1 was assessed with conventional computer tomography (CT), while in all patients in Group 2 with CT combined with positron emission tomography. Results The rate of the objective response rate defined as the complete or partial response was higher in Group 2 (84% vs 60%, p Conclusions In the era of brentuximab vedotin, significantly more patients with HL relapsing after autoHCT achieve objective response and proceed to allogeneic HCT. This most likely translates to the better PFS exceeding 24 months and most importantly to the significantly better OS of patients treated with BV compared to those treated with conventional salvage chemotherapy in the pre-BV era. Figure Disclosures Czyz: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dlugosz-Danecka:Roche: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Macrogenomics: Research Funding; Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Jurczak:Gilead: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Roche: Research Funding; Servier: Research Funding; MorphoSys: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Research Funding; Novo Nordisk: Research Funding; Bayer: Research Funding; Celtrion: Research Funding. Walewski:Gilead: Other: Travel Expenses; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Takeda: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees. Wrobel:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees. Zaucha:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees.

This report is a retrospective analysis of 65 patients with peripheral T cell lymphoma (PTCL), who underwent high-dose therapy and autologous hematopoietic stem cell transplantation (autoHCT) as a consolidation of first response achieved with either induction or salvage chemotherapy. We intended to determine the prognostic factors that influenced outcome after autoHCT and to define the predictive value of the scoring systems most often applied for transplant outcomes. Nineteen patients in either complete or partial remission underwent autoHCT after induction chemotherapy. Forty-six patients received second-line chemotherapy as a consolidation of partial response after induction chemotherapy (n = 34) or as a salvage therapy after primary induction failure (n = 12), and thereafter proceeded to autoHCT. Finally, the 36 patients were in complete remission, and 29 in partial remission at autoHCT. The median follow-up of survivors was 53 months (range 7–157 months). The 5-year overall survival and progression-free survival for all patients were 61.5 % (95 % CI 47.0–74.2 %) and 59.4 % (95 % CI 46.1–71.5 %), respectively. In multivariate analysis, bone marrow involvement at diagnosis and less than partial remission after induction chemotherapy were factors independently predictive for overall survival and progression-free survival. The prognostic index for PTCL could reliably stratify the prognosis of PTCL in this analysis.

A monosomal karyotype (MK) was identified by banding techniques (BT) in acute myeloid leukemia (AML). However, BT may be insufficient to determine the actual loss of a complete chromosome, especially in complex karyotypes. We have investigated the effect of monosomy type, total (MK-t) and partial (MK-p), reevaluated by FISH, on prognosis. We have found that complete remission rate and probability of overall survival at 1 year was higher in MK-p (n=27) than MK-t (n=15) group (40% vs. 15.4%, P=0.19 and 30% vs. 9%, P=0.046, respectively). Our results indicate for the first time that monosomy type influences the prognosis of MK-AML.

Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sezary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL.

This report is an analysis of patients with Hodgkin lymphoma who relapsed after autologous stem cell transplant (autoHCT) and who were treated with gemcitabine-based therapy as a bridge to either allogeneic or second autologous transplant. Sixteen patients were treated with gemcitabine, cisplatin and steroid and 21 with gemcitabine plus vinorelbine. The overall response rate was 68%. The grade 3-4 toxicity was myelosupression and infections. Fifteen patients proceeded to allogeneic and five to autologous transplant. Two-year overall survival (OS) and progression-free survival (PFS) for all patients were 36% and 25%, respectively. In multivariate analysis, relapse6 months after autoHCT and response to gemcitabine-based chemotherapy were associated with superior OS and response to gemcitabine-based chemotherapy with improved PFS. A treatment strategy based on gemcitabine-containing chemotherapy and second transplant appears to be an effective treatment option for patients relapsing6 months after autoHCT, providing a median survival time of 34 months.

An optimal treatment for patients with primary refractory or relapsed (R/R) Hodgkin lymphoma (HL) who did not respond to standard salvage therapy has not been established. Brentuximab vedotin (BV) and bendamustine (B) used as monotherapy were shown to be active in R/R HL and both are recommended as a therapeutic option. It has been proposed that the combination of BV with B (BVB) may improve the outcome of R/R HL patients. To test this hypothesis, we compared retrospectively the efficacy and safety of BV and BVB regimen in R/R HL patients. Methods: Since March 2014 all patients with R/R HL treated at PLRG centers were offered either BV in monotherapy every 21 days or in combination with B (B 90 mg/m² on days 1 and 2 of treatment cycle) according to the policy in each center. Results: BV or BVB therapy was administered to 94 patients (median age 33 years, range 18-68) with primary refractory (n=54) or relapsed HL (n=40), including 34 patients after autologous stem cell transplant (ASCT). The patients were treated with the median of 3 (range, 2-12) prior chemotherapy lines. Fifty-seven patients received BV and 37 patients BVB regimen. In 16 of them, BVB was de-escalated to BV after the median of 2 cycles (range, 2-7). The patients' and disease characteristics did not differ between two groups. In the whole study group, the median number of applied cycles per patient was 4 (range, 2-16). Dose-limiting toxicities were observed in 8% of patients. No difference was found between BV and BVB group, with similar rate of grade 3-4 neutropenia (16% vs 13%) and thrombocytopenia (4% vs 3%). Lung infection occurred in 1 patient treated with BV (2%) and 3 treated with BVB (2% vs 8%, p ns), with 2 treatment-related deaths in the BVB group. The response rate after 2 cycles of BV and BVB treatment defined as complete (CMR) or partial metabolic response (PMR) assessed by positron emission tomography was 69% (26% of CMR and 43% of PMR) and 89% (46% of CMR and 43% of PMR), respectively (p=0.036). After 4-6 cycles of treatment, CMR, PMR and stable metabolic disease was documented in 59%, 19% and 13% in the BV group vs. 71%, 17% and 3%, respectively, in the BVB group (p ns). Finally, 36 patients (22 from BV and 14 from BVB group) proceeded to ASCT, and 17 (9 from BV and 8 from BVB group) to allogeneic SCT. The overall and progression-free survival at 24 months were 80% and 51%. The survival curves did not differ between two study groups. In conclusion, our results suggest that BVB is a feasible regimen that provides higher response rate after 2 cycles compared to BV monotherapy. However, the overall response rate achieved after 4-6 cycles of treatment are comparable between BV monotherapy and combined BVB treatment. Infectious complications, including serious lung infections, were observed in both study groups, with two treatment-related deaths in the BVB group. Disclosures Dlugosz-Danecka: Roche: Consultancy; Servier: Consultancy. Jurczak:Nordic Nanovector: Research Funding; Epizyme: Research Funding; Beigene: Research Funding; Bayer: Research Funding; Celgene: Research Funding; Merck: Research Funding; Servier: Consultancy, Honoraria, Research Funding; European Medicines Agency: Consultancy; AstraZeneca: Consultancy; Gilead: Consultancy, Research Funding; Afimed: Research Funding; Morphosys: Research Funding; Janssen: Consultancy, Research Funding; Sandoz-Novartis: Consultancy; Roche: Research Funding; Pharmacyclics: Research Funding; Acerta: Consultancy, Research Funding; TG therapeutics: Research Funding. Zaucha:Roche: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Celgene: Honoraria.

WPROWADZENIE Immunochemioterapia R‑CHOP (rytuksymab, cyklofosfamid, doksorubicyna, winkrystyna, prednizon) jest standardem leczenia pierwszego rzutu w przypadku chłoniaka rozlanego z dużych komórek B (diffuse large B‑cell lymphoma – DLBCL). Żadne z badań randomizowanych nie udowodniło istotnej statystycznie korzyści w zakresie całkowitego przeżycia (overall survival – OS) w podgrupie dużego ryzyka wg Międzynarodowego Wskaźnika Prognostycznego (International Prognostic Index, IPI). CELE Zbadaliśmy retrospektywnie rolę dodania rytuksymabu do chemioterapii opartej na antracyklinie u chorych z DLBCL dużego ryzyka wg IPI. PACJENCI I METODY 371 chorych z DLBCL dużego ryzyka leczonych w 15 polskich ośrodkach hematologicznych poddano retrospektywnie analizie w dwóch odrębnych grupach wiekowych: >60 i ≤60 rż. Porównywano i analizowano odsetki odpowiedzi na leczenie, OS i przeżycie wolne od progresji (progression‑free survival – PFS). WYNIKI Całkowity odsetek odpowiedzi (overall response rate – ORR) u chorych z DLBCL dużego ryzyka istotnie zwiększył się u chorych leczonych rytuksymabem w porównaniu z chorymi leczonymi bez rytuksymabu (76,7% vs 95,6%; p

Our previously published study showed promising results of autologous stem cell transplantation (ASCT) in patients with primary resistant Hodgkin's disease (HD). Probabilities of overall survival (OS) and progression-free survival (PFS) at 3 years were 55 and 36%, respectively. The present study was undertaken to compare these results with conventionally treated patients and thus evaluate therapeutic options. Retrospective data on 76 adult patients who underwent ASCT were matched with 76 conventionally treated patients from 17 centers. Comparison of clinical characteristics in both groups showed that ASCT patients were younger (24 vs 31.5 years, P=0.001), more frequently presented with 'B' symptoms (P=0.03) and that more patients treated with chemotherapy (CT) had elevated LDH (P=0.03). In univariate analyses, bulky disease (P=0.0043) and complete resistance to standard CT (P=0.051) were found to be risk factors for OS. In a multivariate survival analysis only bulky disease was found to an independent prognostic factor (P=0.005). There was no difference in survival between the treatment groups with 5 years OS 33.7 (CI: 23-46) in the ASCT group and 35.6% (CI: 25-50) for the CT group (P=0.92). We conclude that ASCT is not superior to standard CT for treatment of patients with primary refractory HD.

ObjectiveIn order to evaluate the biocompatibility profile of a newly designed peritoneal dialysis fluid (PDF), we evaluated peritoneal leukocyte (PMΦ) cytokine release following overnight in vivo dwells using standard, lactate-buffered, single-chamber bag PDF (Lac-PDF) and purely bicarbonate-buffered, double-chamber bag PDF containing 34 (Bic-PDF) or 39 (Bic Hi-PDF) mmol/L bicarbonate.DesignA randomized, open, crossover clinical trial with single weekly test dwells was performed in stable, long-term continuous ambulatory PD patients ( n = 8). During 8-hour overnight dwells, PMΦ were exposed to different PDF containing 1.5% glucose. After drainage, peritoneal cells were isolated and incubated with RPMI 1640 medium for 2 or 3 hours, with and without stimulation by lipopolysaccharide (LPS). Ex vivo release of tumor necrosis factor (TNF)-α and interleukin (IL)-6 was measured by specific ELISA technique.ResultsAfter pre-exposure to Lac-PDF, PMΦ generated 242 ± 279 pg TNFα/106cells and 157 ± 105 pg IL-6/106cells. When pre-exposed to Bic-PDF and Bic Hi-PDF, TNFα and IL-6 production of PMΦ was not significantly different from Lac-PDF. After LPS stimulation (100 ng/mL), PMΦ secretion of TNFα and IL-6 pre-exposed to three PDF revealed no significant differences between groups: TNFα was 2864 ± 1216, 2910 ± 1202, and 3291 ± 558 pg/106cells after overnight dwells with Lac-PDF, Bic-PDF, and Bic Hi-PDF, respectively. Comparably, LPS-stimulated (100 pg/mL) PMΦ showed IL-6 secretion of 891 ± 335, 1380 ± 1149, and 1442 ± 966 pg/106cells for Lac-PDF, Bic-PDF, and Bic Hi-PDF.ConclusionAfter long-term overnight dwells, initial pH, the different buffers, and varying glucose degradation product levels of PDF do not strongly affect PMΦ function with respect to cytokine release. The lack of significant differences between fluids may result from the complete dialysate equilibration achieved during the overnight intraperitoneal dwell.

TPS7068 Background: Gilteritinib, a highly selective, potent FLT3/AXL inhibitor, showed antileukemic activity with favorable tolerability in a Phase 1/2 trial of FLT3 mutation-positive (FLT3mut+) relapsed/refractory AML. In FLT3mut+ AML cell lines, gilteritinib plus azacitidine (AZA) inhibited growth, and induced apoptosis and differentiation. This ongoing Phase 2/3 trial will examine the efficacy, safety, and tolerability of gilteritinib alone, gilteritinib plus AZA or AZA alone in newly diagnosed FLT3mut+AML patients ineligible for intensive induction chemotherapy. Methods: This open-label, 3-arm, 2-stage randomized trial (NCT02752035) will enroll ~540 newly diagnosed adults with FLT3mut+ (FLT3-ITD or -TKD) AML; those with APL, BCR-ABL+, or active CNS leukemia will be excluded. Before initiation, the safety and tolerability of gilteritinib plus AZA will be assessed in a Safety Cohort to establish the appropriate gilteritinib dose for combination therapy. Subjects will then be randomized 1:1:1 to receive oral gilteritinib alone (120 mg daily; Days 1–28), AZA alone (75 mg/m2 by subcutaneous injection or intravenous infusion on Days 1–7), or AZA (75 mg/m2; Days 1–7) plus oral gilteritinib (daily on Days 1–28 at the dose determined from the Safety Cohort), and stratified by age ( < 75 vs ≥75 years). Subjects will continue treatment until a discontinuation event occurs. The primary endpoint is overall survival of subjects receiving gilteritinib or gilteritinib plus AZA versus AZA alone; the key secondary endpoint is event-free survival. Additional secondary endpoints: complete remission rate, leukemia-free survival, remission duration, composite remission rate, tolerability, and fatigue. Dose changes and interruptions are allowed in all treatment arms. A formal interim futility analysis by an Independent Data Monitoring Committee is planned when ~50 subjects in each treatment arm have either discontinued therapy or completed 2 treatment cycles. Enrollment began on November 21, 2016; as of January 31, 2017, the Safety Cohort is ongoing. Clinical trial information: NCT02752035.

Background Although controlled-rate freezing and storage in liquid nitrogen are the standard procedure for peripheral blood progenitor cell (PBPC) cryopreservation, uncontrolled-rate freezing and storage at -80 degrees C have been reported. Study design and methods The prospective evaluation of 109 autologous PBPC transplantations after uncontrolled-rate freezing and storage at -80 degrees C of apheresis products is reported. The cryoprotectant solution contained final concentrations of 1-percent human serum albumin, 2.5-percent hydroxyethyl starch, and 3.5-percent DMSO. Results With in vitro assays, the median recoveries of nucleated cells (NCs), CD34+ cells, CFU-GM, and BFU-E were 60.8 percent (range, 11.2-107.1%), 79.6 percent (6.3-158.1%), 35.6 percent (0.3-149.5%), and 32.6 percent (1.7-151.1%), respectively. The median length of storage was 7 weeks (range, 1-98). The median cell dose, per kg of body weight, given to patients after the preparative regimen was 6.34 x 10(8) NCs (range, 0.02-38.3), 3.77 x 10(6) CD34+ cells (0.23-58.5), and 66.04 x 10(4) CFU-GM (1.38-405.7). The median time to reach 0.5 x 10(9) granulocytes per L, 20 x 10(9) platelets per L, and 50 x 10(9) reticulocytes per L was 11 (range, 0-37), 11 (0-129), and 17 (0-200) days, respectively. Hematopoietic reconstitution did not differ in patients undergoing myeloablative or nonmyeloablative conditioning regimens before transplantation. Conclusion This simple and less expensive cryopreservation procedure can produce successful engraftment, comparable to that obtained with the standard storage procedure.

Premature cardiovascular mortality related to chemotherapy and occurred in lymphoma survivors before disease progression is one of significant clinical failure of modern hematology. The aim of this retrospective analysis was to evaluate early cardiovascular mortality and its predictors in patients treated with the (R)-CHOP regimen.The study assessed 610 patients: 581 patients were treated with non-liposomal doxorubicin (cumulative dose of 337 ± 96 mg/m2), and 29 patients with liposomal non-pegylated doxorubicin (cumulative dose of 237 ± 126 mg/m2). Their present status, history of cardiovascular diseases and associated risk factors were recorded.The analysis identified 93 deaths (15.5%): 51 cases (55%) related to lymphoma disease progression and 28 (30%) to cardiovascular complications. Multivariate Cox analysis revealed history of previous heart diseases (HR=4.71; CI: 3.82-5.6; p0.001), ECG rhythm abnormalities related to chemotherapy (HR=4,78; CI: 3.63-5.92; p=0,01), and lack of complete remission (HR=2.73; CI: 1.78-3.66; p=0.03), as the independent predictors for cardiovascular death. Neither decreased LVEF nor increasing cumulative dose of anthracyclines had a significant predictive value for cardiovascular prognosis.The study indicated that cardiovascular mortality in lymphoma patients treated with (R)-CHOP regimen is relatively high and ECG monitoring may be the most effective in cardiological risk assessment. The unfavorable outcome depended on lack of complete remission that seems to be a consequence of patients' individual susceptibility for cardiac events, which should become a purpose of further trials.

Background: Several studies confirmed the predictive role on treatment outcome of interim-PET after 2nd ABVD cycle (iPET2) in Hodgkin lymphoma (HL). We hypothesized that interim PET after 1st cycle (iPET1) might define chemosensitivity with a better accuracy than iPET-2. To test this hypothesis, PLRG launched in 2008 a prospective multicenter observational study aiming at assessing the prognostic role of iPET1 and the dynamic of sequential PET response to ABVD. Methods: Adult pts with newly diagnosed early (stage I-IIA) and advanced (stage IIB-IV) consecutively enrolled in 11 Polish centers were risk-stratified by the EORTC/GELA criteria and treated according to the ESMO guidelines: ABVD x 3-4 cycles + IFRT in early stage, ABVD x 6 ± consolidation RT in advanced stage disease. Patients were scanned with iPET1 and iPET2 and no treatment change was permitted based solely on iPET results, with the exception of clinical or radiological evidence of overt HL progression. After the first interim analysis (52 pts enrolled, 2010), which demonstrated that all the iPET1 negative patients had also a negative iPET2, the protocol was amended, limiting the iPET2 scans only to pts with iPET1 Deauville score 5,4,3. Quality control for PET-CT was supervised by the Italian-Polish core lab using a standard methodology. PET scans were interpreted locally according to the Deauville 5-point scale: Score 1 to 3, was considered a negative (-), score 4 to 5 a positive (+) scan. Subsequently all PET scans were uploaded to the web platform WIDEN® for central review and Italian-Polish expert panel (EP) scored them afresh. Discorcondant cases were discussed in a joint review session with all the five EP members. Binary and overall concordance rates were calculated using k Cohen's and alpha Krippendorf's coefficients, respectively. Negative (NPV) and positive predictive values (PPV) of iPET1 were calculated using time to progression free survival (PFS) event. Results: Between 2008 and 2014, 346 pts were registered. 35 pts were excluded from the analysis for absence/poor quality of images resulting in 108(35%) assessable pts with early and 203(65%) with advanced HL. Median age at diagnosis was 31(18-80) years. iPET1 was scored 1-3 in 87/108(81%), and 4-5 in 21/108(19%) of pts with early and in 133/203(65%), and 70/203(35%) with advanced stage, respectively. Out of 91pts with positive iPET1, 83 pts underwent iPET2, which remained (+) in 41/83(49,4%) pts. In 22 pts treatment was escalated. 11 of those pts, in whom the treatment escalation was decided solely on positive iPET were excluded from the analysis; the remaining had symptoms or CT evidence of progression. After a median follow-up of 40,2 (3,2-90,2) months 300 pts (103 "early" and 197 "advanced") were evaluable. 65(21,7%) of them (9 in early and 56 in advanced group) had a PFS event: in "early" group 9(9%) showed disease progression (4 with iPET1(-) and 5 with IPET1(+)) and 1 of them died. In advanced stage 49(25%) pts showed disease progression (16 with iPET1(-) and 33 withiPET1(+)) out of whom 13 died; 7 additional pts died without HL progression: 4 from toxicity and 3 from unrelated events. At 36 months NPV and PPV of iPET1 was 93% and 45% in "early" and 81% and 52% in "advanced" group, respectively. The dynamic of response to ABVD was assessed in 189 pts who underwent both iPETs. All 116 pts with iPET1(-) remained (-) in iPET2-(fast-responders). Out of 83pts with IPET1(+) 39 (47%) became iPET2(-)-(slow responders); the rest (34pts: 41%) remained iPET2(+)-(no responders). PFS for fast-responders @36 months was 85%, for slow-responders 80% (log rank p=0,36) and for no-responders 25% (log rank p=0,0000). The EP changed the local iPET1 score in 27 cases: in 14 from (+) to (-) in 13 from (-) to (+). The inter-observer-agreement among reviewers on evaluating a positive vs. negative interim PET scans was good, Fleiss' kappa = 0.73, comparable to that found in analogous studies (IVS, HD0607). Conclusion: iPET1 fails to better identify chemosensitivity in ABVD-treated HL compared to iPET2. PPV of iPET1 is substantially inferior to the published results for iPET2. However NPV of iPET1 is comparable to iPET2 and therefore might guide early treatment de-escalation strategies. Disclosures Zaucha: Roche: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau; Takeda: Honoraria, Speakers Bureau. Knopinska-Posluszny:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Speakers Bureau; Teva: Other: travel, accommodation, Speakers Bureau. Walewski:Mundipharma; Roche; Takeda: Honoraria, Other: Travel expenses; Amgen; Boehringer Ingelheim; Celgene; Janssen-Cilag; Mundipharma; Roche; Takeda; Teva: Consultancy; Bayer (Inst); Bayer/Onyx (Inst); Boehringer Ingelheim (Inst); Celgene (Inst); Celltrion (Inst); Gilead Sciences (Inst); GlaxoSmithKline (Inst); GlaxoSmithKline (Inst); Mundipharma (Inst); Pfizer (Inst); Roche (Inst); Roche/Genentech (Inst); Seattle Geneti: Research Funding.

Introduction: Central nervous system involvement (CNSi) in acute myeloid leukemia (AML) can be found both at the time of diagnosis and during the AML course, with an incidence of 5-15%. However, there is lack of precise clinical characteristics and commonly recommended therapies for AML patients with the CNSi. Such patients demonstrate worse prognosis and reduced survival compared to those without CNSi, therefore allocation them to the allogeneic hematopoietic stem cell transplantation (allo-HSCT) regardless of their cytogenetic risk seems to be the best treatment option. Aims: The aim of the study was to assessed clinical characteristics and treatment outcome of patients with AML and the CNSi who were treated between 2004 and 2014 in 8 hematology departments of the Polish Adult Leukemia Group (PALG). Results: The analysis comprised 65 patients (62% males and 38% females) with the median age of 45 years (range 20-81 years). The CNSi was observed in 33 (51%) patients at the time of AML diagnosis (group 1) and in 32 (49%) subjects during the course of AML (group 2). The most common neurological symptoms were headaches (47% vs 48%, p= 0.99) and altered mental status (21% vs 30%, p= 0.32) observed in the group 1 and 2, respectively. Higher rates of paraparesis (39% vs 9%, p= 0.002) and motor deficits (33% vs 9%, p= 0.011) were noted in the group 2 compared to the group 1. The CNSi was the most frequently found in the AML not otherwise specified (AML NOS) subtype (61% in the group 1 and 50% in the group 2; p= 0.39). The AML subtype with recurrent cytogenetic abnormalities was diagnosed in 30% of patients form the group 1 and 28% of subjects from the group 2 (p= 0.85). The therapy and dysplasia related AML subtype was diagnosed in 6% of patients from the group 1 compared to the 16% of patients from the group 2 (p= 0.21). Using the FAB classification of AML, the CNSi in the group 1 occurred more often among patients with the M4 (42%) and the M5 (30%) subtype, whilst in the group 2 it was found in the M2 (25%) and the M5 (22%) subtype. The cytogenetic risk distribution according to the SWOG (ie. favorable, intermediate and poor) were 13%, 28% and 16% in the group 1 and 18%, 15% and 21 % in the group 2, respectively (p=0,39). The group 1 was more likely to have abnormal cytogenetics involving the chromosome 8 or 16 compared to the group 2 (62% vs 27%, p= 0.012). After the diagnosis of the CNSi, systemic chemotherapy was administered to 100% of patients from the group 1 and to 80% of patients from the group 2. Intrathecal chemotherapy was administered to 94% patients in both groups, whereas 19% of patients were subjected to subsequent brain radiation therapy. The cytarabine with methotrexate with corticosteroid was given intrathecally to 83% of patients, whilst the cytarabine monotherapy, the methotrexate with or without corticosteroid and liposomal cytarabine were given intrathecally to 1.5%, 9.1% and 18.2% patients, respectively. The CNS remission rate was higher in the group 1 compared to the group 2 (72% vs 39%, p= 0,003). Allo-HSCT in the first complete remission (CR1) as well as allo-HSCT after the AML relapse were performed with similar frequency in the both groups (21% vs 25%; p= 0.72 and 12% vs. 16%; p=0.73, respectively). The probability of a 1-year overall survival (OS) between the group 1 and 2 was not significantly different (52% vs 58% , p= 0.8). However, the OS rate was significantly higher in patients who underwent allo-HSCT in their CR1 compared to that in the patients without allo-HSCT (94% vs 39%; p Conclusions: The cytogenetic profile seems to be a key difference in patients' characteristics with the CNSi at the time of diagnosis or during the course of AML, with the chromosome 8 or 16 aberrations observed more often in the former group. The survival of AML patients with CNSi was short with the 1-year OS rate below 60%. However, the OS rate was significantly improved in those patients who underwent allo-HSCT in their CR1. Disclosures No relevant conflicts of interest to declare.

Elderly patients with Hodgkin lymphoma (HL) have poor prognosis. The inferior outcome has been attributed to a variety of factors including histologic differences, higher incidence of advanced stages, presence of comorbidities, poor performance status, inability to tolerate chemotherapy at full dose and increased treatment-related toxicity and mortality. ABVD is recommended and widely used for elderly patients (pts) although no prospective studies exist to justify this guideline. Moreover there are only few studies, yet most limited in numbers of pts, evaluating the results of HL treatment in elderly population. Here we present the retrospective analysis of outcome of 414 elderly HL pts treated by PLRG allied centers between 2003-2013. Group consisted of 237 men and 177 women. Their median age was 60,5 (50-93) years with the following age ranges:50-59 years-50%, 60-69 years-27%, ≥ 70 years-23%. Histology subtype showed predominance of nodular sclerosis 56%, followed by mixed cellularity 30%. 168 (41%) pts presented with early stage (I,II Ann Arbor) and 246 (59%) with advanced stage (III, IV Ann Arbor). 384 patients were treated with ABVD or ABVD-like regimen, few with CHOP-like(14), BEACOPP(9), PVAG (5) or with corticosteroids only(2). The median follow-up was 28,7 months. The response rates according to age groups are shown in Table 1. Progression free survival (PFS) and overall survival (OS) for all pts were 21 months and 39,5 months, respectively. Median PFS in group 50-59yrs and group 60-69yrs was similar 21,3 months and 22months respectively but was statistically significantly longer than in pts≥70 years old (16 months) (p Comorbidities were evidently more common in older patients: 30% in 50-59 yrs old, 65% in 60-69 yrs old, 85% in ≥70 yrs old. However, irrespective of age, patients with high burden of cardiovascular disease showed significantly poorer OS and PFS than those with comorbidities other than cardiovascular (OS 29 months vs 41 months, PFS 9 months vs 21 months, respectively, p Univariate analysis with Cox regression model including age ≥60, clinical stage >II, presence of B symptoms, IPS>2, serum albumin level below normal, ECOG>1, male sex, erythrocyte sedimentation rate ESR>10 and white blood cells count above the upper limit showed that age ≥60 (p=0.02), clinical stage >II (p=0.04), B symptoms (p=0.01), IPS>2 (p=0.02) and low serum albumin level (p=0.001) had statistically significant negative impact on OS. Multivariate analysis confirmed the significantly negative impact on OS of age ≥60 (p=0.005), IPS>2 (p=0.004) and low albumin level (p=0.002). Although, in our cohort overall response rate was better than in other studies, the outcome is still worse than in younger patients with HL. Specifically the prognosis of patients older than 60 years is even worse than patients who are 10 years younger. Our data also show that ABVD is not appropriate for very elderly patients (≥ 70 years old) and also for those with cardiovascular comorbidities irrespective of age. To find successful strategy for older and frail patients novel approaches should be tested in future trials. Table 1. Response rate according to age. Age, range 50-59 years old 60-69 years old ≥ 70 years old Ann Arbor stage n I-II 89 III-IV 123 I-II 43 III-IV 69 I-II 36 III-IV 54 CR* 79,8% 61,8% 69,8% 60,9% 52,8% 55,6% PR 18,0% 19,5% 23,3% 21,7% 38,9% 27,8% PD 0,0% 4,9% 0,0% 7,2% 0,0% 9,3% 3NR 2,2% 13,8% 7,0% 10,1% 8,3% 7,4% *CR- complete remission, PR- partial remission, PD- progressive disease, NR- no response. Disclosures No relevant conflicts of interest to declare.