Stephens, Deborah M.

The treatment landscape of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has significantly evolved in recent years. Targeted therapy with Bruton’s tyrosine kinase (BTK) inhibitors and BCL-2 inhibitors has emerged as an effective chemotherapy-free option for patients with previously untreated or relapsed/refractory CLL/SLL. Undetectable minimal residual disease after the end of treatment is emerging as an important predictor of progression-free and overall survival for patients treated with fixed-duration BCL-2 inhibitor-based treatment. These NCCN Guidelines Insights discuss the updates to the NCCN Guidelines for CLL/SLL specific to the use of chemotherapy-free treatment options for patients with treatment-naïve and relapsed/refractory disease.

Abstract Introduction: Bruton tyrosine kinase inhibitors (BTKi) have revolutionized the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and certain B-cell neoplasms. However, resistance to BTKi develops primarily through mutations at the cysteine binding site (C481) or PLCγ2 mutations. MK-1026 (formerly ARQ-531) is a non-covalent, potent inhibitor of both wild type and C481- mutated BTK. In the phase 1/2 dose escalation and dose expansion study NCT03162536, the preliminary recommended phase 2 dose (RP2D) of MK-1026 was determined to be 65 mg once daily. The efficacy and safety of MK-1026 in participants with CLL/SLL and B-cell non-Hodgkin lymphoma (NHL) were also evaluated at a higher dose during the dose expansion phase. Methods: In this open-label, single-arm phase 2 study, 9 expansion cohorts were initiated following determination of preliminary MK-1026 RP2D. Approximately 10-25 eligible participants were enrolled into Cohort A (relapsed/refractory (r/r) CLL/SLL, with ≥2 prior therapies including covalent BTKi, with documented C481 mutation), Cohort B (r/r CLL/SLL progressed on/intolerant to a BTKi, with ≥2 prior therapies without C481 mutation), Cohort C (participants with Richter transformation [RT] with ≥1 prior therapy), Cohort D-H (participants with follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), high-grade B cell lymphoma (BCL) with known MYC, BCL-2 or BCL-6 translocations, and Waldenström macroglobulinemia (WM), respectively, who received ≥2 prior therapies), Cohort I (food effect cohort including participants with B-cell NHL, CLL/SLL, and WM). Treatment continued until unacceptable toxicity, clinical or radiological progression, participant/physician withdrawal. Primary endpoint was overall response rate (per iwCLL criteria, by investigator) for participants with CLL/SLL. Secondary endpoints included duration of response and safety and tolerability. The data cut-off date for this analysis was April 7, 2021. Results: Among 118 participants enrolled, 44 had B-cell NHL (including 6 with DLBCL, 11 with FL, 3 with high-grade BCL, 6 with MCL, 2 with MZL, 16 with RT), 68 CLL/SLL, and 4 WM. Of these, 94 (79.6%) were treated at the preliminary RP2D, including 51 (54.3%) participants with CLL/SLL. Participants with CLL/SLL had a median (range) number of prior therapies of 4 (1-18), 43 (84%) had prior BTKi therapy, 12 (23%) had del17p, 26 (51%) had IGHV unmutated status, and 32 (63%) had C481S BTK mutation. At data cut-off, median (range) follow-up was 4.56 months (0.1-26.7) for all treated participants. ORR was 57.9% (N = 22 of 38; 1 CR, 21 PR/PRL) per iwCLL criteria in the efficacy evaluable population of participants with CLL/SLL treated at preliminary RP2D. The median duration of response in these participants was not estimable [NE] (range, 8.3 months-NE). At data cut-off, the median duration of treatment exposure was 3.2 months (range, 0-35.9). Among all treated participants, 114 (97%) had a treatment-emergent adverse event (TEAE), with 78 (66%) having a drug-related TEAE, and 9 (8%) having a drug-related TEAE that led to discontinuation. Common TEAEs (≥ 20%) included fatigue (33%), constipation (31%), dysgeusia (28%), cough (25%), nausea (25%), pyrexia (25%), dizziness (23%), hypertension (23%), peripheral edema (22%), arthralgia (20%), and diarrhea (21%). Grade ≥3 TEAEs occurred in 80 (68%) participants. Grade 5 TEAEs occurred in 7 (6%) participants and included death following disease progression in 3 (3%), sepsis 1 (1%), dyspnea 1 (1%), and respiratory failure 2 (2%) participants. Common drug-related TEAEs (≥10%) included dysgeusia (15%), nausea (11%), fatigue (11%), and decreased neutrophil count (10%). Grade 3-4 drug-related TEAEs occurred in 31 (26%) participants. No drug-related TEAEs led to death. Conclusion: MK-1026 has promising antitumor activity with a manageable safety profile in participants with CLL/SLL exposed to multiple lines of therapy, including in those who had progression of disease on prior covalent BTKi. Further evaluation of MK-1026 in B-cell malignancies is ongoing. Disclosures Woyach: AbbVie Inc, ArQule Inc, Janssen Biotech Inc, AstraZeneca, Beigene: Other: Advisory Committee; AbbVie Inc, ArQule Inc, AstraZeneca Pharmaceuticals LP, Janssen Biotech Inc, Pharmacyclics LLC, an AbbVie Company,: Consultancy; AbbVie Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Research Funding; Gilead Sciences Inc: Other: Data & Safety. Flinn: Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Awan: Verastem: Consultancy; Incyte: Consultancy; Dava Oncology: Consultancy; MEI Pharma: Consultancy; Beigene: Consultancy; Celgene: Consultancy; Johnson and Johnson: Consultancy; Karyopharm: Consultancy; Kite pharma: Consultancy; Gilead sciences: Consultancy; Pharmacyclics: Consultancy; Janssen: Consultancy; BMS: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy; ADCT therapeutics: Consultancy; Abbvie: Consultancy; Astrazeneca: Consultancy; Genentech: Consultancy. Eradat: AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Speakers Bureau; Juno: Research Funding; Kite: Research Funding; Genentech: Research Funding. Brander: Pfizer: Consultancy, Other: Biosimilars outcomes research panel; Juno Therapeutics/Celgene/Bristol Myers Squibb: Research Funding; ArQule: Research Funding; Ascentage: Research Funding; AstraZeneca: Research Funding; BeiGene: Research Funding; DTRM: Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; MEI Pharma: Research Funding; TG Therapeutics: Consultancy, Research Funding; Novartis: Research Funding; LOXO: Research Funding; Verastem: Consultancy; ArQule/Merck: Consultancy; Genentech: Consultancy, Research Funding; NCCN: Other: panel member; AbbVie: Consultancy, Other: informCLL registry steering committee, Research Funding. Parikh: Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Bristol Myers Squibb, Merck, AbbVie, and Ascentage Pharma: Research Funding; Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie: Membership on an entity's Board of Directors or advisory committees. Phillips: BMS: Consultancy, Research Funding; AstraZeneca: Consultancy; Incyte: Consultancy, Other: received travel expenses from Incyte, Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; ADCT, BeiGene, Bristol Myers Squibb, Cardinal Health, Incyte, Karyopharm, Morphosys, Pharmacyclics, Seattle Genetics: Consultancy; Bayer: Consultancy, Research Funding. Reddy: Merck & Co., Inc.: Current Employment. Farooqui: Merck & Co., Inc.: Current Employment, Other: Current Stockholder. Byrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees. Stephens: CSL Behring: Consultancy; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; Beigene: Membership on an entity's Board of Directors or advisory committees; Epizyme: Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Arqule: Research Funding; Mingsight: Research Funding; JUNO: Research Funding; Novartis: Research Funding; Abbvie: Consultancy; AstraZeneca: Consultancy; Celgene: Consultancy; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding.

PURPOSEDiffuse large B-cell lymphoma (DLBCL) presents as a limited-stage disease in 25% to 30% of patients, with better overall survival (OS) than that for advanced-stage disease but with continuous relapse regardless of treatment approach. The preferred treatment is abbreviated rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and radiation therapy. On the basis of promising results of positron emission tomography (PET)–directed treatment approaches, we designed a National Clinical Trials Network (NCTN) study to improve outcomes and decrease toxicity.METHODSPatients with nonbulky (< 10 cm) stage I/II untreated DLBCL received 3 cycles of standard R-CHOP therapy and underwent a centrally reviewed interim PET/computed tomography scan (iPET). Those with a negative iPET proceeded with 1 additional cycle of R-CHOP, whereas those with a positive iPET received involved field radiation therapy followed by ibritumomab tiuxetan radioimmunotherapy.RESULTSOf 158 patients enrolled, 132 were eligible and 128 underwent iPET, which was positive in 14 (11%) of the patients. With a median follow-up of 4.92 years (range, 1.1-7.7 years), only 6 patients progressed and 3 died as a result of lymphoma. Eleven patients died as a result of nonlymphoma causes at a median age of 80 years. The 5-year progression-free survival estimate was 87% (95% CI, 79% to 92%) and the OS estimate was 89% (95% CI, 82% to 94%), with iPET-positive and iPET-negative patients having similar outcomes.CONCLUSIONTo our knowledge, S1001 is the largest prospective study in the United States of limited-stage DLBCL in the rituximab era, with the best NCTN results in this disease subset. With PET-directed therapy, 89% of the patients with a negative iPET received R-CHOP × 4, and only 11% had a positive iPET and required radiation, with both groups having excellent outcomes. The trial establishes R-CHOP × 4 alone as the new standard approach to limited-stage disease for the absolute majority of patients.

Introduction Limited stage disease accounts for 30-40% of Diffuse Large B-cell Lymphoma (DLBCL), with better overall survival than advanced stage disease, but with increased late relapses regardless of treatment strategy (Stephens 2016). Preferred treatment for these patients (pts) per NCCN guidelines is abbreviated R-CHOP followed by radiotherapy. Based on promising results of radioimmunotherapy consolidation in SWOG S0313 (Persky 2015), and of PET-directed experience by the BC Cancer Agency (Sehn 2011), we designed a National Clinical Trials Network (NCTN) PET-directed study to tailor therapy after 3 cycles of R-CHOP, to improve outcomes and decrease toxicities. Methods Pts had non-bulky (&lt; 10 cm) stage I/II untreated DLBCL. Mediastinal, HIV-associated, testicular, central nervous system, and indolent lymphoma were excluded. Pts received standard R-CHOP therapy and had an interim PET scan on day 15-18 of cycle 3, which was centrally reviewed in real time. Pts with negative PET scan (Deauville 1-3, iPET-neg) proceeded with 1 additional cycle of R-CHOP. Pts with positive PET scan (Deauville 4-5, iPET-pos) initiated 36 Gy of involved field radiation therapy (IFRT), plus additional boost to FDG-avid area up to 9 Gy, within 5 weeks of 3rd cycle of R-CHOP. This was followed by ibritumomab tiuxetan (IFRT-Zevalin) 3-6 weeks after completing IFRT. Final PET scan was performed 12 weeks after treatment completion. Results The study completed accrual in June 2016. Safety, response, interim PET, and immunohistochemistry-based cell of origin (COO) and MYC/BCL2 analyses were presented previously (Persky 2017, Stephens 2017). Of 159 pts enrolled, 1 was upstaged by PET, and 26 pts were ineligible - due to incorrect histology (mostly concurrent indolent or follicular lymphoma grade 3B) (21), lack of diagnostic tissue submission for central pathology review (3), and bulky disease (2). In 132 eligible pts, median age was 62 years, 62% had stage I, 17% had B symptoms, 14% had elevated LDH, 43% had extranodal involvement, and 66% had exclusive involvement of the head and neck region. Stage modified IPI (smIPI, Miller 1998) was 0 in 27%, 1 in 42%, 2 in 28%, and 3 in 4% of the pts. COO by Lymph2Cx was assessable in 87 pts - 68% were GCB, 23% were ABC, and 9% were unclassifiable. Double protein expressers (MYC and BCL2, DPE) were 16%, while 4 (3%) pts had "double hit" lymphoma (DHL) - 2 with MYC/BCL2 and 2 with MYC/BCL6 rearrangements - none of which were DPE. Of 132 eligible pts, 128 had an interim PET scan centrally reviewed, of which 110 were iPET-neg. Only 18 were iPET-pos, 4 of them due to infection (Deauville X) which were treated as iPET-neg. Of 14 truly iPET-pos pts (11%), 2 refused radiation, and 12 pts received IFRT-Zevalin. Eight pts (67%) converted from PR to CR after IFRT-Zevalin and 4 (33%) had PR, for an overall CR of 92% and PR of 4% (with 4% unevaluable). With median follow up of 4.5 yrs (range 1.1 - 7.5 yrs), only 5 pts progressed and 2 died from lymphoma. Of 5 progressors, 3 received R-CHOP x 4, 1 was iPET-pos but declined radiation, and 1 went off treatment after 1 cycle of R-CHOP. Eleven pts died from non-lymphoma causes, including 1 pt from secondary AML (iPET-neg arm), and 1 of lung adenocarcinoma diagnosed upon iPET. S1001 5-yr PFS estimate is 87% and OS estimate is 90% (figure 1), with iPET-pos and iPET-neg pts having similar outcomes - PFS 86% vs. 88%, OS 93% vs. 91%, respectively. Five-yr PFS by smIPI was 97% for smIPI of 0, 86% for 1-2, and 30% for 3. GCB had 5-yr PFS of 95%, vs. 70% for ABC and 47% for unclassifiable. DPE pts had 5-yr PFS of 70, vs. 89% for non-DPE pts. All 4 DHL pts maintain remission. Conclusions S1001 is the largest US study of limited stage DLBCL in the rituximab era, with best NCTN results in this disease subset. Only 5 patients progressed and 2 died from lymphoma. Our study confirms the distinct biology of limited stage DLBCL, with predominance of GCB origin (68%), and head and neck location (66%). Due to small number of lymphoma events, no strong conclusions about prognostic ability of smIPI, COO, DPE, or DHL, could be made. S1001 demonstrated that 89% of pts maintained excellent outcomes after R-CHOP x 4 with PET-directed therapy. Only 11% of pts were iPET-pos and required radiation, but they also had excellent outcomes. Together with the FLYER trial in younger pts (Poeschel 2018), this NCTN trial establishes R-CHOP x 4 alone as the new standard approach to limited stage disease for majority of the pts. Disclosures Persky: Sandoz: Consultancy; Morphosys: Other: Member, Independent Data Monitoring Committee; Debiopharm: Other: Member, Independent Data Monitoring Committee; Bayer: Consultancy. Stephens:Acerta: Research Funding; Karyopharm: Research Funding; Gilead: Research Funding. Park:BMS: Consultancy, Research Funding; Rafael Pharma: Membership on an entity's Board of Directors or advisory committees; G1 Therapeutics: Consultancy; Teva: Consultancy, Research Funding; Gilead: Speakers Bureau; Seattle Genetics: Research Funding, Speakers Bureau. Bartlett:Seattle Genetics: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Pfizer: Research Funding; Millenium: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Genenetech: Research Funding; Immune Design: Research Funding; Gilead: Research Funding; Forty Seven: Research Funding; Janssen: Research Funding; Affimed: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding. Swinnen:Pharmacyclics: Consultancy; AbbVie: Consultancy. Barr:Celgene: Consultancy; Merck: Consultancy; Seattle Genetics: Consultancy; Genentech: Consultancy; Verastem: Consultancy; Gilead: Consultancy; Astra Zeneca: Consultancy, Research Funding; Janssen: Consultancy; AbbVie: Consultancy; Pharmacyclics LLC, an AbbVie company: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding. Leonard:Nordic Nanovector: Consultancy; Akcea Therapeutics: Consultancy; BeiGene: Consultancy; Gilead: Consultancy; Miltenyi: Consultancy; ADC Therapeutics: Consultancy; Nordic Nanovector: Consultancy; Akcea Therapeutics: Consultancy; Sandoz: Consultancy; ADC Therapeutics: Consultancy; Miltenyi: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy; Karyopharm Therapeutics: Consultancy; Epizyme, Inc: Consultancy; Sutro Biopharma: Consultancy; AstraZeneca: Consultancy; AstraZeneca: Consultancy; Bayer Corporation: Consultancy; Bayer Corporation: Consultancy; Celgene: Consultancy; Epizyme, Inc: Consultancy; Celgene: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy; Merck: Consultancy; MorphoSys: Consultancy; Karyopharm Therapeutics: Consultancy; Gilead: Consultancy; Sutro Biopharma: Consultancy; BeiGene: Consultancy; Merck: Consultancy; MorphoSys: Consultancy; Sandoz: Consultancy. Kahl:TG Therapeutics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy; BeiGene: Consultancy. Fisher:Celgene: Consultancy; AstraZeneca: Consultancy; Barclays: Honoraria; prIME: Honoraria. Rimsza:NanoSting: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution]. Smith:Portola Pharmaceuticals: Research Funding. Friedberg:Bayer: Honoraria, Other: Data & Safety Monitoring Committee; Acerta: Other: Data & Safety Monitoring Committee. OffLabel Disclosure: Ibritumomab tiuxetan in diffuse large B-cell lymphoma

Abstract Introduction: Given the availability of several active treatment (tx) options for CLL, providers frequently make tx recommendations based on their interpretation of objective data from consensus criteria and clinical trials. There are limited data describing patient (pt) experience, values, and insights when encountering multiple tx choices. The CLL Society, a pt-driven, physician-curated nonprofit organization focused on the unmet needs of the CLL community, sought to explore how CLL pts make tx decisions. Methods: A 64 question survey was distributed online and in paper to CLL pts from Oct-Dec 2017. The survey was developed by CLL experts. The research was IRB-approved. Chi square was used for statistical comparison; all other analyses are descriptive in nature. Results: 1147 pts from 48 states completed the survey. Median age was 65 (range 28-86), 46% male, 96% Caucasian. Who Influences Tx: Of the 79% of pts who have seen a CLL expert, defined as a provider focused on CLL at an academic/research center, 95% rated their provider as very/extremely influential. 83% of pts rated their own opinions as influential, and 59% rated the opinion of a general hematologist/oncologist (gen heme/onc), a provider who sees a variety of cancer types, as influential. Only 27% let their provider unilaterally decide on tx. Of these pts, 19% trusted their provider to select the best tx and 5% didn't have enough understanding to be involved in the decision. 64% were influenced by outside sources of information, such as family members, live CLL support groups, or online sources including pt experts and forums. Factors in Deciding Tx: Of the 67% pts surveyed who have been treated, 73% were offered > 1 tx choice by their provider. In deciding on a specific tx, 94% of respondents stated that it was very/extremely important to know there were tx options beyond their current regimen. The most important factors in selecting tx were response rate (91%), overall survival (88%), progression-free survival (86%), long-term side effects (82%), ability to achieve undetectable MRD (80%), cost/insurance coverage (66%), and location of tx (50%) with significant differences between subgroups (Table 1). Tx was impacted by cost or insurance issues for 16% (n=104). Of these 104 pts, cost/insurance issues resulted in tx delay for 34 and change in tx plan for 24 pts. 16 pts reported that an appeal led to coverage and 16 pts received financial assistance. Pts' willingness to accept potentially curable but high-risk tx was heavily influenced by availability of alternate options. For example, 18% of pts would be willing to consider cytotoxic chemotherapy if alternate options were available vs. 72% if no options were available. Similar patterns were seen with CAR-T tx (28% vs. 79%) and bone marrow transplantation (BMT) (15% vs. 66%) with significant differences between subgroups (Table 2). 82% were willing to take a life-long tx for long-term control without potential for cure. Willingness to accept long-term tx was significantly higher in treated vs. untreated pts (84% vs. 77%, p=.006) and men vs. women (84% vs. 78%, p=.008). Clinical Trial Education: Of those treated by a gen heme/onc, 31% received no education on clinical trials. Only 15% reported good understanding of trial opportunities vs. 52% treated by a CLL expert (p<.001). 9% of pts treated by gen heme/onc were offered clinical trial participation vs. 47% treated by a CLL expert (p<0.001). Pts who declined or would have declined participation cited reasons including preference for "proven" tx (38%), distance from trial site (29%), fear (20%), frequent imaging (20%), overall lack of understanding about trials (15%), and lack of information (14%). Summary: Most respondents want to be and are involved in tx decisions. While providers are influential in decision making, CLL pts also rely on outside sources. Gender, age, and tx status influence which factors drive decision making. Pts select tx based on response rate, survival, side effects, and ability to achieve deep response and want a plan in place for sequencing tx. The majority are willing to consider long-term tx without cure. Few want chemotherapy, CAR-T, or BMT unless they have no other options. A significant opportunity for improvement in education on clinical trial opportunities was identified. This description of pt experience, values, and preferences enriches the informed consent process and may lead to more tailored and patient-centered care. Disclosures Kennard: AbbVie, Gilead, Verastem: Consultancy. Furman:TG Therapeutics: Consultancy; Loxo Oncology: Consultancy; Sunesis: Consultancy; Verastem: Consultancy; Incyte: Consultancy, Other: DSMB; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Gilead: Consultancy; Janssen: Consultancy; Pharmacyclics LLC, an AbbVie Company: Consultancy; AbbVie: Consultancy. Pagel:Pharmacyclics, an AbbVie Company: Consultancy; Gilead: Consultancy. Davids:Sunesis: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Consultancy, Research Funding; Surface Oncology: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Merck: Consultancy; Merck: Consultancy; MEI Pharma: Consultancy, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Consultancy, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Research Funding; Surface Oncology: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Roche: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Verastem: Consultancy, Research Funding; BMS: Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Surface Oncology: Research Funding; Verastem: Consultancy, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sunesis: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy; Roche: Consultancy. Nabhan:Cardinal Health: Employment, Equity Ownership. Kay:Acerta: Research Funding; Tolero Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Morpho-sys: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios Pharm: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Infinity Pharm: Membership on an entity's Board of Directors or advisory committees; Cytomx Therapeutics: Membership on an entity's Board of Directors or advisory committees. Siddiqi:Juno Therapeutics: Other: Steering committee. Brander:Genentech: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Teva: Consultancy, Honoraria; Novartis: Consultancy, Other: DSMB; TG Therapeutics: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; BeiGene: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Acerta: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; DTRM: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding. Wierda:AbbVie, Inc: Research Funding; Genentech: Research Funding. Hill:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cheson:AbbVie, Roche/Genentech, Pharmacyclics, Acerta, TG Therapeutics: Consultancy. Choi:Pharmacyclics: Consultancy, Research Funding, Speakers Bureau; Gilead: Speakers Bureau; Rigel: Consultancy; Genentech: Speakers Bureau; AbbVie, Inc: Consultancy, Speakers Bureau. Mato:AstraZeneca: Consultancy; Prime Oncology: Honoraria; Portola: Research Funding; Johnson & Johnson: Consultancy; Medscape: Honoraria; Celgene: Consultancy; TG Therapeutics: Consultancy, Research Funding; Acerta: Research Funding; Pharmacyclics, an AbbVie Company: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Regeneron: Research Funding.

Abstract Introduction For patients with Stage III/IV Hodgkin lymphoma (HL), lack of response as assessed by PET scan following cycle 2 (PET2) of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is predictive of poor clinical outcomes. SWOG Study S0816 utilized response-adapted therapy, where patients achieving a complete remission (CR) on PET2 (Deauville Score ≤ 3) continued 4 additional cycles of ABVD and those patients unable to achieve a complete remission (CR) on PET2 (Deauville Score > 3) were switched to therapy with escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (eBEACOPP) for 6 cycles. This study demonstrated a 2-year PFS of 64% in the PET2+ patients after switching to eBEACOPP, which was much higher than expected (Press 2016). Herein, we report the 5-year follow-up of survival and toxicities of the patients treated on S0816. Methods Patients with Stage III/IV HL were enrolled to S0816 from 7/1/09-12/2/12 (n=358). Eligible patients were age 18-60 years, had measurable disease, no prior lymphoma therapy, a Zubrod performance status of 0-2, and no serious medical comorbidities. Patients were treated with response-adapted therapy as above. A subset of 336 eligible and HIV-negative patients were analyzed. Of 336, 331 had central review of PET2. PFS and OS estimates were calculated using the Kaplan-Meier method. The two-sided Fisher's exact test was used to compare the rate of second cancer between patients switched to treatment eBEACOPP and those treated with continued ABVD after 2 initial cycles of ABVD. Results The median age of patients was 32 years (range, 18-60). All were Stage III/IV and 51% had an International Prognostic Score of ≥ 3. PET2 was negative in 271 patients (82%) and positive in 60 patients (18%). Of PET2+ patients, 49 (82%) switched to eBEACOPP as planned and 11 (18%) declined. Median follow-up is now 5.9 years (range, 0.2-8.3 years). Eighty-five (25%) patients have either progressed or died, for an estimated 5-year PFS of 74% (95% CI: 69%-79%; Figure 1). There were 64 (24%) events in those patients who were PET2- for a 5-year PFS of 76% (95% CI: 71-81%; Figure 2). There were 20 (33%) events in those patients who were PET2+ for a 5-year PFS of 65% (95% CI: 51-76%; Figure 2). One event occurred in a patient without central review of PET2. Nineteen patients have died for an estimated 5-year overall survival of 94% (95% CI: 91%-96%; Figure 1). Eleven (3%) patients died of HL including 6 (2%) that had PET2- and 5 (8%) that had PET2+. Other causes of death included: treatment-related toxicity [sepsis (eBEACOPP n=1), bleomycin lung injury (eBEACOPP n=1; ABVD n=1), and graft versus host disease (ABVD n=1)]; second primary cancers [(eBEACOPP n=2; cervical cancer and non-Hodgkin lymphoma (NHL)]; and unknown causes (ABVD n=2). Post-therapy grade 3 adverse events were uncommon but included 1 case each of heart failure, peripheral neuropathy, prolonged neutropenia, diarrhea, DVT (catheter-related) in patients who received continued ABVD and osteonecrosis of hips/shoulders in patients who received eBEACOPP. There were 13 (4%) cases of reported second cancers, including 7 (14%) in patients treated with eBEACOPP [1 each of myelodysplastic syndrome, kidney, melanoma, NHL, cervical, medullary thyroid, and basal cell carcinoma] and 6 (2%) in patients treated with ABVD (1 each of kidney, melanoma, NHL, bladder, prostate, and squamous cell carcinoma; 2-sided Fisher's exact P value = 0.001). Conclusions The long-term overall survival of the patients treated on S0816 remains high (94%) at 5 years. Despite historical data suggesting favorable clinical outcomes in patients with a negative PET2, nearly 25% of these patients experienced relapse events, demonstrating limitations of a PET-adapted approach and of standard frontline therapy with ABVD. In patients who were PET2+, PFS was favorable relative to historical series, but was associated with a high rate of secondary malignancies. Our results emphasize the importance of long-term follow-up in this disease, and the need for better biomarkers at diagnosis of HL and less toxic approaches for patients with a positive PET2. Acknowledgment In memory of Oliver W. Press, principal investigator of this trial, who died in 2017. Disclosures Straus: DAVA Oncology: Consultancy, Honoraria; Medical Crossfire: Speakers Bureau; Millenium (Takeda): Consultancy, Research Funding; JUNO: Consultancy; Bayer: Consultancy; Onco Tracker: Consultancy; Seattle Genetics: Consultancy; Roch China: Speakers Bureau; InPractice Elselvier: Consultancy; Memorial Sloan Kettering Cancer Center: Employment. Rimsza:NanoString: Other: Inventor on the patent for the Lymph2Cx assay. Bartlett:ImaginAB: Research Funding; Genentech: Research Funding; Forty Seven: Research Funding; Bristol-Meyers Squibb: Research Funding; Merck & Co: Research Funding; Novartis: Research Funding; Celgene: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Research Funding; Millennium: Research Funding; Janssen: Research Funding; Affimed: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding. Evens:Janssen: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics International DMC: Membership on an entity's Board of Directors or advisory committees; Affimed: Consultancy; Abbvie: Consultancy; Novartis: Consultancy; Tesaro: Research Funding; Acerta: Consultancy. LaCasce:Seattle Genetics: Consultancy, Honoraria; Bristol-Myers Squibb: Other: Data safety and monitoring board; Research to Practice: Speakers Bureau; Humanigen: Consultancy, Honoraria. Barr:AbbVie, Gilead: Consultancy. Leonard:Gilead: Consultancy; Sutro: Consultancy; BMS: Consultancy; Juno: Consultancy; MEI Pharma: Consultancy; Celgene: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; AstraZeneca: Consultancy; Biotest: Consultancy; Novartis: Consultancy; Karyopharm: Consultancy; Genentech/Roche: Consultancy; ADC Therapeutics: Consultancy; United Therapeutics: Consultancy. Kahl:Genentech: Consultancy; Celgene: Consultancy; Acerta: Consultancy; AstraZeneca: Consultancy; Juno: Consultancy; CTI: Consultancy; ADC Therapeutics: Consultancy; Abbvie: Consultancy; Gilead: Consultancy; Seattle Genetics: Consultancy. Smith:BMS: Consultancy; Portola: Honoraria. Friedberg:Bayer: Honoraria.

Abstract Introduction Transformation of chronic lymphocytic leukemia (CLL) into Hodgkin lymphoma (HL) is a rare, but recognized complication of CLL. The prognosis of CLL with HL Transformation (HT) appears significantly worse than de novo HL, but most series are small and there are limited published data. These reports have prompted several groups to recommend aggressive therapy with stem cell transplantation (SCT) in first complete remission (CR1). We describe the largest reported series of HT patients (pts) with analyses of the clinicobiologic characteristics, treatment patterns, and clinical outcomes based upon our multi-institutional clinical experience. Methods Pts diagnosed with HT from 01/2000 - 01/2018 were retrospectively identified in 13 tertiary cancer centers. Clinicobiologic characteristics, treatment type, and survival outcomes for each pt were analyzed. Overall survival (OS) was measured from the time of HT diagnosis until time of death. OS estimates were calculated using the Kaplan-Meier method. The log-rank test was used to calculate differences in survival. Results Ninety-four pts with HT were identified. Median age at HT was 67 years (yrs; range, 38-85) and 81% of the pts were male. Median time from CLL diagnosis to HT was 5.5 yrs (range, 0-20.2; 7 pts with simultaneous diagnosis of CLL and HL). At initial CLL diagnosis, 31%, 34%, 21%, 10%, and 4% were Rai Stage 0, 1, 2, 3, and 4, respectively. At CLL diagnosis, 67% (25/37) had an un-mutated IgVH gene, 36% (21/59) had del(13q), 32% (14/44) had trisomy 12, 24% (14/59) had del(11q), and 15% (9/61) had del(17p). Prior to HT diagnosis, pts had a median of 2 (range, 0-12) therapies for CLL. Seventeen (18%) had no prior CLL treatments. Forty-three (46%) and 25 (27%) patients had received purine analogue- and ibrutinib-based therapy prior to HT, respectively. Baseline characteristics at HT are described in Table 1. As initial therapy for HL, the majority of pts (61%, n = 62) received ABVD-based regimens (adriamycin, bleomycin, vinblastine, and dacarbazine) at full (n = 48) or reduced (n = 14) doses. Of these, CD20 monoclonal antibody was added in 6 and Bruton-tyrosine kinase inhibitor was added in 2. Ten (11%) received a brentuximab-based regimen. Seven (7%) received an RCHOP-based regimen (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Six patients (6%) received no therapy for HT due to frailty. Subsequent therapy included autologous SCT and allogeneic SCT in 7 (7%) and 11 (12%) of patients, respectively. Two (2%) and 5 (5%) pts received their autologous and allogeneic SCT while in CR1, respectively. The median number of treatments for HT per pt was 1 (range, 0-5) with 59 (61%) pts only receiving one line of therapy. After HT diagnosis, pts had a median follow-up of 1.6 yrs (range, 0.0 - 15.1). Two-yr OS after HT diagnosis was 72% (95%CI 62 - 83%). The pts who received any CLL directed therapy (n = 80) prior to HT had a significantly lower estimated 2-yr OS of 69% (95%CI 58 - 82%) compared with pts who did not receive any prior CLL-directed therapy (n = 17; 93%; 95%CI 82-100%; p 0.02; Figure 1). Pts who received purine-analogue-based therapy for their CLL prior to HT had a significantly lower estimated 2-yr OS of 60% (95%CI 46 - 79%) compared with pts who did not receive purine-analogue-based CLL-directed therapy prior to HT (n = 51; 83%; 95%CI 73 - 96%; p 0.009; Figure 2). Although limited by small sample size, the pts who underwent SCT for HT in CR1 had a similar 2-yr OS (n = 7; 67%; 95%CI 38-100%) to pts who did not undergo SCT for HT in CR1 (n = 87; 72%; 95%CI 63 - 84%; p 0.46; Figure 3). Conclusions In this retrospective analysis, we describe the largest reported series of pts with HT from CLL. Two-yr survival in pts with HT was shorter than what is historically expected in patients with de novo HL, but longer than what is expected in CLL pts who transform to diffuse large B-cell lymphoma. Pts with HT who have received prior CLL-directed therapies (specifically purine-analogue-based treatments) are estimated to have a shorter 2-yr OS, likely due to underlying immunosuppression. The majority of pts (61%) only received 1 line of HL therapy and only 20% went on to receive SCT (7% while in CR1), indicating that these patients can have prolonged OS after achieving response to first-line therapy for HT and may not require SCT in CR1. Further study of this rare population is required to determine optimum management. Disclosures Kander: AstraZeneca: Consultancy. Parikh:Gilead: Honoraria; AstraZeneca: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Janssen: Research Funding; MorphoSys: Research Funding; Pharmacyclics: Honoraria, Research Funding. Shadman:Acerta Pharma: Research Funding; Verastem: Consultancy; Celgene: Research Funding; Gilead Sciences: Research Funding; Mustang Biopharma: Research Funding; Pharmacyclics: Research Funding; AstraZeneca: Consultancy; Beigene: Research Funding; Genentech: Research Funding; Qilu Puget Sound Biotherapeutics: Consultancy; AbbVie: Consultancy; TG Therapeutics: Research Funding; Genentech: Consultancy. Pagel:Pharmacyclics, an AbbVie Company: Consultancy; Gilead: Consultancy. Mato:Portola: Research Funding; AstraZeneca: Consultancy; Acerta: Research Funding; Prime Oncology: Honoraria; Regeneron: Research Funding; Celgene: Consultancy; Pharmacyclics, an AbbVie Company: Consultancy, Research Funding; Medscape: Honoraria; TG Therapeutics: Consultancy, Research Funding; Johnson & Johnson: Consultancy; AbbVie: Consultancy, Research Funding. Hill:Amgen: Research Funding; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Danilov:Verastem: Consultancy, Research Funding; Aptose Biosciences: Research Funding; Takeda Oncology: Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Astra Zeneca: Consultancy; Gilead Sciences: Consultancy, Research Funding. Phillips:Abbvie: Research Funding; Bayer: Consultancy; Gilead: Consultancy; Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy. Brander:Pharmacyclics, an AbbVie Company: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Acerta: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Novartis: Consultancy, Other: DSMB; Teva: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; DTRM: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; Genentech: Consultancy, Honoraria, Other: Institutional research funding for non investigator initiated clinical trial, Research Funding; BeiGene: Other: Institutional research funding for non investigator initiated clinical trial, Research Funding. Smith:BMS: Consultancy; Portola: Honoraria. Davids:Surface Oncology: Research Funding; Roche: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Surface Oncology: Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; MEI Pharma: Consultancy, Research Funding; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Verastem: Consultancy, Research Funding; Roche: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Research Funding; BMS: Research Funding; MEI Pharma: Consultancy, Research Funding; Abbvie: 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; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Consultancy; Merck: Consultancy; Celgene: Consultancy; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy; Celgene: Consultancy; BMS: Research Funding; Surface Oncology: Research Funding; MEI Pharma: Consultancy, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Research Funding.

AbstractThe investigators present results on the long-term value and limitations of early interim positron emission tomography (PET) scanning in advanced Hodgkin lymphoma.