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Purpose: We conducted a phase II study evaluating pembrolizumab plus gemcitabine, vinorelbine, and liposomal doxorubicin (pembro-GVD) as second-line therapy for relapsed or refractory (rel/ref) classical Hodgkin lymphoma (cHL) (ClinicalTrials.gov identifier: NCT03618550)., Methods: Transplant eligible patients with rel/ref cHL following first-line therapy were treated with two to four cycles of pembrolizumab (200 mg intravenous [IV], day 1), gemcitabine (1,000 mg/m 2 IV, days 1 and 8), vinorelbine (20 mg/m 2 IV, days 1 and 8), and liposomal doxorubicin (15 mg/m 2 , days 1 and 8), given on 21-day cycles. The primary end point was complete response (CR) following up to four cycles of pembro-GVD. Patients who achieved CR by labeled fluorodeoxyglucose-positron emission tomography (Deauville ≤ 3) after two or four cycles proceeded to high-dose therapy and autologous hematopoietic cell transplantation (HDT/AHCT). HDT/AHCT was carried out according to institutional standards, and brentuximab vedotin maintenance was allowed following HDT/AHCT., Results: Of 39 patients enrolled, 41% had primary ref disease and 38% relapsed within 1 year of frontline treatment. 31 patients received two cycles of pembro-GVD, and eight received four cycles. Most adverse events were grade 1 or two, whereas few were grade 3 and included transaminitis (n = 4), neutropenia (n = 4), mucositis (n = 2), thyroiditis (n = 1), and rash (n = 1). Of 38 evaluable patients, overall and CR rates after pembro-GVD were 100% and 95%, respectively. Thirty-six (95%) patients proceeded to HDT/AHCT, two received pre-HDT/AHCT involved site radiation, and 13 (33%) received post-HDT/AHCT brentuximab vedotin maintenance. All 36 transplanted patients are in remission at a median post-transplant follow-up of 13.5 months (range: 2.66-27.06 months)., Conclusion: Second-line therapy with pembro-GVD is a highly effective and well-tolerated regimen that can efficiently bridge patients with rel/ref cHL to HDT/AHCT., Competing Interests: Alison J. MoskowitzHonoraria: Seattle GeneticsConsulting or Advisory Role: Seattle Genetics, Takeda, Imbrium Therapeutics, Merck, Janpix, Kyowa Kirin International, miRagen, ADC Therapeutics, Bristol Myers SquibbResearch Funding: Incyte, Seattle Genetics, Merck, Bristol Myers Squibb, miRagen, ADC Therapeutics, BeiGene Gunjan ShahResearch Funding: Janssen, Amgen Anita KumarStock and Other Ownership Interests: BridgebioConsulting or Advisory Role: Celgene, Kite, a Gilead company, AstraZeneca/MedImmuneResearch Funding: AbbVie/Genentech, Adaptive Biotechnologies, Celgene, Seattle Genetics, AstraZeneca/MedImmune, Pharmacyclics Oscar LahoudConsulting or Advisory Role: MorphoSysTravel, Accommodations, Expenses: MorphoSysOpen Payments Link: https://openpaymentsdata.cms.gov/physician/225358/summary Connie L. BatleviStock and Other Ownership Interests: Moderna Therapeutics, Novavax, Pfizer, Bristol Myers Squibb, Regeneron, ViatrisHonoraria: DAVAOncologyConsulting or Advisory Role: Lifesci Capital, GLG, Juno Therapeutics, Celgene, Seattle Genetics, Kite, a Gilead company, TG Therapeutics, Karyopharm TherapeuticsResearch Funding: Janssen Biotech, Novartis, Epizyme, Xynomic Pharma, Bayer, Roche, AutolusOpen Payments Link: https://openpaymentsdata.cms.gov/physician/2778694 Paul HamlinConsulting or Advisory Role: Juno Therapeutics, Karyopharm Therapeutics, Celgene, Sandoz, AstraZeneca/MerckResearch Funding: Spectrum Pharmaceuticals, Seattle Genetics, Janssen, Portola Pharmaceuticals, GlaxoSmithKline, Molecular Templates, Incyte David J. StrausConsulting or Advisory Role: Takeda, Seagen, EpizymeResearch Funding: Takeda Ildefonso Rodriguez-RiveraStock and Other Ownership Interests: Pfizer Philip CaronStock and Other Ownership Interests: AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Johnson & Johnson/Janssen, Novartis, Pfizer, Teva Steven M. HorwitzConsulting or Advisory Role: Celgene, Millennium, Kyowa Hakko Kirin, Seattle Genetics, ADC Therapeutics, Verastem, Takeda, Astex Pharmaceuticals, Kura Oncology, Acrotech Biopharma, C4 Therapeutics, Janssen Oncology, Trillium Therapeutics, Vividion Therapeutics, Myeloid Therapeutics, Ono Pharmaceutical, Secura Bio, Shoreline Biosciences Inc, TubulisResearch Funding: Celgene, Seattle Genetics, Takeda, Kyowa Hakko Kirin, Aileron Therapeutics, ADC Therapeutics, Verastem, 47, Trillium Therapeutics, Daiichi Sankyo, Affimed Therapeutics, Secura Bio Lorenzo FalchiConsulting or Advisory Role: GenmabResearch Funding: Roche, Genmab Erel JoffeConsulting or Advisory Role: AstraZeneca, Epizyme Christina LeeHonoraria: WebMDConsulting or Advisory Role: Intellisphere LLC M. Lia PalombaStock and Other Ownership Interests: Seres TherapeuticsHonoraria: Flagship Biosciences, Evelo Therapeutics, Jazz Pharmaceuticals, Therakos, Amgen, Merck, Seres TherapeuticsConsulting or Advisory Role: Flagship Biosciences, Novartis, Evelo Therapeutics, Jazz Pharmaceuticals, Therakos, Amgen, Merck, Seres Therapeutics, Kite, a Gilead company, Novartis, BeiGeneResearch Funding: Seres TherapeuticsPatents, Royalties, Other Intellectual Property: Intellectual Property Rights, Juno intellectual property rights Ariela NoyConsulting or Advisory Role: MorphoSys, Janssen Biotech, Prime OncologyResearch Funding: Pharmacyclics, Rafael PharmaceuticalsTravel, Accommodations, Expenses: Pharmacyclics, Janssen Oncology Matthew J. MatasarStock and Other Ownership Interests: MerckHonoraria: Genentech, Roche, Bayer, Pharmacyclics, Seattle Genetics, Takeda, Immunovaccine, ADC Therapeutics, Karyopharm TherapeuticsConsulting or Advisory Role: Genentech, Bayer, Merck, Juno Therapeutics, Roche, Teva, Rocket Medical, Seattle Genetics, Daiichi Sankyo, TakedaResearch Funding: Genentech, Roche, GlaxoSmithKline, Bayer, Pharmacyclics, Janssen, Rocket Medical, Seattle Genetics, Immunovaccine, IGM BiosciencesTravel, Accommodations, Expenses: Genentech, Roche, Seattle Genetics, Bayer Georgios PongasHonoraria: Atara Biotherapeutics, Curio Science, OncLive/MJH Life SciencesTravel, Accommodations, Expenses: Atara Biotherapeutics Gilles SallesHonoraria: Roche/Genentech, Janssen, Celgene, Gilead Sciences, Novartis, AbbVie, MorphoSysConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Janssen, Celgene, Novartis, MorphoSys, Epizyme, Alimera Sciences, Genmab, Debiopharm Group, Velosbio, BMS, BeiGene, Incyte, Miltenyi Biotec, Ipsen Santosha VardhanaHonoraria: AgiosConsulting or Advisory Role: Immunai, ADC Therapeutics Gottfried von KeudelllHonoraria: PharmacyclicsConsulting or Advisory Role: Pharmacyclics, Merck, Incyte Ahmet DoganConsulting or Advisory Role: Seattle Genetics, Takeda, EUSA Pharma, AbbVie, Peerview, Physicans' Education ResourceResearch Funding: Roche/Genentech Andrew D. ZelenetzHonoraria: NCCN, Clinical Care Options, Oncology Information Group, PER, PlexusConsulting or Advisory Role: Gilead Sciences, Amgen, Genentech/Roche, Celgene, AstraZeneca, DAVAOncology, MorphoSys, BeiGene, MEI Pharma, Vaniam Group, Verastem, Pharmacyclics, Karyopharm Therapeutics, Debiopharm Group, Seattle Genetics, Quant Health Ltd, Kite, a Gilead company, Curis, Coherus Biosciences, Juno/Celgene/Bristol Myers Squibb, Curio ScienceResearch Funding: Genentech/Roche, Gilead Sciences, MEI Pharma, BeiGene Craig H. MoskowitzConsulting or Advisory Role: Merck Sharp & Dohme, Molecular Templates, Takeda, AstraZeneca, IncyteResearch Funding: AstraZeneca, Merck Sharp & DohmeNo other potential conflicts of interest were reported.

Background: The increased risk of cancer in patients with sarcoidosis is well established, but there is little information regarding sarcoid diagnosed during or following cancer. The purpose of this study is to describe and analyze the disease status and events associated with the diagnosis of sarcoid in cancer patients., Methods: At a large cancer center, we identified 64 patients with a pathologic diagnosis of sarcoid-like granuloma during or following a diagnosis of malignancy. Pathology specimens were re-examined by experts, and clinical and imaging information were reviewed. Disease-related events including recurrence, progression, death, and second malignancy were analyzed., Results: The most common primary malignancies were breast (17%), lymphoma (16%), lung (13%), and testicular cancer (11%). Thirty-six out of 64 patients (56%) were diagnosed with sarcoid within 10 months of their primary malignancy, whereas 28 (44%) were diagnosed with sarcoid in follow-up, including 15/28 without evidence of disease, 6 with associated diagnosis of recurrence, 5 with associated diagnosis of second malignancy, 1 with stable disease, and 1 with progressive disease. Sarcoid biopsy sites included mediastinal nodes (59%), hilar nodes (13%), lung (30%), and other nodes (17%), and the reason for biopsy was usually abnormal imaging (66%). Sarcoid and tumor were co-localized in 34%. Including long-term follow-up events, sarcoid was present in association with 10 of 19 recurrences (53%) and 8 of 12 second malignancies (67%)., Conclusion: While sarcoid often presents at initial diagnosis or staging of cancer, in a significant number of patients, it appears in association with recurrence or second malignancy.

Background: Pre-transplantation (18)F-fluorodeoxyglucose (FDG) PET-negativity is one of the strongest predictors of outcome after high-dose therapy and autologous stem-cell transplant (HDT/ASCT) for patients with relapsed or refractory Hodgkin's lymphoma. In this study, we assessed the feasibility and activity of PET-adapted salvage therapy with brentuximab vedotin, followed by augmented ifosfamide, carboplatin, and etoposide (ICE)., Methods: In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients with relapsed or refractory Hodgkin's lymphoma who had failed one previous doxorubicin-containing chemotherapy regimen. All patients received weekly infusions of 1·2 mg/kg brentuximab vedotin on days 1, 8, and 15 for two 28 day cycles. After completion of brentuximab vedotin treatment, patients received a PET scan. Patients who achieved PET-negative status (a Deauville score of 1 or 2) proceeded directly to HDT/ASCT; those with persistent abnormalities on PET received two cycles of augmented ICE (augICE; two doses of ifosfamide 5000 mg/m(2) in combination with mesna 5000 mg/m(2) continuous infusion over 24 h, days 1 and 2; one dose of carboplatin AUC 5, day 3; three doses of etoposide 200 mg/m(2) every 12 h, day 1) before consideration for HDT/ASCT. Only patients with persistent abnormalities on PET after brentuximab vedotin received augICE; however, all patients in the intention-to-treat population were assessed for the primary outcome, which was the proportion of patients who were PET-negative after brentuximab vedotin alone or brentuximab vedotin followed by augICE. This study is registered with ClinicalTrials.gov, number NCT01508312, and is no longer accruing patients., Findings: Between Jan 5, 2012, and Oct 4, 2013, we enrolled 46 patients. One patient was deemed ineligible, and not evaluable, before treatment initiation owing to having nodular, lymphocyte-predominant Hodgkin's lymphoma and thus 45 patients received treatment. After brentuximab vedotin, 12 patients (27%, 95% CI 13-40) were PET-negative and proceeded to HDT/ASCT. 33 (73%, 95% CI 60-86) patients were PET-positive after brentuximab vedotin; one PET-positive patient withdrew consent, therefore 32 PET-positive patients received augICE, 22 (69%, 95% CI 53-85) of whom were PET-negative. Overall, 34 patients (76%, 95% CI 62-89) achieved PET-negativity. All 44 patients who completed treatment as per protocol proceeded to receive HDT/ASCT. Brentuximab vedotin was well tolerated and associated with few grade 3-4 adverse events including hyperglycaemia (two [4%] patients, grade 3), nausea (one [2%], grade 3), hypoglycaemia (one [2%], grade 3 and one [2%], grade 4), and hypocalcaemia (one [2%], grade 3 and one [2%], grade 4)., Interpretation: PET-adapted sequential salvage therapy with brentuximab vedotin followed by augICE resulted in a high proportion of patients with relapsed or refractory Hodgkin's lymphoma achieving PET-negativity, and therefore could optimise the chance of cure after HDT/ASCT., Funding: Seattle Genetics., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: To evaluate the risk of late morbidity and mortality, and to assess long-term health-related quality of life (QOL) among patients with relapsed/refractory Hodgkin's lymphoma (HL) after high-dose chemoradiotherapy (HDT) and autologous stem-cell rescue (ASCR)., Patients and Methods: From 1985 to 1998, 218 patients with HL were treated on HDT with ASCR salvage protocols. Of these 218, 153 (70%) who survived > or = 2 years after ASCR were evaluated for late morbidity and mortality from causes other than HL. QOL information was obtained through self-administered questionnaires. Risk ratios (RR) were calculated to compare observed second malignancy (SM) rates in this cohort with expected SM rates from the Surveillance Epidemiology and End Results (SEER) registry., Results: Median follow-up after ASCR was 11.5 years. Among 153 patients, there were 53 deaths; 33 from HL and 20 from other causes. Thirteen deaths were caused by SM, with median time from ASCR to SM diagnosis of 9 years (range, 3 to 18 years). The RR of SM was 6.5 (95% CI, 3.6 to 10.7) when compared with the general population, but 2.4 (95% CI, 1.4 to 4.05) when compared with patients with HL. Global QOL of ASCR survivors was comparable with the general population, but for specific domains, respondents' scores indicated reduced functioning and worse symptoms., Conclusion: HL accounts for most deaths among patients surviving HDT and ASCR. Survivors of ASCR had an elevated risk of SM compared with the cancer risk in the general population, but when compared with patients with HL in SEER, the risk was less pronounced.

To define the incidence and spectrum of pulmonary complications following autologous bone marrow transplantation (BMT), we retrospectively reviewed the course of 77 consecutive patients with Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) who failed conventional therapy and underwent autologous BMT. Forty-five percent of the 77 patients developed respiratory complications with a mortality from pulmonary causes of 26%. A total of 38 episodes of respiratory compromise occurred in 35 patients. Infections accounted for 15 episodes (39%) and included bacterial (16%), Aspergillus (8%) cytomegalovirus (8%), Herpes simplex (3%), and other (5%) pneumonias. The spectrum of infections was similar to that reported following allogeneic BMT, but cytomegalovirus pneumonia was not as frequent a problem in those with autologous transplant. Mortality from pulmonary infections was 33%. Noninfectious disorders accounted for 23 episodes (61%) and included recurrent HD (18%), radiation/drug toxicity (16%), and acute respiratory failure thought secondary to pulmonary alveolar hemorrhage (26%). This latter entity developed acutely within 2 wk following BMT and was associated with use of thoracic radiation for treatment of malignant disease in the chest just prior to BMT (p < 0.05). It was not associated with the age of the patient or presence of thrombocytopenia, coagulopathy, renal insufficiency or neutropenia (p NS). Mortality from noninfectious causes was 65%, but in those with pulmonary hemorrhage it was 100%. In conclusion, pulmonary complications are a major source of morbidity and mortality in patients with HD and NHL undergoing autologous BMT.(ABSTRACT TRUNCATED AT 250 WORDS)