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PURPOSE 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) is currently the standard technique to define minimal residual disease (MRD) status outside the bone marrow (BM) in patients with multiple myeloma (MM). This study aimed to define criteria for PET complete metabolic response after therapy, jointly analyzing a subgroup of newly diagnosed transplantation-eligible patients with MM enrolled in two independent European randomized phase III trials (IFM/DFCI2009 and EMN02/HO95). PATIENTS AND METHODS Two hundred twenty-eight patients were observed for a median of 62.9 months. By study design, PET/CT scans were performed at baseline and before starting maintenance (premaintenance [PM]). The five-point Deauville scale (DS) was applied to describe BM (BM score [BMS]) and focal lesion (FL; FL score [FS]) uptake and tested a posteriori in uni- and multivariable analyses for their impact on clinical outcomes. RESULTS At baseline, 78% of patients had FLs (11% extramedullary), 80% with an FS ≥ 4. All patients had BM diffuse uptake (35.5% with BMS ≥ 4). At PM, 31% of patients had visually detectable FLs (2% extramedullary), 24% and 67.7% of them with an FS of 3 and ≥ 4, respectively. At PM, 98% of patients retained residual BM diffuse uptake, which was significantly lower than at baseline (mainly between BMS 2 and 3, BMS was ≥ 4 in only 8.7% of patients). By both uni- and multivariable analysis, FS and BMS < 4 were associated with prolonged progression-free survival (PFS) and overall survival (OS) at PM (OS: hazard ratio [HR], 0.6 and 0.47, respectively; PFS: HR, 0.36 and 0.24, respectively) CONCLUSION FL and BM FDG uptake lower than the liver background after therapy was an independent predictor for improved PFS and OS and can be proposed as the standardized criterion of PET complete metabolic response, confirming the value of the DS for patients with MM.

12068 Background: Current emphasis for childhood and young adults with HL is to maintain high cure rates while concurrently identifying regimens to reduce excess long-term mortality/morbidity. Thus, understanding the late effects (LE) of contemporary clinical trials (CCT) for HL is critical. Methods: We used simulation to estimate the projected life expectancy (LExp), quality adjusted life-expectancy (QALE) & cause of death (COD) in a large cohort of HL CCT patients (pts) in the recently established HoLISTIC consortium by linking long-term risk models from the SJLIFE cohort. Individual patient data (IPD) on bleomycin, alkylating agents and anthracycline were extracted & harmonized for 982 HL pts in 5 prospective CCT (mean diagnosis age 19y, range 3-30y; 51% male; all treated with chemotherapy only; progression-free survival [PFS] >5y) in the HoLISTIC database. LExp, QALE & COD were projected using a previously developed microsimulation model (Bhakta, Blood [Supplement], 2019) that incorporated mortality & incidence of LEs by diagnosis age, sex, race, treatment exposures & attained age estimated from 5,522 adult 10-y survivors of childhood cancers in the SJLIFE cohort (56% male; mean age at last follow-up 35y, range 19-68). Microsimulation was applied to 10,000 randomly selected survivors of HL CCT cohort, from 10y after HL diagnosis until death to project the LExp, QALE & COD. Results: Assuming 10-y PFS, LExp and QALEs projected for the HL CCT cohort using adjusted US general population rates linked with the SJLIFE microsimulation model, COD and trial-specific exposures are shown in the Table. Conclusions: A novel lifetime simulation approach was used to project LExp, QALE & COD by linking together IPD from CCTs with the long-term risk model of the SJLIFE survivorship cohort. Despite differences in PFS, reflecting in part the variation in risk/stage status, the projected long-term outcomes were similar. Our approach highlights a new opportunity to inform future clinical trial design and aid provider & patient decision-making. [Table: see text]

e20019 Background: Decision making in HL is complicated by clinical trial results that differ, a growing range of treatment options, and the absence of ideal, objective information on long term outcomes from modern therapy. Methods: We formed an international consortium, HoLISTIC, consisting of 50+ pediatric & adult HL providers, decision scientists, statisticians, epidemiologists, and patient (pt) advocates and are creating a data repository of individual pt data (IPD) from 16 contemporary, pediatric & adult clinical trials for newly diagnosed pts with HL, and 6 large HL registries/survivorship cohorts, the latter enriched with LE data (Table). We will enhance our prior decision model (DM) from group-level data (Parsons S et al. B J Haem 2018) to establish a dynamic HL DM from IPD. Using statistical and simulation modeling of IPD, the enhanced DM will project outcomes of interest, including quality-adjusted life years (QALYs), reflecting both mortality and morbidity. Results will be validated and calibrated against prominent external cohorts (e.g., St. Jude LIFE Cohort, Dutch HL registry). The DM then will be converted to a web-based platform that we will test and evaluate among HL providers and pts at the point of care. Results: To date, we have harmonized IPD from 10 trials (~8,000 HL pts), ranging in size from 165-1925 pts. At diagnosis, median age was 26 y (IQR 18-38); 51.5% were male. 43% had B symptoms, 34% had mediastinal bulk, and 79% had nodular sclerosis histology. Median follow up was 5.0 y (IQR 3.5-7.4). IPD harmonization is ongoing, which will be followed by creation of the enhanced DM. Conclusions: HoLISTIC capitalizes on a multidisciplinary pediatric & adult oncology collaborative, harmonizing extensive IPD by linking data from clinical trials and real world registries/survivorship cohorts. This work will inform questions about the influence of Tx options on both acute and potential long term events and how those options align with pt values and preferences. [Table: see text]

8029 Background: Hodgkin Lymphoma (HL) treatment in the elderly is a challenge, as standard ABVD is able to cure no more than 60% of the patients (p.). Bendamustine (Be), and Brentuximab Vedotin (BV), are well-tolerated and effective drugs in relapsing HL, but only preliminary data exist in 1st line treatment of the elderly (Evens AM 2018). Methods: HALO is a prospective international multicenter open-label phase I/II study (NCT02467946) to assess the safety and efficacy of Be-BV in advanced-stage elderly HL p. Briefly, BV 1.2 mg/kg on D1, and Be 90 mg/m2 on D1-2 were administered Q3W for 6 cycles. The primary endpoint was the feasibility and the efficacy of Be-BV. Results: Between July 2015 and February 2019, 59/60 p. consecutive enrolled received at least 1 Be-BV cycle, and are valuable for primary endpoint. One p. was excluded because a histological review showing angioimmunoblastic T-Cell Lymphoma. The mean age was 70.32 (62-79), and M/F ratio 41/18. The Ann-Arbor stage was IIB in 12, III in 14 and IV in 33 patients, B-symptoms (y/n) 40/19. IPS was 0-2 in 19 and ≥ 3 in 40 p., P.S. (ECOG) was 0-1 in 53, 2 in 6 p., nonetheless most of them were frail, as ADL was ≥ 6 in 47 (79%) and IADL was ≥ 8 in 42 (71%) p. Most frequent co-morbidities were cardio-vascular disease (45) metabolism disorders (31) prostatic adenoma (11). 163 treatment-related adverse events (WHO 3-4) were recorded: neutropenia and lymphopenia, (134), infections (7), cutaneous reactions (5), liver toxicity (2). No case of grade > 2 peripheral neuropathy was recorded. Out of 59 p., 41 concluded and 18 interrupted the treatment for toxicity (8), progression (5), treatment failure (2), CMV reactivation (3). The latter was recorded in 17 p., 12/17 received valgancyclovir. 4 p. died with CMV viremia. After a mean follow-up of 20.6 (0.3-46.5) months, 37/59 (63%) were in CR, while 22 (37%) have progressed (5) or relapsed (17). The 2-y OS and PFS in ITT analysis were 83% (95% CI 71-96) and 54% (95% CI 41-72) and in PP 89% (95%CI 75-100) and 78% (95%CI 64-96), respectively. 22 p. had a PFS event: 5 progression (2 deaths), 17 relapse (8 deaths). 10 p. died for recurrent HL (5), sepsis (1), secondary malignancy (2), respiratory insufficiency (1) and unknown (1). Conclusions: The Be-BV combination, a novel anthracycline-free regiment for first line treatment of HL in elderly, proved effective in unselected, frail, poor-risk, HL p. aged more than 60 in daily hospital real life. The CMV reactivation is frequent and should be treated with preemptive antiviral therapy upon detection of CMV DNA in plasma. Clinical trial information: NCT02467946 .

Purpose [18F]Fluorodeoxyglucose positron emission tomography (PET) is widely used for the staging and restaging of patients with aggressive lymphoma, but less is known about the utility of PET in patients with follicular lymphoma (FL). In a prospective study, we evaluated the prognostic value of PET performed during treatment and at the end of treatment in 121 patients with FL treated with first-line immunochemotherapy. Patients and Methods Patients with previously untreated high–tumor burden FL were treated with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) plus two cycles of rituximab, without rituximab maintenance. PET was performed before treatment, after four cycles of R-CHOP (interim PET), and at the end of treatment (final PET). PET scans were centrally reviewed. Results The total number of patients included was 121. Median age was 57 years. After central review, interim PET (n = 111) was negative in 76% of patients, and final PET (n = 106) was negative in 78%. With a median follow-up of 23 months, 2-year progression-free survival rates were 86% for interim PET–negative versus 61% for interim PET–positive patients (P = .0046) and 87% for final PET–negative versus 51% for final PET–positive patients (P < .001), respectively. Two-year overall survival also significantly differed according to final PET results: 100% versus 88% (P = .0128). Conclusion PET performed either after four cycles of R-CHOP or at the end of therapy was strongly predictive of outcome in this prospective study. Therapeutic intervention based on PET results during or after inductive treatment should be evaluated.

7534Background: ECHELON-1 is a phase 3 study of BV plus doxorubicin, vinblastine, and dacarbazine (A+AVD) vs ABVD as frontline therapy in untreated advanced HL (NCT01712490). G-CSF primary prophyla...

7539Background: The ECHELON-1 trial demonstrated improved outcomes for patients (pts) with advanced HL who received frontline A+AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) vs A...

TPS8612 Background: Brentuximab vedotin, a CD30-targeted antibody-drug conjugate, has conditional approval in Europe for relapsed/refractory (RR) CD30-positive HL following autologous stem cell tra...

TPS8612 Background: Brentuximab vedotin, a CD30-targeted antibody-drug conjugate, has conditional approval in Europe for relapsed/refractory (RR) CD30-positive HL following autologous stem cell transplant (ASCT) or following ≥2 prior therapies when ASCT or multi-agent chemotherapy is not a treatment option. ABVD, a common front-line regimen for advanced HL, achieves complete response (CR) rates of 70–80%. However, 10–20% of patients (pts) are refractory to front-line treatment and up to 35% relapse after front-line multi-modality therapy. In pts with relapsed HL post-ASCT, single-agent brentuximab vedotin yields an objective response rate of 75% (CR, 33%; Chen ASH 2012). In a phase 1 study in treatment-naïve HL pts, A+AVD was associated with manageable toxicity and a CR rate of 96%; brentuximab vedotin + ABVD was contraindicated due to pulmonary toxicity (Ansell ASH 2012). We hypothesized that substituting bleomycin with brentuximab vedotin would eliminate bleomycin-associated pulmonary toxicity and improve progression-free survival (PFS) compared to a standard ABVD regimen. Methods: This ongoing, open-label, randomized, multicenter study (NCT01712490) will compare A+AVD vs ABVD in 1040 pts with stage III/IV classical HL. Primary endpoint: modified (m) PFS (death, progression, and receipt of chemotherapy or radiotherapy by pts not in CR after completing A+AVD or ABVD will count as progression event). Key secondary endpoint: overall survival. Key inclusion criteria: histologically-confirmed previously untreated stage III/IV classical HL. Pts will be stratified by region and International Prognostic Score, and will be randomized 1:1 to receive A+AVD (brentuximab vedotin 1.2 mg/kg with each dose of AVD) or ABVD administered intravenously on Days 1 and 15 of 28-day cycles, for up to 6 cycles. Disease status and survival will be evaluated regularly until study closure. Safety assessments: incidence and severity of adverse events, changes to physical and laboratory tests. Clinical trial information: NCT01712490.

e13093 Background: Recently a novel clinical trial generation based on a therapeutic strategy driven by early treatment response assessment to therapy by functional imaging was conceived and a central review of the images became necessary. We describe hear the application of a new web-based tool for imaging exchange and online review of PET scan (WIDEN) conceived for the prospective multicenter clinical trial HD0607. Methods: In the HD 0607 clinical trial 367 patients affected by advanced-stage Hodgkin Lymphoma (HL), are treated with 2 ABVD courses and a PET scan performed afterwards (PET-2). PET-2 positive patients shift to an aggressive treatment, PET-2 negative patients continue with ABVD. PET-2 along with the baseline scan (PET-0) is uploaded to a dedicated web site thanks to WIDEN and hence distributed to six expert reviewers. The latter report the scans within 72 hours from the upload and determine the choice whether intensify or not the treatment intensity (NCT identifier 00795613). Results: The average (median) time per scan upload and download were 6’39” (1’35”) and 3’26” (1’53”) respectively. The average (median) PET scan size were 133.8 MB (121.5 MB), with a minimum size of 51.2 MB and a maximum size of 469.8 MB. The average (median) time frame between the case files upload by the submitting centre and the case review reporting was 48h 45‘ (40h 31’). 7% of the cases were reviewed among the forth and the fifth days. 3% cases were reviewed after the fifth days. In all cases of a review time spanning over more than three days the delay depended on the presence of a week-end of other holiday time. Concordance rate among reviewers measured with Krippendorff,s alpha was 0.799. Conclusions: WIDEN proved to be an effective tool for medical imaging exchange and review. Data security, simplicity, low cost, feasibility and prompt scan review were demonstrated. Its applicability in any clinical trial in which imaging is decisional for treatment modulation is warranted

8006 Background: Early interim 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) performed after two ABVD courses (PET2) is the most reliable prognosticator in advanced-stage Hodgkin lymphoma (AS-HL) patients (pt.). We evaluated retrospectively the results of a therapeutic strategy based on early chemotherapy (CT) intensification with BEACOPP in PET2 positive (PET2+) in AS-HL. Methods: Between January 2006 and December 2007 164 newly diagnosed HL pt. consecutively admitted to 8 Italian and 1 American centers sharing this PET response adapted strategy were enrolled. Results: Prognostic factors were well-balanced between PET2+ and PET2- pt. (p= 0.14-0.89). In 97/164 pt. (59%) PET2 scans underwent central review (CREw) according to a 5-point semiquantitative score with the liver as reference organ for FDG uptake. (Meignan 2009). In 90/97 pt. CREw confirmed the PET2 interpretation of the local PET center (LOPc). Four pt. with a PET2- by LOPc, reclassified as PET2+, showed CT failure after...

8058 Background: Recent reports suggest that medical imaging, besides potentially harmful, could turn out neither cost- effective, nor beneficial. We investigated whether this can be justified in t...

6687 Background: At present CHOP plus rituximab (CHOP-R) appears to be the golden standard treatment for elderly patients with diffuse large B-cell lymphoma (B-DLCL). Treatment related toxicity, in...

Plasma cell acid phosphatase (AP) activity and thymidine labeling index (LI%) were evaluated concomitantly in 52 patients with monoclonal gammopathies. AP score, percentage of AP positive plasma cells, and LI% were significantly higher in 26 patients with multiple myeloma (MM) at the time of diagnosis than in 11 monoclonal gammopathy of undetermined significance (MGUS) and eight smoldering myeloma (SM) patients. LI% had the highest statistical correlation with disease status. A 1% cutoff could clearly separate the patients with progressive MM compared to those with stable disease (SM-MGUS) (P less than .001). There was a significant overall correlation between the AP score and LI% (P less than .005). Since LI% is a recognized powerful prognostic factor, this correlation suggests that the AP score can also be a reliable test predicting patient survival duration. In addition, we identified a subgroup of IgG MM patients with very high tumor mass who had a low LI% but a high AP score. This was associated with very poor patient survival and indicated the discrete prognostic importance of AP score in this subgroup with low LI%. Thus, both the LI% and AP score can be recommended as helpful clinical tests in patients with monoclonal gammopathies.