Search

The Lugano classification for response assessment in lymphoma recommends the use of the 5-point-scale Deauville Score (DS) to assess response evaluation of end-of-treatment FDG-PET/CT (eotPET) in Hodgkin Lymphoma (HL); nevertheless, there is a paucity of data on its accuracy and reproducibility. We focus here on the cohort of advanced stage IIb-IV HL patients enrolled in the HD0607 clinical trial (NCT identifier 00795613) that having had a negative interim PET performed 6 cycles of ABVD (Doxorubicin, Vinblastine, Vincristine and Dacarbazine) and then performed an eotPET. Negative patients were randomized to radiotherapy and no further treatment while positive patients were treated based on local policies. eotPET was re-evaluated independently by two readers evaluated and progression free survival was analysed (PFS). eotPET of 254 patients were analysed. The median follow-up was 43 months. The best receiver operator characteristics cut-off values to distinguish positive and negative patients was 4. The area-under-the-curve was 0.81 (95%CI, 0.70-0.91). Three-years PFS was 0.95 (95% CI 0.90-0.97) in eotPET negative and 0.22 (95% CI 0.11-0.43) in eotPET positive. DS demonstrated a good reproducibility of positivity/negativity between the readers consensus and local site evaluation where the agreement occurred on 95.0% of patients. The present study demonstrates that eotPET is an accurate tool to predict treatment outcome in HL and confirms the appropriateness of the Lugano classification for eotPET evaluation.

PURPOSE To investigate the role of consolidation radiotherapy (cRT) in advanced-stage Hodgkin lymphoma (HL) presenting at baseline with a large nodal mass (LNM) in complete metabolic response after doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy. PATIENTS AND METHODS Advanced-stage (IIB-IVB) HL patients, enrolled in the HD 0607 trial (Clinicaltrial.gov identifier NCT00795613 ), with both a negative PET after two (PET-2) and six (PET-6) ABVD cycles, who presented at baseline with an LNM, defined as a nodal mass with the largest diameter ≥ 5 cm, were prospectively randomly assigned to receive cRT over the LNM or no further treatment (NFT). RESULTS Among 296 randomly assigned patients, the largest diameter of LNM at baseline was 5-7 cm in 101 (34%; subgroup A) and 8-10 cm in 96 (32%; subgroup B), whereas classic bulky (diameter > 10 cm) was detected in 99 (33%; subgroup C). Two hundred eighty patients (88%) showed a postchemotherapy RM. The median dose of cRT was 30.6 Gy (range, 24-36 Gy). After a median follow-up of 5.9 years (range, 0.5-10 years), the 6-year progression-free survival rate of patients who underwent cRT or NFT was, respectively, 91% (95% CI, 84% to 99%) and 95% (95% CI, 89% to 100%; P = .62) in subgroup A; 98% (95% CI, 93% to 100%) and 90% (95% CI, 80% to 100%; P = .24) in subgroup B; 89% (95% CI, 81% to 98%) and 86% (95% CI, 77% to 96%; P = .53) in subgroup C (classic bulky). CONCLUSION cRT could be safely omitted in patients with HL presenting with an LNM and a negative PET-2 and PET-6 scan, irrespective from the LNM size detected at baseline.

Purpose To investigate the progression-free survival (PFS) of patients with advanced Hodgkin lymphoma (HL) after a risk-adapted treatment strategy that was based on a positive positron emission tomography scan performed after two doxorubicin, vinblastine, vincristine, and dacarbazine (ABVD) cycles (PET2). Patients and Methods Patients with advanced-stage (IIB to IVB) HL were consecutively enrolled. After two ABVD cycles, PET2 was performed and centrally reviewed according to the Deauville five-point scale. Patients with a positive PET2 were randomly assigned to four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) followed by four cycles of standard BEACOPP with or without rituximab. Patients with a negative PET2 continued ABVD, and those with a large nodal mass at diagnosis (≥ 5 cm) in complete remission with a negative PET at the end of chemotherapy were randomly assigned to radiotherapy or no further treatment. The primary end point was 3-year PFS. Results Of 782 enrolled patients, 150 (19%) had a positive and 630 (81%) a negative PET2. The 3-year PFS of all patients was 82%. The 3-year PFS of those with a positive and negative PET2 was 60% and 87%, respectively ( P < .001). The 3-year PFS of patients with a positive PET2 assigned to BEACOPP with or without rituximab was 63% versus 57% ( P = .53). In 296 patients with both interim and post-ABVD–negative PET who had a large nodal mass at diagnosis, radiotherapy was randomly added after chemotherapy without a significant PFS improvement (97% v 93%, respectively; P = .29). The 3-year overall survival of all 782 patients was 97% (99% and 89% for PET2 negative and positive, respectively). Conclusion The PET-driven switch from ABVD to escalated BEACOPP is feasible and effective in high-risk patients with advanced-stage HL.

Between November 2012 and July 2014, in accordance with national law 648/96, brentuximab vedotin was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma outside a clinical trial context. A large Italian observational retrospective study was conducted on the use of brentuximab vedotin in everyday clinical practice to check whether clinical trial results are confirmed in a real-life context. The primary endpoint of this study was best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and safety profile. A total of 40 heavily pretreated patients were enrolled. Best response was observed after a median of four cycles in 77.5%: globally, 47.5% patients obtained a complete response, 64.2% in the elderly subset. The overall response rate was 62.5%. At the latest follow up, 15/18 patients are still in complete remission (3 with consolidation). The progression-free survival rate at 24 months was 39.1% and the disease-free survival rate at the same time was 54% (median not reached). All the long-term responders were aged

A large Italian multicenter observational retrospective study was conducted on the use of brentuximab vedotin (BV) for patients with relapsed Hodgkin's lymphoma (HL) to check if clinical trial results are confirmed even in a real life context. 234 CD30+ HL patients were enrolled. Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48.3% (62 CR and 51 PR). The best response rate was higher in the elderly subset: 14 (50%) CR and 5 (17.8%) PR. Disease free survival was 26.3% at 3 years and progression free survival 31.9% at 4.5 years. Duration of response did not differ for who achieved at least PR and then either did or did not undergo consolidative transplant. Overall, the treatment was well tolerated and no death has been linked to BV-induced toxicity. Our report confirms activity in elderly patients, duration of response unrelated to the consolidation with transplant procedure, the relevance of the CR status at first restaging, and the role of BV as a bridge to transplant for chemorefractory patients.

Background: Hodgkin Lymphoma (HL) is characterized by an inflammatory background and it has been demonstratedthat the reactive myeloid cells may exert an immune suppressive effect that favors progression of disease. The easily measurable NLR, the ratio between absolute neutrophils counts (ANC) and absolute lymphocyte count (ALC) and LMR, the ratio between ALC and absolute monocyte count (AMC) have been reported to reflect both the systemic inflammation and the myeloid associated immune suppression. We previously identified NLR, and to a lesser extend LMR, at baseline, as predictor of progression free survival (PFS) in HL patients. Objectives: To validate NLR>6 and LMR≤2 as predictor of clinical outcome at diagnosis in the context of a prospective clinical trial of newly diagnosed advanced stage (aa) HL patients treated upfront with a PET-2 risk-adapted strategy. Methods: According to HD 0607 trial (Gallamini, JCO 2018), 782 advanced-stage HL patients were treated with 2 ABVD courses and a PET-2 performed afterwards. PET-2 positive (PET-2+) patients (N=149) were randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4+4 courses) or Be+Bb (4+4) and Rituximab. PET-2 negative (PET-2-) patients were treated with 4 additional ABVD and, upon CR achievement, randomized to either consolidation radiotherapy on the sites of initial bulky disease or no further treatment. PET scans were centrally reviewed by an expert panel by Blinded Independent Central Review. Results: Median NLR at baseline was 5.7 (IQ range 3.8-8.3). NLR was higher in younger patients (7 cm, p6 in 88/149 (59%) PET-2+ and in 269/628 (43%) PET-2- patients. By univariate and multivariate analysis, bulky disease, IPS≥3, NLR>6 were strong independent predictors of early PET-2 response after ABVD (table I). Only PET-2 positivity (p Focusing on PET-2 negative patients, we found that patients with NLR>6 had an inferior 3-years PFS compared to patients with NLR ≤6 (84% versus 89%, p=0.003), while there was no stastical difference based on LMR status. Conclusion: At diagnosis, the presence of bulky disease, IPS score ≥3 and NLR>6 are independent predictors of early ABVD response (PET-2 positivity) and this information should be considered when selecting the initial treatment for aaHL patients. Disclosures Di Raimondo: Celgene: Honoraria; Takeda: Honoraria, Research Funding. Trentin:Janssen: Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; Gilead: Research Funding. Gallamini:Takeda: Consultancy, Speakers Bureau. Rambaldi:Amgen Inc.: Consultancy; Celgene: Consultancy; Roche: Consultancy; Italfarmaco: Consultancy; Omeros: Consultancy; Pfizer: Consultancy; Novartis: Consultancy.

From November 2012 to July 2014, brentuximab vedotin (BV) was available in Italy for patients with relapsed systemic anaplastic large cell lymphoma (ALCL) outside a clinical trial context based on a local disposition of the Italian Drug Agency (AIFA) issued according to a national law (Law 648/96: "medicinal products that are provided free of charge on the national health service"). A large Italian observational retrospective study was conducted on the use of BV in the everyday clinical practice to check if clinical trial results are confirmed even in a real life context. Primary endpoint was the best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and the safety profile. BV was infused intravenously at the dose of 1.8 mg/kg every 3 weeks for a maximum of 16 cycles. A total of 40 ALCL (18 anaplastic lymphoma kinase [ALK] negative and 22 ALK-positive status) patients were treated with BV in 40 Hematology Centers. All patients had histologically documented CD30+ ALCL; 16 (40%) had relapsed and 24 (60%) had refractory disease. Patients were heavily pretreated with a median of 2 previous therapies (including autologous transplant in the 32.5% of cases). Best response was observed after a median of 4 cycles in 31 patients (77.5%): 19 (47.5%) patients obtained a complete response (CR) and 12 (30%) achieved a partial response (PR); overall response rate at the end of the treatment was 62.5% (18 CR and 7 PR). The best response rate was higher in the elderly subset (>60 years): 9 (64.2%) CR and 3 (21.4%) PR, achieving a total of 85.6%. At the latest follow up 15/18 patients are still in CR (3 with consolidative procedure). Global progression free survival was 39.1% at 29 months and disease free survival 54% at 23.9 months (median not reached). Median duration of response was 12 months (range 9-24 months). We identified 5 long term responders (patients with a response ≥ 12 months), all were still in CR at the latest follow up (1 underwent allogeneic transplant). Particularly, all the long term responders were aged All patients were included in the safety profile for the analysis; in general, the treatment was well tolerated even in this real life context and the toxicity profile was closely similar to the previously published data; no death has been linked to BV toxicity. Toxicity was primarily neurological and rarely so serious as to require treatment reduction or interruption; furthermore, neurological toxicity always reversed completely after end of treatment. No long-term toxicity was assessed during the follow-up period, even in patients later subjected to transplant consolidation. BV induces clinical responses quite rapidly, i.e. within the first 4 cycles in most responders, thus permitting the timely application of the transplantation phase. Furthermore, BV displays a favorable toxicity profile, without overlapping toxicities with most of the agents employed in high-dose conditioning regimens. For patients ineligible for transplant or for who transplant failed, BV may represent a feasible effective therapeutic option in everyday clinical practice. Disclosures Rusconi: Takeda: Consultancy; Teva: Consultancy, Other: Congress attendance; Janssen: Consultancy, Other: Congress attendance. Spina:Mundipharma: Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fee; Teva Pharmaceuticals Industries: Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fee. Zinzani:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celegene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees.

From November 2012 to July 2014, brentuximab vedotin (BV) was available in Italy for patients with relapsed Hodgkin's lymphoma (HL) outside a clinical trial context based on a local disposition of the Italian Drug Agency (AIFA) issued according to a national law (Law 648/96: "medicinal products that are provided free of charge on the national health service"). A large Italian observational retrospective study was conducted on the use of BV in the everyday clinical practice to check if clinical trial results are confirmed even in a real life context. Primary endpoint was the best response; secondary endpoints were the overall response rate at the end of the treatment, duration of response, survival and the safety profile. BV was infused intravenously at the dose of 1.8 mg/kg every 3 weeks. A total of 234 HL patients were treated in 40. All patients had histologically documented CD30+ HL; 49% had relapsed and 51% had refractory disease. Patients were heavily pretreated with a median of 3 previous therapies (including autologous stem cell transplant [SCT] in the 69% of cases). Best response was observed after a median of 4 cycles in 140 patients (59.8%): 74 (31.6%) patients obtained a complete response (CR) and 66 (28.2%) achieved a partial response (PR); overall response rate at the end of the treatment was 48.3% (62 CR and 51 PR). The best response rate was higher in the elderly subset (>60 years): 14 (50%) CR and 5 (17.8%) PR. Disease free survival was 26.3% at 29 months and progression free survival 31.9% at 55 months. We identified 30 long term responders (patients with a response ≥ 12 months) of whom 18 are still in CR, 7 with a consolidative SCT and 11 without any consolidative procedure. Duration of response did not differ who achieved at least PR and then either did or did not undergo consolidative SCT. All patients were included in the safety profile for the analysis; in general, the treatment was well tolerated in everyday clinical practice and the toxicity profile was closely similar to the previously published data; no death has been linked to BV-induced toxicity. This preliminary analysis could indicate that BV displays a number of features favoring its use as a bridge to transplant in patients with active disease who achieve a suboptimal response to salvage treatment. Even in a real life context, BV induces clinical responses quite rapidly, i.e. within the first 4 cycles in most responders, thus permitting the timely application of the transplantation phase. BV displays a favorable toxicity profile, without overlapping toxicities with most of the agents employed in high-dose conditioning regimens. Furthermore, for HL patients ineligible for transplant or for who transplant failed, may represent a feasible effective therapeutic option. Disclosures Rusconi: Janssen: Consultancy, Other: Congress attendance; Teva: Consultancy, Other: Congress attendance; Takeda: Consultancy. Spina:Teva Pharmaceuticals Industries: Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fee; Mundipharma: Membership on an entity's Board of Directors or advisory committees, Other: Speaker Fee. Zinzani:Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celegene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees.

Abstract 550 Background: Interim FDG-PET performed after 2 chemotherapy courses (PET-2) is the most powerful predictor of treatment outcome in advanced-stage, ABVD-treated HL (AAHL) patients (pts). Whether early therapy intensification in PET-2 positive HL pts improves overall treatment efficacy for all AAHL pts compared to standard ABVD is still unproven. Patients and study design: In the HD 0607 clinical trial (ClinicalTRial.gov identifier 00795613), AHL (stage IIB-IVB) pts prospectively enrolled by 26 Italian and one Israelian institution are treated with 2 ABVD courses and a PET-2 performed afterwards. PET-2+ pts are randomized to either BEACOPP escalated (Be) plus BEACOPP baseline (Bb) (4+4 courses) or Be+Bb (4+4) and Rituximab (R). PET-2 negative pts are treated with 4 additional ABVD and, upon CR achievement, randomized to either consolidation radiotherapy (Rxt) on the sites of initial bulky disease or no further treatment. Primary endpoint is the efficacy and feasibility of the overall therapeutic strategy. All the non-negative PET-2 (nnPET-2), defined as scans without any residual FDG uptake in any site outside the physiological areas of the tracer concentration, are uploaded in a website for blinded independent central review (BICR) by 6 nuclear medicine experts. Scans are interpreted by visual assessment according to the Deauville 5-point scale (5PS). Results: Starting from 07/2008 till 07/2012, 497 AHL pts were consecutively enrolled and 446 scanned with PET-2. 189/446 (42%) PET-2scans, judged as nnPET-2 by the local PET center, underwent review: 92 were adjudged as positive (62 score 4, 30 score 5) and 97 as negative (score 1–3). Altogether, of 446 pts scanned with a PET-2, 92 (20%) resulted positive and 354 (80%) negative. Age, sex, stage III-IV, bulky, extranodal sites or IPS class where equally distributed among PET-2 positive and negative pts.(p>.05). The median time from PET uploading in the website to review was 45.38 hours, (1–119). The BICR yielded a binary concordance rate among pair of reviewers “very good”, ranging from 0.77 to 0.83 (Cohen's k coefficient) and a overall concordance rate of 0.77 (Krippendorf's alpha). In 92 PET-2+ pts, 60 showed a single site of residual uptake in mediastinal (48), laterocervical (4), supraclavear (2), abdominal (3), axillary (1) nodes and in lung (2).In 32 there were ≥ 2 sites of persistent FDG uptake. In 38/40 pts with a positive PET-2 and bulky disease at baseline the residual FDG uptake (singe or multifocal) was seen within the bulky lesion. Overall response to treatment could be assessed in a cohort of 263 pts who had been fully restaged after lymphoma treatment. Forty-one (15%) had a positive and 222 (84%) a negative PET-2 scan. The relative dose intensity (RDI) for Be+Bb ± R and ABVD ± RxT treated pts. was 94.7% and 97.8%, respectively. Among 41 PET-2+ pts CR was achieved in 30 (73%), PR in 1 (2%) Progression or Relapse (Pro/Rel) in 8 (19%) and not evaluable (NE) in 2(5%). Among 222 PET-2- pts. CR was achieved in 212 (95.5%), PR in 2 (1%), Pro/Rel in 6 (3%), NE in 1 (0,5%). Treatment efficacy could be assessed in a cohort of 187 pts. with a complete treatment and a minimum follow-up of 12 months from treatment completion: 27 (15%) with a positive PET-2, treated with Be+Bb ± R and 160 (85%) with a negative PET-2, treated with ABVD ± RxT. The median follow-up from diagnosis was 845 days (101–1345). Among 27 PET-2+ pts, CCR (Continuous CR) was recorded in 22 (81%) Pro/Rel in 5 (18%). Three patients died in CR: 2 for septic shock and one for pneumonia. Among 160 PET-2- pts. CCR was recorded in 146 (91%), Pro/Rel in 9 (5%), Lost of FU (in CR) in 5 (3%). The 1-y PFS was 80.5%, 97.3% and 94.7% for PET-2+, PET-2- p, and for the entire population, respectively. Overall, treatment was well tolerated: 512 Adverse effects were reported: WHO grade 0+1: 453, grade 2: 45. Grade 3 were observed in 12 pts: anemia (2), neutropenia (6), pancytopenia (1), sepsis (1), diverticulitis (1), Vomiting (1). Grade 4 in 2 pts: pneumonia and neutropenia. Conclusions: These preliminary findings suggest that 1) an early switch from ABVD to escalated BEACOPP can be done safely in PET-2 positive pts, with CR achievement in the majority of cases; 2) a centralized online PET scan review system is feasible and allows a real time decision making process, without significant reduction in the RDI administered; 3) 5PS is a reliable interpretation criteria for interim PET scan, with a very good concordance rate among reviewers. Disclosures: No relevant conflicts of interest to declare.