APRIL 11-14, 2018 SWOG LYMPHOMA

LYMPHOMA COMMITTEE APRIL 11-14, 2018 SWOG LYMPHOMA 1

CONTENTS S0816 Phase II... 6 S1608 Phase II... 30 EAY131 Master Protocol / Phase II... 32 APRIL 11-14, 2018 SWOG LYMPHOMA 2

Patient Registrations to Studies By 12 Month Intervals LYMPHOMA COMMITTEE 350 300 304 140 250 200 150 100 50 0 53 84 27 Jan 2012 Dec 2012 121 37 38 39 Jan 2013 Dec 2013 79 24 29 Jan 2014 Dec 2014 SWOG LAPS MEMBER NCORP NON-SWOG 96 19 38 26 Jan 2015 Dec 2015 Time of Registration 42 25 Jan 2016 Dec 2016 7 Jan 2017 Dec 2017 Screening registrations and registrations to Biologic only studies are excluded. APRIL 11-14, 2018 SWOG LYMPHOMA 3

Patient Registrations by Study and Arm LYMPHOMA COMMITTEE Jul 2017 Dec 2017 Jan 2017 Jun 2017 Jul 2016 Dec 2016 All Patients S1001 DLBCL, I-II, PET-Adapted Therapy PET-Directed Therapy Continued R-CHOP 0 0 2 137 IFRT + Zevalin 0 0 1 12 A051301 ABC DLBCL, Auto HCT and Ibrutinib/Placebo* 0 0 3 149 Total Registrations 4 1 0 5 C51101 CNS, Myelo/non-Myelo Chemo, PhII* Total Registrations 0 1 3 9 E1411 MCL, RB+R, RBV+R, RB+LR, RBV+LR* Total Registrations 0 0 4 86 E1412 DLBCL, R2CHOP vs RCHOP* Total Registrations 0 1 3 39 * For non-swog coordinated studies only SWOG registrations are shown. APRIL 11-14, 2018 SWOG LYMPHOMA 4

Non-SWOG Studies with SWOG-Credited Registrations LYMPHOMA COMMITTEE Studies with Accrual from July 2016 - December 2017 SWOG Champion Date Activated Date Closed Total Accrued 9177 NHL, Dose-Adj. EPOCH+/-Rituximab M Fanale 04/13/12 05/10/17 164 No Progress Report Available A051301 ABC DLBCL, Auto HCT and Ibrutinib/Placebo P. Stiff 07/15/16 23 No Progress Report Available C51101 CNS, Myelo/non-Myelo Chemo, PhII N Mohile 06/22/12 05/02/17 113 Most Recent Progress Report E1411 MCL, RB+R, RBV+R, RB+LR, RBV+LR B Till 06/08/12 09/09/16 373 Most Recent Progress Report E1412 DLBCL, R2CHOP vs RCHOP J Amengual 01/22/14 01/24/17 349 Most Recent Progress Report EA4151 MCL, Auto-HCT+Rituximab vs. +Rituximab B Till 08/29/17 3 No Progress Report Available APRIL 11-14, 2018 SWOG LYMPHOMA 5

S0816 Phase II Coordinating Group: SWOG A Phase II Trial of Response-Adapted Therapy of Stage III-IV Hodgkin Lymphoma Using Early Interim FDG-PET Imaging Participants: SWOG, CTSU (Supported by AMC, Alliance, ECOG- ACRIN) Study Chairs: O Press, N Bartlett (Alliance), J Sweetenham (ECOG- ACRIN), M Lechowicz (AMC) Date Activated: 07/01/2009 Date Closed: 12/01/2012 Statisticians: H Li, M LeBlanc Data Coordinator: J Jardine SCHEMA R E G I S T E R ABVD X 2 PET- PET+ ABVD X 4 BEACOPP X 6* * HIV-negative patients will receive BEACOPP escalated * HIV-positive patients will receive BEACOPP standard Objectives The co-primary objectives are as follows: a. To estimate two-year progression-free survival (PFS) in HIV-negative patients with advanced stage Hodgkin lymphoma (HL) treated with responseadapted therapy based on FDG-PET imaging after two cycles of adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). b. To estimate two-year PFS in the subset of HIVnegative patients with advanced stage HL who are PET-positive after two cycles of ABVD and are subsequently treated with escalated dose BEACOPP. APRIL 11-14, 2018 SWOG LYMPHOMA 6

Secondary endpoints include the following: To estimate two-year overall survival (OS) for HIVnegative patients treated with response-adapted therapy. To estimate the response rate (complete and partial) for HIV-negative patients treated with responseadapted therapy. To evaluate the toxicity of this response-adapted regimen. To document the feasibility of centralized, real-time review of FDG-PET imaging for US cooperative group studies. To prospectively evaluate the overall response rate, complete response rate, PFS and OS in a cohort of HIV-positive patients with HL treated with responseadapted therapy. The use of cycle-2 PET scanning in HIV infection will be done to provide preliminary data for this strategy in HIV-infected patients. To prospectively identify serum and tissue biomarkers associated with PFS and OS in patients with HL treated with response-adapted therapy. Biologic features meriting specific investigation include the degree of tumor cell infiltration with T- regulatory cells, the FOXP3/Granzyme B ratio, and the expression of MAL or Bcl-2 in biopsy samples, and TARC levels in serum specimens. To prospectively evaluate HIV viral load and CD4 cells in the cohort of HIV-positive patients with HL treated with response-adapted therapy. Patient Population Patients must have histologically or cytologically confirmed classical Hodgkin lymphoma. Patients with nodular lymphocyte-predominant Hodgkin lymphoma are ineligible. Patients with CNS disease involvement are ineligible. Patients must not have received prior chemotherapy, radiation, or antibody therapy for lymphoma. Patients must have a Zubrod performance status of 0-2, be at least 18 and no more than 60 years of age, and have adequate cardiac and pulmonary function. Patients must not be sero-positive for Hepatitis B or C. HIV-positive patients are eligible if they do not have multi-drug resistant HIV infection, CD4 counts < 350/mcL or other concurrent AIDS-defining conditions. Stratification/Descriptive Factors Patients will be stratified by HIV-positivity: yes vs no. Accrual Goals As part of an amendment on August 1, 2011, the sample size for this study was increased. Patient accrual will continue until 60 eligible patients in the FDG-PET-positive subgroup are enrolled. Under the assumption that 17% of patients are FDG-PETpositive after two cycles of ABVD, this leads to a sample size of 350 eligible HIV-negative patients. The HIV-positive cohort will be analyzed separately, with maximum anticipated accrual of 30 eligible HIV-positive patients. Summary Statement This study was closed on December 1, 2012, after reaching full accrual. Three hundred seventy-one patients were registered to this study, including 358 HIV-negative patients and 13 HIV-positive patients. HIV-negative cohort: Of 358 HIV-negative patients, 20 patients are ineligible due to incorrect histology after centralized pathology review. Two additional patients who did not receive any protocol treatment are not analyzable and are excluded from all analyses. Two initial cycles of ABVD were completed as planned in 333 patients. Three patients discontinued the initial ABVD for the following reasons: one due to neutropenia, one refused treatment, and another one was non-compliant. Three hundred thirty-six HIV-negative patients were assessed for toxicity during the two initial cycles of ABVD. One hundred thirty-six patients experienced 4 toxicities, primarily hematologic. Of these, seven patients experienced the following 4 non-hematologic toxicities: blood infection (2 patients, coded as "Inf, 3-4 ANC: blood"), febrile neutropenia, abdomen pain (coded as "GI pain: abdomen"), lung infection (coded as "Lung inf, 3-4 ANC: mucosa"), chest wall pain (coded as "Lung Pain: chest wall"), agitation, depression, and nausea (1 patient each). Ninety-two patients experienced 3 toxicities as maximum degree. APRIL 11-14, 2018 SWOG LYMPHOMA 7

Among 336 evaluable patients who received two initial cycles of ABVD, eight patients who did not have response adequately assessed are assumed nonresponders for the purpose of response rate estimation. Two hundred forty-one complete responses and 76 partial responses were observed, for an estimated response rate of 94% (95% CI: 91.3%, 96.6%). After two initial cycles of ABVD, 343 patients registered to Step 2 of the study to receive responseadapted therapy, including 285 PET2-negative patients to receive four additional cycles of ABVD and 58 PET2-positive patients to receive six cycles of escalated BEACOPP (ebeacopp). Fifteen PET2- negative patients on the continued ABVD arm and three PET2-positive patients on the ebeacopp arm are ineligible because they were ineligible for the initial registration. Six PET2-positive patients who did not receive ebeacopp are coded as major protocol deviations and not evaluable for adverse events. Two hundred seventy patients on the continued ABVD arm were assessed for toxicity. One patient died due to treatment related pneumonitis. Ninetyeight patients experienced 4 toxicities, primarily hematologic. Of these, six patients experienced the following 4 non-hematologic toxicities: thrombosis/embolism (2 patients), acute respiratory distress syndrome (ARDS), allergic reaction, colitis, dyspnea, and lung infection (coded as "Lung inf, 0-2 ANC: lung") (1 patient each). Ninety-two patients experienced 3 toxicities as maximum degree. Forty-nine patients on the ebeacopp arm were assessed for toxicity. Two patient deaths were found upon central review to be definitely treatment-related: one patient died due to blood infection during the second treatment cycle and had also experienced 4 febrile neutropenia, another patient died due to pneumonitis and had also experienced 4 dyspnea. Forty-one additional patients experienced 4 toxicities, primarily hematologic. Of these, six patients experienced the following 4 nonhematologic toxicities: febrile neutropenia (2 patients), dizziness, hyponatremia, blood infection (coded as "Inf, 3-4 ANC: blood"), oral cavity (coded as "Mucositis, clin: oral cavity"), and sensory neuropathy (1 patient each). Five patients experienced 3 toxicities as maximum degree. Of 325 patients treated with two cycles of ABVD followed by response-adapted therapy, one patient on the ABVD arm and seven patients on the ebeacopp arm who did not have response adequately assessed are assumed non-responders for the purpose of response rate estimation. On the two cycles of ABVD followed by ABVD arm, 258 complete responses and 11 partial responses were observed, for an estimated response rate of 99.6% (95% CI: 97.9%, 100%). On the two cycles of ABVD followed by ebeacopp arm, 30 complete responses and 15 partial responses were observed, for an estimated response rate of 82% (95% CI: 69.1%, 90.9%). The median length of follow-up among HIV-negative patients last known to be alive is 5.4 years (range 2.1 months - 7.7 years). Eighty-four patients have either progressed or died, for an estimated 2-year progression-free survival of 79% (95% CI: 73.9%, 82.8%). There have been 19 deaths, for an estimated 2-year overall survival of 98% (95% CI: 95.2%, 98.8%). HIV-positive cohort: Of 13 HIV-positive patients enrolled, one patient is ineligible due to insufficient baseline documentation. All 12 eligible patients completed two initial cycles of ABVD and were assessed for toxicity during treatment. Eight patients experienced 4 toxicities including neutrophils (8), leukocytes (2), and hyponatremia (1). Two additional patients experienced 3 toxicities as maximum degree. Among 12 patients assessed for response during two initial cycles of ABVD, eight complete responses and four partial responses were observed, for an estimated response rate of 100% (95% CI: 73.5%, 100%). After two initial cycles of ABVD, 12 patients registered to Step 2 of the study to receive responseadapted therapy, including 11 PET2-negative to receive additional four cycles of ABVD and one PET2-positive patient to receive six cycles of standard BEACOPP. One PET2-negative patient is ineligible because the patient was ineligible for the initial registration. Nine out of ten PET2-negative patients completed additional four cycles of ABVD and one PET2-positive patient completed six cycles of standard BEACOPP as planned. One PET2- negative patient discontinued ABVD treatment due to progressive disease. Ten HIV-positive patients on the continued ABVD arm were assessed for toxicity. Six patients experienced the following 4 toxicities: APRIL 11-14, 2018 SWOG LYMPHOMA 8

neutrophils (5), anemia (2), leukocytes (2), and lymphopenia (1). Three additional patients experienced 3 toxicities as maximum degree. One patient on the standard BEACOPP arm experienced 4 leukocyte, lymphopenia, neutrophils and 3 anemia and urine track infection. Of ten HIV-positive patients treated with two initial cycles of ABVD followed by four additional cycles of ABVD, nine complete responses and one partial response were observed, for an estimated response rate of 100% (95% CI: 69.2%, 100%). The one patient treated with two initial cycles of ABVD followed by six cycles of standard BEACOPP achieved partial response. The median length of follow-up among HIV-positive patients last known to be alive is 5.3 years (range 0.5-6.2 years). Four patients have either progressed or died, for an estimated 2-year progression-free survival of 83% (95% CI: 46.1%, 95.3%). There were no patient deaths in the first two years for a 100% estimated 2-year overall survival. Of 12 eligible HIVpositive patients, one patient death occurred at 4.5 years after registration. Initial Registrations By 3 Month Intervals 60 50 50 40 30 20 22 18 25 22 32 30 35 31 38 32 28 10 7 0 1 Jul Sep 2009 Oct Dec 2009 Jan Mar 2010 Apr Jun 2010 Jul Sep 2010 Oct Dec 2010 Jan Mar 2011 Apr Jun 2011 Jul Sep 2011 Oct Dec 2011 Jan Mar 2012 Apr Jun 2012 Jul Sep 2012 Oct Dec 2012 Time of Registration Initial ABVD APRIL 11-14, 2018 SWOG LYMPHOMA 9

Registration by Institution Institutions Total Reg Institutions Rochester, Univ of 18 ECOG-ACRIN 71 MD Anderson CC 16 CTSU 24 Michigan, U of 13 AMC 4 PCRC NCORP 10 NRG 3 All Other SWOG Institutions 98 Total (46 Institutions) 371 ALLIANCE 114 Total Reg HIV-negative Cohort Registration, Eligibility, and Evaluability Initial Registration HIV-negative Patients Initial ABVD NUMBER REGISTERED 358 INELIGIBLE 20 ELIGIBLE 338 Not Analyzable 2 ADVERSE EVENT ASSESSMENT Evaluable 336 APRIL 11-14, 2018 SWOG LYMPHOMA 10

Patient Characteristics Initial Registration HIV-negative Patients Initial ABVD (n=336) AGE Median 32.1 Minimum 18.1 Maximum 60.9 SEX Males 189 56% Females 147 44% HISPANIC Yes 28 8% No 273 81% Unknown 35 10% RACE White 274 82% Black 32 10% Asian 7 2% Pacific Islander 3 1% Multi-Racial 3 1% Unknown 17 5% Treatment Summary Initial Registration HIV-negative Patients Initial ABVD NUMBER ON PROTOCOL TREATMENT 0 NUMBER OFF PROTOCOL TREATMENT 336 REASON OFF TREATMENT Treatment completed as planned 333 Adverse Event or side effects 1 Refusal unrelated to adverse event 1 Progression/relapse 0 Death 0 Other - not protocol specified 1 Reason under review 0 MAJOR PROTOCOL DEVIATIONS 0 APRIL 11-14, 2018 SWOG LYMPHOMA 11

Number of Patients with a Given Type and of Adverse Event Initial Registration HIV-negative Patients Adverse Events Unlikely or Not Related to Treatment Excluded APRIL 11-14, 2018 SWOG LYMPHOMA 12 Initial ABVD (n=336) ADVERSE EVENTS 0 1 2 3 4 5 ALT 278 47 8 3 0 0 AST 293 37 5 1 0 0 Acne 331 4 1 0 0 0 Alkaline phosphatase 311 22 2 1 0 0 Allergic reaction 332 1 1 2 0 0 Alopecia 256 54 26 0 0 0 Anorexia 296 32 7 1 0 0 Arthritis 335 0 0 1 0 0 Ataxia 335 0 1 0 0 0 Atelectasis 335 0 1 0 0 0 Auditory/Ear-other 335 1 0 0 0 0 Bilirubin 335 1 0 0 0 0 Blood-other 335 1 0 0 0 0 Blurred vision 334 1 1 0 0 0 Bronchospasm 335 1 0 0 0 0 Card Inf, 0-2 ANC: vein 335 0 0 1 0 0 Cheilitis 335 0 1 0 0 0 Cognitive disturbance 335 1 0 0 0 0 Colitis, infectious 335 0 0 1 0 0 Constipation 229 81 25 1 0 0 Constitutional Symptoms-other 335 0 1 0 0 0 Cough 318 16 2 0 0 0 Creatinine 329 7 0 0 0 0 Cytokine release syndrome 334 0 1 1 0 0 Dehydration 331 0 4 1 0 0 Dermatology-other 328 7 1 0 0 0 Diabetes 335 0 0 1 0 0 Diarrhea 310 21 5 0 0 0 Diplopia 335 0 1 0 0 0 Distension 335 1 0 0 0 0 Dizziness 310 21 4 1 0 0 Dry mouth 335 1 0 0 0 0 Dry skin 332 4 0 0 0 0 Dysphagia 334 2 0 0 0 0 Dyspnea 295 33 4 4 0 0 Ear Inf, Unk ANC: ext. ear 335 0 1 0 0 0 Ear Inf, Unk ANC: mid. ear 335 0 1 0 0 0 Ear Pain: middle ear 335 1 0 0 0 0 Edema-head and neck 334 1 1 0 0 0 Edema-limb 327 8 1 0 0 0 Endocrine-other 335 0 1 0 0 0 Erectile dysfunction 335 1 0 0 0 0 Erythema multiforme 334 0 2 0 0 0

APRIL 11-14, 2018 SWOG LYMPHOMA 13 Initial ABVD (n=336) ADVERSE EVENTS 0 1 2 3 4 5 Esophagitis 334 1 1 0 0 0 Fatigue 141 144 41 10 0 0 Febrile neutropenia 328 0 0 7 1 0 Fever 320 12 4 0 0 0 Flatulence 333 3 0 0 0 0 Flushing 332 3 1 0 0 0 GI Inf, 0-2 ANC: gums 334 0 2 0 0 0 GI Inf, 0-2 ANC: tooth 335 0 1 0 0 0 GI Inf, 3-4 ANC: gums 335 0 1 0 0 0 GI Inf, 3-4 ANC: tooth 335 0 1 0 0 0 GI Pain: abdomen 314 12 8 1 1 0 GI Pain: anus 335 0 1 0 0 0 GI Pain: dental 335 0 1 0 0 0 GI Pain: oral cavity 323 11 1 1 0 0 GI Pain: stomach 333 1 2 0 0 0 GI-other 330 4 2 0 0 0 GU Hemorrhage: urinary 334 2 0 0 0 0 GU Inf, 0-2 ANC: bladder 335 0 1 0 0 0 GU Inf, 3-4 ANC: UTI 335 0 1 0 0 0 GU Pain: bladder 335 1 0 0 0 0 Gastritis 333 2 1 0 0 0 Hand-foot 334 1 1 0 0 0 Heartburn 311 13 11 1 0 0 Hemoglobin 184 113 29 9 1 0 Hemorrhage-other 335 1 0 0 0 0 Hemorrhoids 334 1 1 0 0 0 Hiccoughs 327 7 2 0 0 0 Hot flashes 331 4 1 0 0 0 Hypercalcemia 333 3 0 0 0 0 Hyperglycemia 292 38 6 0 0 0 Hyperkalemia 334 2 0 0 0 0 Hypermagnesemia 335 1 0 0 0 0 Hypernatremia 334 2 0 0 0 0 Hyperpigmentation 325 11 0 0 0 0 Hypertension 334 2 0 0 0 0 Hyperuricemia 335 1 0 0 0 0 Hypoalbuminemia 313 18 4 1 0 0 Hypocalcemia 316 17 3 0 0 0 Hypoglycemia 331 4 1 0 0 0 Hypokalemia 331 5 0 0 0 0 Hypomagnesemia 331 4 1 0 0 0 Hyponatremia 326 9 0 1 0 0 Hypophosphatemia 335 0 0 1 0 0 Hypotension 334 1 1 0 0 0 Ileus 334 0 2 0 0 0 Inf, 0-2 ANC: cath.-related 335 0 0 1 0 0 Inf, 3-4 ANC: blood 334 0 0 0 2 0 Infection-other 330 3 3 0 0 0 Injection site reaction 324 7 5 0 0 0 Insomnia 305 21 10 0 0 0 Involuntary movement 334 1 1 0 0 0

APRIL 11-14, 2018 SWOG LYMPHOMA 14 Initial ABVD (n=336) ADVERSE EVENTS 0 1 2 3 4 5 Irregular menses 335 1 0 0 0 0 Left vent. diastolic dysfunct. 335 1 0 0 0 0 Left vent. systolic dysfunct. 335 1 0 0 0 0 Leukocytes 125 42 96 59 14 0 Lung Hemorrhage: nose 335 1 0 0 0 0 Lung Inf, 0-2 ANC: lung 335 0 0 1 0 0 Lung Inf, 0-2 ANC: mucosa 335 0 1 0 0 0 Lung Inf, 0-2 ANC: sinus 335 0 1 0 0 0 Lung Inf, 0-2 ANC: up. airway 335 0 1 0 0 0 Lung Inf, 3-4 ANC: mucosa 335 0 0 0 1 0 Lung Inf, 3-4 ANC: pharynx 334 0 2 0 0 0 Lung Inf, 3-4 ANC: sinus 335 0 1 0 0 0 Lung Inf, 3-4 ANC: up. aero. 335 0 1 0 0 0 Lung Inf, 3-4 ANC: up. airway 334 0 2 0 0 0 Lung Inf, Unk ANC: sinus 335 0 1 0 0 0 Lung Pain: chest wall 333 2 0 0 1 0 Lung Pain: chest/thorax 328 6 2 0 0 0 Lung Pain: larynx 335 1 0 0 0 0 Lung Pain: throat/phar/lar 323 7 6 0 0 0 Lymphatic Pain: lymph node 334 1 1 0 0 0 Lymphopenia 263 28 30 10 5 0 Memory impairment 332 3 1 0 0 0 Metabolic/Lab-other 328 7 0 1 0 0 Mood alteration: agitation 334 1 0 0 1 0 Mood alteration: anxiety 327 6 2 1 0 0 Mood alteration: depression 331 3 1 0 1 0 Mucositis, clin: oral cavity 303 26 6 1 0 0 Mucositis, clin: pharynx 334 2 0 0 0 0 Mucositis, funct: oral cav. 310 17 8 1 0 0 Mucositis, funct: pharynx 335 1 0 0 0 0 Muscle weakness: whole body 333 2 1 0 0 0 Musculo. Pain: back 327 4 4 1 0 0 Musculo. Pain: bone 324 6 6 0 0 0 Musculo. Pain: buttock 335 1 0 0 0 0 Musculo. Pain: joint 311 14 10 1 0 0 Musculo. Pain: limb 322 9 4 1 0 0 Musculo. Pain: muscle 304 19 12 1 0 0 Musculo. Pain: neck 334 1 1 0 0 0 Musculoskeletal-other 332 4 0 0 0 0 Nail changes 328 7 1 0 0 0 Nasal/paranasal reactions 335 1 0 0 0 0 Nausea 136 150 43 6 1 0 Neuro Inf, 3-4 ANC: mening. 335 0 0 1 0 0 Neuro Pain: head/headache 304 21 9 2 0 0 Neurology-other 335 1 0 0 0 0 Neuropathy-motor 328 4 2 2 0 0 Neuropathy-sensory 258 62 12 4 0 0 Neutrophils 86 10 34 77 129 0 Ocular-other 328 8 0 0 0 0 PTT 335 1 0 0 0 0 Pain-other 318 12 5 1 0 0

Initial ABVD (n=336) ADVERSE EVENTS 0 1 2 3 4 5 Pain: NOS 334 1 1 0 0 0 Pain: tumor pain 335 0 0 1 0 0 Palpitations 335 0 1 0 0 0 Periodontal 335 1 0 0 0 0 Phlebitis 332 0 4 0 0 0 Platelets 320 13 2 1 0 0 Pneumonitis 334 0 1 1 0 0 Pruritus 325 9 2 0 0 0 Pulmonary-other 335 1 0 0 0 0 Rash 302 21 12 1 0 0 Renal-other 334 0 2 0 0 0 Rhinitis 331 5 0 0 0 0 Rigors/chills 320 13 2 1 0 0 Salivary gland changes 335 0 1 0 0 0 Sex/Rep Inf, 3-4 ANC: vagina 335 0 0 1 0 0 Sexual/Repro. Pain: vagina 335 1 0 0 0 0 Skin Inf, 0-2 ANC: skin 333 0 2 1 0 0 Skin Inf, 3-4 ANC: lip/perior. 335 0 1 0 0 0 Skin Inf, 3-4 ANC: skin 335 0 1 0 0 0 Skin Pain: gums 335 1 0 0 0 0 Supra Arrhyth: Atrial Tachy. 335 1 0 0 0 0 Supra Arrhyth: Sinus Tachy. 333 2 1 0 0 0 Sweating 323 12 1 0 0 0 Syncope 335 0 0 1 0 0 Taste alteration 298 33 5 0 0 0 Thrombosis/embolism 332 0 2 2 0 0 Thrombosis/embolism (vasc acc) 335 0 1 0 0 0 Trismus 334 2 0 0 0 0 Ulceration 334 0 2 0 0 0 Urinary frequency 333 2 1 0 0 0 Vaginal discharge 335 1 0 0 0 0 Vascular-other 335 1 0 0 0 0 Voice changes 335 1 0 0 0 0 Vomiting 269 45 17 5 0 0 Watery eye 335 1 0 0 0 0 Weight Loss 329 5 2 0 0 0 Weight gain 329 7 0 0 0 0 MAX. GRADE ANY ADVERSE EVENT 3 41 64 92 136 0 APRIL 11-14, 2018 SWOG LYMPHOMA 15

Response Initial Registration HIV-negative Patients Initial ABVD N % Complete Response 241 72 Partial Response 76 23 Stable/No Response 11 3 Assessment Inadequate 8 2 Total 336 100 Registration, Eligibility, and Evaluability Continued Therapy HIV-negative Patients TOTAL Continued ABVD BEACOPP NUMBER REGISTERED 343 285 58 INELIGIBLE 18 15 3 ELIGIBLE 325 270 55 ADVERSE EVENT ASSESSMENT Evaluable 319 270 49 Not Evaluable 6 0 6 Treatment Summary Continued Therapy HIV-negative Patients TOTAL Continued ABVD BEACOPP NUMBER ON PROTOCOL TREATMENT 0 0 0 NUMBER OFF PROTOCOL TREATMENT 325 270 55 REASON OFF TREATMENT Treatment completed as planned 309 261 48 Adverse Event or side effects 6 5 1 Refusal unrelated to adverse event 6 2 4 Progression/relapse 1 1 0 Death 2 0 2 Other - not protocol specified 1 1 0 Reason under review 0 0 0 MAJOR PROTOCOL DEVIATIONS 6 0 6 APRIL 11-14, 2018 SWOG LYMPHOMA 16

Number of Patients with a Given Type and of Adverse Event Continued Therapy HIV-negative Patients Adverse Events Unlikely or Not Related to Treatment Excluded Continued ABVD (n=270) APRIL 11-14, 2018 SWOG LYMPHOMA 17 BEACOPP (n=49) ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5 ALT 228 38 4 0 0 0 36 10 3 0 0 0 ARDS 268 0 0 1 1 0 49 0 0 0 0 0 AST 238 29 3 0 0 0 40 8 1 0 0 0 Acne 263 4 3 0 0 0 47 0 2 0 0 0 Alkaline phosphatase 261 9 0 0 0 0 44 5 0 0 0 0 Allergic reaction 265 3 0 1 1 0 45 4 0 0 0 0 Alopecia 174 57 39 0 0 0 33 5 11 0 0 0 Anorexia 223 36 10 1 0 0 36 9 4 0 0 0 Ataxia 267 2 1 0 0 0 49 0 0 0 0 0 Auditory/Ear-other 270 0 0 0 0 0 48 0 1 0 0 0 Bilirubin 267 2 1 0 0 0 47 2 0 0 0 0 Blood-other 269 1 0 0 0 0 49 0 0 0 0 0 Blurred vision 265 3 2 0 0 0 47 2 0 0 0 0 Bronchospasm 266 4 0 0 0 0 47 0 2 0 0 0 Cardiac Arrhythmia-other 270 0 0 0 0 0 48 1 0 0 0 0 Cardio. Pain: cardiac/heart 269 0 0 1 0 0 48 0 1 0 0 0 Chest tube drainage or leak 269 0 1 0 0 0 49 0 0 0 0 0 Cognitive disturbance 269 1 0 0 0 0 48 1 0 0 0 0 Colitis 269 0 0 0 1 0 49 0 0 0 0 0 Colitis, infectious 270 0 0 0 0 0 48 0 0 1 0 0 Constipation 201 52 17 0 0 0 40 5 4 0 0 0 Constitutional Symptoms-other 269 1 0 0 0 0 49 0 0 0 0 0 Cough 227 26 16 1 0 0 39 9 1 0 0 0 Creatinine 264 6 0 0 0 0 44 3 1 1 0 0 Cushingoid 270 0 0 0 0 0 48 0 1 0 0 0 Cystitis 270 0 0 0 0 0 47 2 0 0 0 0 DLCO 263 1 4 2 0 0 49 0 0 0 0 0 Dehydration 261 0 7 2 0 0 45 1 2 1 0 0 Dermatology-other 259 10 1 0 0 0 47 1 1 0 0 0 Diabetes 269 0 0 1 0 0 49 0 0 0 0 0 Diarrhea 237 27 5 1 0 0 35 10 4 0 0 0 Diplopia 269 0 1 0 0 0 49 0 0 0 0 0 Distension 266 1 3 0 0 0 49 0 0 0 0 0 Dizziness 248 19 3 0 0 0 38 8 2 0 1 0 Dry eye 267 2 1 0 0 0 49 0 0 0 0 0 Dry mouth 269 1 0 0 0 0 48 1 0 0 0 0 Dry skin 261 8 1 0 0 0 48 1 0 0 0 0 Dysphagia 268 2 0 0 0 0 46 2 1 0 0 0 Dyspnea 210 38 13 8 1 0 34 10 4 0 1 0 Ear Inf, 0-2 ANC: mid. ear 270 0 0 0 0 0 48 0 1 0 0 0 Ear Pain: external ear 269 1 0 0 0 0 49 0 0 0 0 0 Ear Pain: middle ear 269 1 0 0 0 0 49 0 0 0 0 0 Edema-head and neck 270 0 0 0 0 0 48 1 0 0 0 0

Continued ABVD (n=270) APRIL 11-14, 2018 SWOG LYMPHOMA 18 BEACOPP (n=49) ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5 Edema-limb 254 16 0 0 0 0 38 11 0 0 0 0 Endocrine-other 270 0 0 0 0 0 48 1 0 0 0 0 Erectile dysfunction 268 1 1 0 0 0 49 0 0 0 0 0 Erythema multiforme 269 0 1 0 0 0 49 0 0 0 0 0 Esophagitis 269 1 0 0 0 0 49 0 0 0 0 0 Eye Inf, 3-4 ANC: conjunct. 269 0 1 0 0 0 49 0 0 0 0 0 Eye Pain: eye 269 1 0 0 0 0 49 0 0 0 0 0 FEV1 268 0 1 1 0 0 49 0 0 0 0 0 Fatigue 84 101 70 15 0 0 13 15 18 3 0 0 Febrile neutropenia 253 0 0 17 0 0 32 0 0 14 3 0 Fever 244 18 5 3 0 0 42 4 2 1 0 0 Flatulence 266 2 2 0 0 0 47 1 1 0 0 0 Flu-like syndrome 270 0 0 0 0 0 48 1 0 0 0 0 GI Hemorrhage: rectum 267 3 0 0 0 0 49 0 0 0 0 0 GI Inf, 0-2 ANC: gums 270 0 0 0 0 0 47 0 1 1 0 0 GI Inf, 0-2 ANC: stomach 269 0 1 0 0 0 49 0 0 0 0 0 GI Inf, 0-2 ANC: tooth 270 0 0 0 0 0 48 0 1 0 0 0 GI Inf, 3-4 ANC: anal/perian. 269 0 1 0 0 0 49 0 0 0 0 0 GI Inf, 3-4 ANC: colon 270 0 0 0 0 0 48 0 0 1 0 0 GI Inf, 3-4 ANC: gums 270 0 0 0 0 0 47 0 2 0 0 0 GI Inf, 3-4 ANC: stomach 269 0 1 0 0 0 49 0 0 0 0 0 GI Inf, Unk ANC: gums 270 0 0 0 0 0 48 0 1 0 0 0 GI Pain: abdomen 251 9 5 5 0 0 45 3 0 1 0 0 GI Pain: dental 269 1 0 0 0 0 47 0 2 0 0 0 GI Pain: esophagus 269 1 0 0 0 0 48 0 1 0 0 0 GI Pain: oral cavity 266 4 0 0 0 0 45 2 2 0 0 0 GI Pain: rectum 270 0 0 0 0 0 48 0 1 0 0 0 GI Pain: stomach 267 1 1 1 0 0 49 0 0 0 0 0 GI Ulcer: stomach 269 0 1 0 0 0 49 0 0 0 0 0 GI-other 265 4 1 0 0 0 49 0 0 0 0 0 GU Hemorrhage: urinary 270 0 0 0 0 0 48 1 0 0 0 0 GU Hemorrhage: vagina 270 0 0 0 0 0 48 1 0 0 0 0 GU Inf, 0-2 ANC: UTI 269 0 1 0 0 0 49 0 0 0 0 0 GU Inf, 0-2 ANC: bladder 269 0 1 0 0 0 49 0 0 0 0 0 GU Inf, 3-4 ANC: UTI 269 0 0 1 0 0 48 0 0 1 0 0 GU Inf, Unk ANC: UTI 269 0 1 0 0 0 49 0 0 0 0 0 GU Pain: bladder 269 1 0 0 0 0 49 0 0 0 0 0 Gastritis 269 0 1 0 0 0 49 0 0 0 0 0 Hand-foot 269 1 0 0 0 0 49 0 0 0 0 0 Hearing (w/o monit. prog.) 269 0 1 0 0 0 49 0 0 0 0 0 Heartburn 244 21 5 0 0 0 47 1 1 0 0 0 Hemoglobin 117 120 29 4 0 0 5 1 6 33 4 0 Hemolysis 270 0 0 0 0 0 48 0 0 1 0 0 Hemorrhoids 266 2 2 0 0 0 48 1 0 0 0 0 Hiccoughs 265 3 2 0 0 0 48 0 1 0 0 0 Hot flashes 256 10 4 0 0 0 43 5 1 0 0 0 Hypercalcemia 267 3 0 0 0 0 48 1 0 0 0 0 Hyperglycemia 218 48 3 1 0 0 35 11 2 1 0 0 Hyperkalemia 266 4 0 0 0 0 45 3 0 1 0 0 Hypernatremia 268 2 0 0 0 0 48 1 0 0 0 0 Hyperpigmentation 253 16 1 0 0 0 47 2 0 0 0 0

Continued ABVD (n=270) APRIL 11-14, 2018 SWOG LYMPHOMA 19 BEACOPP (n=49) ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5 Hypertension 265 3 2 0 0 0 48 1 0 0 0 0 Hypertriglyceridemia 269 1 0 0 0 0 49 0 0 0 0 0 Hyperuricemia 270 0 0 0 0 0 45 4 0 0 0 0 Hypoalbuminemia 244 25 1 0 0 0 37 10 2 0 0 0 Hypocalcemia 249 21 0 0 0 0 36 9 4 0 0 0 Hypoglycemia 268 2 0 0 0 0 46 2 1 0 0 0 Hypokalemia 257 13 0 0 0 0 29 16 0 4 0 0 Hypomagnesemia 269 1 0 0 0 0 45 4 0 0 0 0 Hyponatremia 256 14 0 0 0 0 41 7 0 0 1 0 Hypophosphatemia 266 3 1 0 0 0 45 3 1 0 0 0 Hypopigmentation 268 2 0 0 0 0 48 1 0 0 0 0 Hypotension 266 0 4 0 0 0 47 0 1 1 0 0 Hypoxia 266 0 1 3 0 0 48 0 0 1 0 0 Incontinence, urinary 269 1 0 0 0 0 49 0 0 0 0 0 Induration 269 1 0 0 0 0 49 0 0 0 0 0 Inf, 3-4 ANC: blood 269 0 0 1 0 0 47 0 0 0 1 1 Infection-other 263 3 4 0 0 0 47 1 1 0 0 0 Injection site reaction 259 8 3 0 0 0 47 2 0 0 0 0 Insomnia 236 25 9 0 0 0 39 4 6 0 0 0 Irregular menses 267 3 0 0 0 0 48 0 1 0 0 0 Irritability 269 1 0 0 0 0 49 0 0 0 0 0 Joint-function 269 1 0 0 0 0 48 0 1 0 0 0 Left vent. diastolic dysfunct. 270 0 0 0 0 0 48 1 0 0 0 0 Left vent. systolic dysfunct. 267 1 1 1 0 0 48 0 1 0 0 0 Leukocytes 83 36 65 78 8 0 4 1 2 7 35 0 Lung Hemorrhage: lung 269 0 1 0 0 0 49 0 0 0 0 0 Lung Hemorrhage: nose 268 2 0 0 0 0 45 3 0 1 0 0 Lung Inf, 0-2 ANC: lung 265 0 2 2 1 0 49 0 0 0 0 0 Lung Inf, 0-2 ANC: mucosa 270 0 0 0 0 0 48 0 1 0 0 0 Lung Inf, 0-2 ANC: sinus 269 0 1 0 0 0 48 0 1 0 0 0 Lung Inf, 0-2 ANC: up. airway 267 0 3 0 0 0 48 0 1 0 0 0 Lung Inf, 3-4 ANC: lung 266 0 0 4 0 0 46 0 1 2 0 0 Lung Inf, 3-4 ANC: mucosa 269 0 1 0 0 0 48 0 1 0 0 0 Lung Inf, 3-4 ANC: pharynx 269 0 1 0 0 0 49 0 0 0 0 0 Lung Inf, 3-4 ANC: sinus 267 0 3 0 0 0 49 0 0 0 0 0 Lung Inf, 3-4 ANC: up. aero. 269 0 1 0 0 0 49 0 0 0 0 0 Lung Inf, 3-4 ANC: up. airway 266 0 3 1 0 0 48 0 0 1 0 0 Lung Inf, Unk ANC: bronchus 269 0 1 0 0 0 49 0 0 0 0 0 Lung Inf, Unk ANC: lung 268 0 1 1 0 0 49 0 0 0 0 0 Lung Inf, Unk ANC: nose 270 0 0 0 0 0 48 0 1 0 0 0 Lung Inf, Unk ANC: sinus 269 0 1 0 0 0 48 0 1 0 0 0 Lung Inf, Unk ANC: up. airway 270 0 0 0 0 0 48 0 1 0 0 0 Lung Pain: chest wall 265 3 1 1 0 0 46 1 2 0 0 0 Lung Pain: chest/thorax 262 4 3 1 0 0 45 2 1 1 0 0 Lung Pain: sinus 269 1 0 0 0 0 48 1 0 0 0 0 Lung Pain: throat/phar/lar 260 10 0 0 0 0 45 2 1 1 0 0 Lymphatics-other 269 1 0 0 0 0 49 0 0 0 0 0 Lymphopenia 178 31 31 29 1 0 17 0 0 11 21 0 Memory impairment 262 6 2 0 0 0 48 1 0 0 0 0 Metabolic/Lab-other 267 3 0 0 0 0 45 3 1 0 0 0 Mood alteration: agitation 270 0 0 0 0 0 48 1 0 0 0 0

Continued ABVD (n=270) APRIL 11-14, 2018 SWOG LYMPHOMA 20 BEACOPP (n=49) ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5 Mood alteration: anxiety 259 6 5 0 0 0 44 3 2 0 0 0 Mood alteration: depression 266 3 1 0 0 0 48 1 0 0 0 0 Mucositis, clin: oral cavity 246 16 8 0 0 0 36 5 6 1 1 0 Mucositis, clin: pharynx 269 1 0 0 0 0 49 0 0 0 0 0 Mucositis, funct: esophagus 270 0 0 0 0 0 48 1 0 0 0 0 Mucositis, funct: oral cav. 258 8 4 0 0 0 47 0 1 1 0 0 Mucositis, funct: pharynx 267 3 0 0 0 0 49 0 0 0 0 0 Musc Inf, 3-4 ANC: soft tissue 269 0 0 1 0 0 49 0 0 0 0 0 Musc Inf, Unk ANC: soft tiss. 270 0 0 0 0 0 48 0 1 0 0 0 Muscle weakness: extraocular 270 0 0 0 0 0 48 1 0 0 0 0 Muscle weakness: low. extrem. 267 3 0 0 0 0 48 1 0 0 0 0 Muscle weakness: up. extrem. 268 2 0 0 0 0 49 0 0 0 0 0 Muscle weakness: whole body 263 5 2 0 0 0 43 2 3 1 0 0 Musculo. Pain: back 264 1 5 0 0 0 42 2 2 3 0 0 Musculo. Pain: bone 258 4 8 0 0 0 31 4 9 5 0 0 Musculo. Pain: joint 248 9 13 0 0 0 38 6 4 1 0 0 Musculo. Pain: limb 258 9 3 0 0 0 45 2 2 0 0 0 Musculo. Pain: muscle 234 24 11 1 0 0 41 5 3 0 0 0 Musculo. Pain: neck 268 1 1 0 0 0 48 0 1 0 0 0 Musculoskeletal-other 264 3 2 1 0 0 48 1 0 0 0 0 Nail changes 241 24 5 0 0 0 45 2 2 0 0 0 Nasal/paranasal reactions 266 4 0 0 0 0 49 0 0 0 0 0 Nausea 100 117 48 5 0 0 20 15 12 2 0 0 Neuro Pain: head/headache 241 19 8 2 0 0 37 7 5 0 0 0 Neurology-other 268 2 0 0 0 0 48 0 1 0 0 0 Neurop: smell 269 0 1 0 0 0 49 0 0 0 0 0 Neuropathy-motor 258 7 2 3 0 0 48 0 1 0 0 0 Neuropathy-sensory 171 73 14 12 0 0 18 15 12 3 1 0 Neutrophils 58 13 34 71 94 0 8 1 2 4 34 0 Ocular-other 260 10 0 0 0 0 47 2 0 0 0 0 Opportunistic infection 270 0 0 0 0 0 48 0 1 0 0 0 Osteonecrosis 270 0 0 0 0 0 48 0 0 1 0 0 PTT 270 0 0 0 0 0 48 0 1 0 0 0 Pain-other 248 12 8 2 0 0 43 4 2 0 0 0 Pain: NOS 269 1 0 0 0 0 48 0 1 0 0 0 Pain: tumor pain 269 0 1 0 0 0 49 0 0 0 0 0 Palpitations 267 2 1 0 0 0 49 0 0 0 0 0 Petechiae 270 0 0 0 0 0 48 1 0 0 0 0 Phlebitis 262 0 8 0 0 0 47 0 2 0 0 0 Photophobia 269 1 0 0 0 0 49 0 0 0 0 0 Photosensitivity 269 1 0 0 0 0 49 0 0 0 0 0 Platelets 248 21 1 0 0 0 5 5 5 13 21 0 Pleural effusion 269 0 1 0 0 0 49 0 0 0 0 0 Pneumonitis 258 6 2 3 0 1 45 1 2 0 0 1 Proteinuria 268 2 0 0 0 0 48 1 0 0 0 0 Pruritus 256 12 2 0 0 0 48 1 0 0 0 0 Pulmonary fibrosis 267 0 3 0 0 0 49 0 0 0 0 0 Pulmonary-other 260 5 5 0 0 0 48 0 1 0 0 0 Rash 231 28 11 0 0 0 42 4 3 0 0 0 Renal-other 269 1 0 0 0 0 48 1 0 0 0 0 Rhinitis 256 12 2 0 0 0 49 0 0 0 0 0

Continued ABVD (n=270) BEACOPP (n=49) ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5 Rigors/chills 255 9 6 0 0 0 39 5 3 2 0 0 Salivary gland changes 269 0 1 0 0 0 49 0 0 0 0 0 Sex/Rep Inf, 0-2 ANC: vagina 269 0 1 0 0 0 48 0 1 0 0 0 Sex/Rep Inf, 3-4 ANC: vagina 270 0 0 0 0 0 48 0 1 0 0 0 Sexual-other 269 0 1 0 0 0 49 0 0 0 0 0 Skin Inf, 0-2 ANC: skin 269 0 1 0 0 0 47 0 1 1 0 0 Skin Inf, 3-4 ANC: lip/perior. 270 0 0 0 0 0 48 0 1 0 0 0 Skin Inf, 3-4 ANC: skin 266 0 3 1 0 0 46 0 0 3 0 0 Skin Inf, 3-4 ANC: ungual 269 0 1 0 0 0 49 0 0 0 0 0 Skin Inf, Unk ANC: skin 269 0 1 0 0 0 49 0 0 0 0 0 Skin Pain: face 269 1 0 0 0 0 49 0 0 0 0 0 Skin Pain: gums 269 1 0 0 0 0 49 0 0 0 0 0 Skin Pain: scalp 268 2 0 0 0 0 49 0 0 0 0 0 Skin Pain: skin 269 0 0 1 0 0 49 0 0 0 0 0 Supra Arrhyth: NOS 270 0 0 0 0 0 48 0 1 0 0 0 Supra Arrhyth: Sinus Tachy. 265 4 1 0 0 0 46 3 0 0 0 0 Sweating 247 18 5 0 0 0 41 4 4 0 0 0 Syncope 270 0 0 0 0 0 48 0 0 1 0 0 Taste alteration 236 25 9 0 0 0 42 5 2 0 0 0 Thrombosis/embolism 263 0 2 3 2 0 48 0 1 0 0 0 Tinnitus 270 0 0 0 0 0 48 0 1 0 0 0 Tremor 268 2 0 0 0 0 49 0 0 0 0 0 Ulceration 270 0 0 0 0 0 48 0 1 0 0 0 Urinary frequency 268 1 1 0 0 0 47 2 0 0 0 0 Vaginal discharge 269 0 1 0 0 0 49 0 0 0 0 0 Vent Arrhyth: Vent Tachy. 269 1 0 0 0 0 49 0 0 0 0 0 Vital capacity 269 0 1 0 0 0 49 0 0 0 0 0 Voice changes 270 0 0 0 0 0 46 3 0 0 0 0 Vomiting 198 47 21 4 0 0 30 9 10 0 0 0 Watery eye 267 3 0 0 0 0 49 0 0 0 0 0 Weight Loss 260 7 3 0 0 0 48 0 1 0 0 0 Weight gain 255 9 4 2 0 0 47 1 1 0 0 0 MAX. GRADE ANY ADVERSE EVENT 3 19 57 92 98 1 0 0 1 5 41 2 Response Two Initial Cycles of ABVD Followed by Response-adapted Therapy HIV-negative Patients Continued ABVD BEACOPP N % N % Complete Response 258 96 30 55 Partial Response 11 4 15 27 Stable/No Response 0 0 3 5 Assessment Inadequate 1 0 7 13 Total 270 100 55 100 APRIL 11-14, 2018 SWOG LYMPHOMA 21

100% Progression-Free Survival HIV-negative Patients 80% 60% 40% 20% 0% At Risk 336 Failed 84 2-Year Estimate 79% At Risk At Risk 336 282 255 231 213 155 0 12 24 36 48 60 Months After Registration Stratum The LIFETEST 1: rowno = Procedure Initial ABVD Overall Survival HIV-negative Patients 100% 80% 60% 40% 20% 0% At Risk 336 Deaths 19 2-Year Estimate 98% At Risk At Risk 336 324 316 288 265 198 0 12 24 36 48 60 Months After Registration APRIL 11-14, 2018 SWOG LYMPHOMA 22

HIV-positive Cohort Registration, Eligibility, and Evaluability Initial Registration HIV-positive Patients Initial ABVD NUMBER REGISTERED 13 INELIGIBLE 1 ELIGIBLE 12 ADVERSE EVENT ASSESSMENT Evaluable 12 Patient Characteristics Initial Registration HIV-positive Patients Initial ABVD (n=12) AGE Median 44.6 Minimum 25.2 Maximum 50.3 SEX Males 10 83% Females 2 17% HISPANIC Yes 3 25% No 8 67% Unknown 1 8% RACE White 5 42% Black 4 33% Unknown 3 25% APRIL 11-14, 2018 SWOG LYMPHOMA 23

Treatment Summary Initial Registration HIV-positive Patients Initial ABVD NUMBER ON PROTOCOL TREATMENT 0 NUMBER OFF PROTOCOL TREATMENT 12 REASON OFF TREATMENT Treatment completed as planned 12 Adverse Event or side effects 0 Refusal unrelated to adverse event 0 Progression/relapse 0 Death 0 Other - not protocol specified 0 Reason under review 0 MAJOR PROTOCOL DEVIATIONS 0 Number of Patients with a Given Type and of Adverse Event Initial Registration HIV-positive Patients Adverse Events Unlikely or Not Related to Treatment Excluded Initial ABVD (n=12) ADVERSE EVENTS 0 1 2 3 4 5 Alkaline phosphatase 10 2 0 0 0 0 Alopecia 10 0 2 0 0 0 Anorexia 9 1 2 0 0 0 Colitis, infectious 11 0 1 0 0 0 Confusion 11 1 0 0 0 0 Constipation 8 3 1 0 0 0 Creatinine 10 2 0 0 0 0 Cytokine release syndrome 11 0 1 0 0 0 Dehydration 11 0 1 0 0 0 Diarrhea 9 2 1 0 0 0 Dizziness 10 1 1 0 0 0 Dyspnea 11 0 1 0 0 0 Eye Inf, 3-4 ANC: eye 11 0 0 1 0 0 Fatigue 7 3 1 1 0 0 Febrile neutropenia 9 0 0 3 0 0 Fever 11 0 1 0 0 0 GI Pain: abdomen 11 0 1 0 0 0 Gastritis 11 0 1 0 0 0 Hemoglobin 7 2 2 1 0 0 Hot flashes 11 1 0 0 0 0 Hyperglycemia 10 2 0 0 0 0 APRIL 11-14, 2018 SWOG LYMPHOMA 24

Initial ABVD (n=12) ADVERSE EVENTS 0 1 2 3 4 5 Hypertension 11 1 0 0 0 0 Hypocalcemia 11 0 1 0 0 0 Hypoglycemia 11 1 0 0 0 0 Hypokalemia 11 1 0 0 0 0 Hyponatremia 11 0 0 0 1 0 Hypophosphatemia 11 0 0 1 0 0 Hypotension 11 1 0 0 0 0 Insomnia 11 0 0 1 0 0 Leukocytes 4 0 1 5 2 0 Libido 11 0 1 0 0 0 Lymphopenia 8 1 2 1 0 0 Mood alteration: agitation 11 0 0 1 0 0 Mood alteration: anxiety 11 0 0 1 0 0 Mucositis, clin: oral cavity 10 1 1 0 0 0 Mucositis, funct: oral cav. 11 0 1 0 0 0 Muscle weakness: whole body 10 0 1 1 0 0 Musculo. Pain: back 11 0 1 0 0 0 Musculo. Pain: bone 10 1 0 1 0 0 Musculo. Pain: joint 10 1 0 1 0 0 Musculo. Pain: muscle 11 0 1 0 0 0 Nail changes 11 1 0 0 0 0 Nausea 8 3 1 0 0 0 Neuro Pain: head/headache 8 3 1 0 0 0 Neuropathy-motor 11 1 0 0 0 0 Neuropathy-sensory 6 4 1 1 0 0 Neutrophils 3 1 0 0 8 0 Phlebitis 11 0 1 0 0 0 Platelets 10 2 0 0 0 0 Pruritus 10 1 1 0 0 0 Rash 11 1 0 0 0 0 Rigors/chills 10 1 1 0 0 0 Supra Arrhyth: Sinus Tachy. 11 1 0 0 0 0 Sweating 11 1 0 0 0 0 Urinary frequency 11 0 1 0 0 0 Vomiting 9 2 1 0 0 0 Weight Loss 11 1 0 0 0 0 MAX. GRADE ANY ADVERSE EVENT 0 0 2 2 8 0 Response Initial Registration HIV-positive Patients Initial ABVD N % Complete Response 8 67 Partial Response 4 33 Total 12 100 APRIL 11-14, 2018 SWOG LYMPHOMA 25

Registration, Eligibility, and Evaluability Continued Therapy HIV-positive Patients TOTAL Continued ABVD BEACOPP NUMBER REGISTERED 12 11 1 INELIGIBLE 1 1 0 ELIGIBLE 11 10 1 ADVERSE EVENT ASSESSMENT Evaluable 11 10 1 Treatment Summary Continued Therapy HIV-positive Patients TOTAL Continued ABVD BEACOPP NUMBER ON PROTOCOL TREATMENT 0 0 0 NUMBER OFF PROTOCOL TREATMENT 11 10 1 REASON OFF TREATMENT Treatment completed as planned 10 9 1 Adverse Event or side effects 0 0 0 Refusal unrelated to adverse event 0 0 0 Progression/relapse 1 1 0 Death 0 0 0 Other - not protocol specified 0 0 0 Reason under review 0 0 0 MAJOR PROTOCOL DEVIATIONS 0 0 0 APRIL 11-14, 2018 SWOG LYMPHOMA 26

Number of Patients with a Given Type and of Adverse Event Continued Therapy HIV-positive Patients Adverse Events Unlikely or Not Related to Treatment Excluded Continued ABVD (n=10) APRIL 11-14, 2018 SWOG LYMPHOMA 27 BEACOPP (n=1) ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5 ALT 8 2 0 0 0 0 1 0 0 0 0 0 AST 7 3 0 0 0 0 1 0 0 0 0 0 Alkaline phosphatase 7 3 0 0 0 0 1 0 0 0 0 0 Alopecia 7 1 2 0 0 0 0 0 1 0 0 0 Anorexia 7 2 0 1 0 0 1 0 0 0 0 0 Bicarbonate, serum-low 9 1 0 0 0 0 1 0 0 0 0 0 CD4 count 9 0 1 0 0 0 1 0 0 0 0 0 Constipation 8 1 1 0 0 0 1 0 0 0 0 0 Cough 7 2 1 0 0 0 1 0 0 0 0 0 Creatinine 8 2 0 0 0 0 0 1 0 0 0 0 DLCO 9 1 0 0 0 0 1 0 0 0 0 0 Diarrhea 5 4 1 0 0 0 1 0 0 0 0 0 Dizziness 9 0 0 1 0 0 1 0 0 0 0 0 Dyspnea 8 1 1 0 0 0 1 0 0 0 0 0 Fatigue 3 3 3 1 0 0 0 1 0 0 0 0 Febrile neutropenia 7 0 0 3 0 0 1 0 0 0 0 0 Fever 7 2 1 0 0 0 0 0 1 0 0 0 GI Pain: abdomen 9 1 0 0 0 0 1 0 0 0 0 0 GI Pain: oral cavity 9 0 1 0 0 0 1 0 0 0 0 0 GU Inf, Unk ANC: UTI 10 0 0 0 0 0 0 0 0 1 0 0 Heartburn 9 1 0 0 0 0 1 0 0 0 0 0 Hemoglobin 3 2 2 1 2 0 0 0 0 1 0 0 Hot flashes 9 1 0 0 0 0 1 0 0 0 0 0 Hyperglycemia 6 4 0 0 0 0 1 0 0 0 0 0 Hypertension 9 1 0 0 0 0 1 0 0 0 0 0 Hypoalbuminemia 9 0 1 0 0 0 1 0 0 0 0 0 Hypocalcemia 7 2 1 0 0 0 0 1 0 0 0 0 Hypokalemia 7 3 0 0 0 0 1 0 0 0 0 0 Hypomagnesemia 9 1 0 0 0 0 1 0 0 0 0 0 Hyponatremia 8 2 0 0 0 0 1 0 0 0 0 0 Hypophosphatemia 9 0 0 1 0 0 1 0 0 0 0 0 Hypotension 9 1 0 0 0 0 1 0 0 0 0 0 Leukocytes 4 0 0 4 2 0 0 0 0 0 1 0 Libido 9 1 0 0 0 0 1 0 0 0 0 0 Lung Inf, 3-4 ANC: lung 9 0 0 1 0 0 1 0 0 0 0 0 Lung Pain: chest/thorax 9 0 1 0 0 0 1 0 0 0 0 0 Lung Pain: throat/phar/lar 9 1 0 0 0 0 1 0 0 0 0 0 Lymphopenia 4 0 4 1 1 0 0 0 0 0 1 0 Metabolic/Lab-other 9 1 0 0 0 0 1 0 0 0 0 0 Mood alteration: anxiety 9 1 0 0 0 0 1 0 0 0 0 0 Mood alteration: depression 9 1 0 0 0 0 1 0 0 0 0 0 Mucositis, clin: oral cavity 9 0 1 0 0 0 0 0 1 0 0 0 Muscle weakness: whole body 9 0 1 0 0 0 1 0 0 0 0 0

Continued ABVD (n=10) BEACOPP (n=1) ADVERSE EVENTS 0 1 2 3 4 5 0 1 2 3 4 5 Musculo. Pain: back 8 2 0 0 0 0 1 0 0 0 0 0 Musculo. Pain: bone 8 2 0 0 0 0 1 0 0 0 0 0 Musculo. Pain: joint 9 0 0 1 0 0 1 0 0 0 0 0 Musculo. Pain: limb 9 0 1 0 0 0 1 0 0 0 0 0 Musculo. Pain: muscle 9 0 1 0 0 0 1 0 0 0 0 0 Nail changes 8 2 0 0 0 0 1 0 0 0 0 0 Nausea 4 2 4 0 0 0 1 0 0 0 0 0 Neuro Pain: head/headache 8 2 0 0 0 0 1 0 0 0 0 0 Neuropathy-motor 8 1 0 1 0 0 1 0 0 0 0 0 Neuropathy-sensory 5 3 1 1 0 0 0 1 0 0 0 0 Neutrophils 3 0 0 2 5 0 0 0 0 0 1 0 Pain-other 9 1 0 0 0 0 1 0 0 0 0 0 Platelets 7 2 0 1 0 0 0 1 0 0 0 0 Pruritus 9 0 1 0 0 0 1 0 0 0 0 0 Pulmonary-other 8 1 1 0 0 0 1 0 0 0 0 0 Rigors/chills 6 4 0 0 0 0 0 0 1 0 0 0 Sexual/Repro. Pain: urethra 9 1 0 0 0 0 1 0 0 0 0 0 Supra Arrhyth: Sinus Tachy. 9 1 0 0 0 0 1 0 0 0 0 0 Sweating 10 0 0 0 0 0 0 1 0 0 0 0 Taste alteration 9 1 0 0 0 0 1 0 0 0 0 0 Thrombosis/embolism 9 0 0 1 0 0 1 0 0 0 0 0 Vomiting 6 3 1 0 0 0 1 0 0 0 0 0 Weight Loss 9 1 0 0 0 0 1 0 0 0 0 0 MAX. GRADE ANY ADVERSE EVENT 1 0 0 3 6 0 0 0 0 0 1 0 Response Two Initial Cycles of ABVD Followed by Response-adapted Therapy HIV-positive Patients Continued ABVD BEACOPP N % N % Complete Response 9 90 0 0 Partial Response 1 10 1 100 Total 10 100 1 100 The LIFETEST Procedure Stratum 1: rowno = Initial ABVD APRIL 11-14, 2018 SWOG LYMPHOMA 28

100% Progression-Free Survival HIV-positive Patients 80% 60% 40% 20% 0% At Risk At Risk Failed 2-Year Estimate 12 4 83% At Risk 12 10 8 7 7 5 0 12 24 36 48 60 Months After Registration 100% Stratum The LIFETEST 1: rowno = Procedure Initial ABVD Overall Survival HIV-positive Patients 80% 60% 40% 20% 0% At Risk At Risk Deaths 2-Year Estimate 12 1 100% At Risk 12 11 10 9 9 8 0 12 24 36 48 60 Months After Registration APRIL 11-14, 2018 SWOG LYMPHOMA 29

S1608 Phase II Coordinating Group: SWOG Randomized Phase II Trial in Early Relapsing or Refractory Follicular Lymphoma Participants: SWOG, CTSU (Supported by Alliance, ECOG-ACRIN) Date Activated: 08/10/2017 Study Chairs: P Barr, B Link (Alliance), C Flowers (ECOG-ACRIN) Statisticians: H Li, M LeBlanc Data Coordinator: I Syquia SCHEMA R A N D O M I Z A T I O N TGR-1202 + Obinutuzumab Lenalidomide + Obinutuzumab CHOP + Obinutuzumab Objectives To compare the complete response rate at 6 cycles after randomization as defined by centrally read PET/CT (integral biomarker) of two targeted therapeutic regimens (obinutuzumab + TGR-1202 or obinutuzumab + lenalidomide) with obinutuzumab + CHOP in patients with early relapsing or refractory follicular lymphoma. To validate the prognostic association of the m7- FLIPI model, demonstrating that the population of follicular lymphoma patients who respond poorly to chemoimmunotherapy are enriched for having a high-risk m7-flipi score, and that the score is associated with progression-free survival (integrated biomarker). To estimate the 30 month sustained complete response rate (CR30) defined by centrally read PET/CT with each of the regimens in this early relapsing or refractory follicular lymphoma population. APRIL 11-14, 2018 SWOG LYMPHOMA 30 S1608/II

To estimate best response at 12 cycles of therapy, progression-free survival, duration of response, and overall survival with each of the combinations in early relapsing or refractory follicular lymphoma. To evaluate the adverse effects of each of the regimens in early relapsing or refractory follicular lymphoma. To evaluate the predictive performance of noninvasive genotyping (m7-flipi in circulating tumor DNA) of plasma at study entry relative to standard tumor genotyping (m7-flipi) of formalin-fixed paraffin-embedded tumor tissue. To evaluate the association between the detection of active lymphoma by PET/CT and the detection of circulating tumor DNA in plasma at baseline, after 6 and 12 cycles, and at 30 months after initiation of study therapy Patient Population Patients must have follicular lymphoma ( I, II or IIIa) confirmed at initial diagnosis and at relapse with identifiable FDG avid disease on PET/CT. Patients must not have involvement with large cell lymphoma. Patients must have either failed to achieve a complete remission, or must have relapsed within two years after completing first line of bendamustine-containing chemoimmunotherapy. Patients must have the components of Follicular Lymphoma International Prognostic Index (FLIPI) available from diagnosis and at time of registration. Additionally, patients must have beta-2- microglobulin collected at time of registration. Patients must not have clinical evidence of central nervous system involvement by lymphoma. Patients must have received at least three cycles of bendamustine as first line therapy. Patients may have additionally received maintenance anti-cd-20 antibody based therapy or consolidative radioimmunotherapy within two years of the last dose of the bendamustine therapy. Patients must have completed systemic therapy at least 21 days prior to registration or completed radio/mmunotherapy at least 84 days prior to registration. Patients must have recovered from all treatment related toxicities prior to registration. Patients must not have had prior anthracycline based therapy, or any prior treatment with any PI3K inhibitor or lenalidomide. Relapsed patients must not have received any intervening chemotherapy. Patients must be able and willing to take prophylaxis as listed in the protocol. Patients must be at least 18 years of age and have a Zubrod performance status of 0-2. Patients must have adequate renal, hepatic, cardiac and hematologic function. Patients with Hepatitis B virus infection, or Hepatitis C virus infection, or known HIV infection are eligible with restrictions. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 miu/ml within 10-14 days prior to registration. Stratification/Descriptive Factors Patient randomization will be stratified according to the following factors: (1) previous receipt of maintenance therapy: yes vs no; and (2) refractory status: lack of CR after completing first line bendamustine-containing chemoimmunotherapy vs disease relapse within two years of completing first line bendamustine-containing chemoimmunotherapy. If patients meet the definition of both refractory and relapsing within two years, they will be grouped with the refractory cohort. Accrual Goals The accrual goal for this study is 150 patients to achieve 135 eligible patients. Interim analyses are planned after response data for six cycles of treatment are available for half of patients on each arm. Summary Statement The trial opened to accrual on August 10, 2017. As of February 1, 2018, two patients had been registered to this study, one from Cancer Research Consortium of West Michigan and another from Washington University School of Medicine. APRIL 11-14, 2018 SWOG LYMPHOMA 31 S1608/II

EAY131 Master Protocol / Phase II Coordinating Group: ECOG-ACRIN NCI-MATCH: Molecular Analysis for Therapy Choice Participants: ECOG-ACRIN, CTSU Date Activated: 08/12/2015 Study Chairs: K Flaherty (ECOG-ACRIN), B Conley (NCI), P O'Dwyer (ECOG-ACRIN), A Chen (NCI), V Villalobos (SWOG) Molecular Profiling by Outside Lab SCHEMA Treatment for Molecular Profile of Interest Toxicity or Progression *As of May 1, 2017, patients must be screened via one of the outside laboratories listed in the protocol and only those patients with an applicable rare variant mutation of interest are eligible for subprotocol enrollment. Objectives To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/ multiple myeloma. To evaluate the proportion of patients alive and progression free at six months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma. To evaluate the time until death or disease progression. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, RNA, protein and imaging-based assessment platforms. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict Objective Response and Progression Free Survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens. Patient Population Patients must have histologically documented solid tumors or histologically confirmed diagnosis of lymphoma or multiple myeloma that has progressed following at least one line of standard systemic therapy and/or for whose disease no standard treatment exists that has been shown to prolong survival. Patients must have measurable disease and meet one of the criteria in the protocol regarding tissue procurement. Patients must not currently be receiving any other investigational agents. Any prior therapy, radiotherapy (except palliative radiation therapy of 30 Gy or less), or major surgery must have been completed at least four weeks prior to treatment on APRIL 11-14, 2018 SWOG LYMPHOMA 32 EAY131

NCI-MATCH and all adverse events due to prior therapy must have resolved to a 1 or better (except alopecia and lymphopenia) by start of treatment. Palliative radiation therapy must have been completed at least two weeks prior to start of treatment. Patients with brain metastases or primary brain tumors must have completed treatment, surgery, or radiation therapy at least four weeks prior to start of treatment. Patients must have discontinued steroids at least one week prior to registration and remain off steroids thereafter, except as permitted in the protocol. Patients with glioblastoma must have been on a stable dose of steroids, or be off steroids, for one week prior to registration to treatment step. Patients must not require the use of full dose coumarinderivative anticoagulants. Low molecular weight heparin is permitted for prophylactic or therapeutic use. Factor X inhibitors are permitted. Patients may receive non-protocol treatment after biopsy (if clinically indicated) until they receive notification of results, but patients may not enroll in another investigational study during this time and the therapy cannot be an arm in this trial. Patients must be at least 18 years of age, have an ECOG performance status of 0 or 1, must have a life expectancy of at least 3 months, and must be able to swallow tablets. Patients must have adequate hematologic, hepatic, renal, cardiac and marrow function. Patients must not have any uncontrolled intercurrent illness. HIV-positive patients are eligible provided they meet protocol criteria. Each subprotocol will have additional eligibility criteria that will be outlined in Section 2.0 of the agentspecific subprotocol. Only sites utilizing the CIRB as their IRB of record are able to participate in the trial. Accrual Goals The target screening accrual for this study is approximately 6,452 patients, with the goal of accruing 35 patients in each treatment subprotocol. If after screening 500 patients the total number of patients with actionable tumor alteration (therefore qualifying for treatment) is below 50, results will be presented to the steering committee for consideration of trial termination. Within any given subprotocol, if rate of enrollment is such that it is unlikely accrual can reach 25 patients by the time the overall study screening accrual goal is met, and if 13 patients have been treated and no responses have been observed, then the steering committee may consider terminating accrual in that subgroup due to lack of feasibility. After 500 patients are screened, the study design will be reassessed to assure its appropriateness. An interim analysis of the assay results will be performed after biopsies from approximately the first 200 patients are processed. Summary Statement As of May 15, 2017, biopsy material is no longer accepted for testing by a MATCH trial laboratory. Patients must now be screened via one of the outside laboratories listed in the protocol and only those patients with an applicable rare variant mutation of interest are eligible for a molecularly guided subprotocol. See the CTSU website for the list of subprotocols currently enrolling patients. ECOG-ACRIN reported a total of 6,482 screened patients and 743 patients enrolled for treatment as of December 31, 2017. This includes 891 screened and 102 molecularly matched SWOG registrations. See the Early Therapeutics & Rare Cancers chapter for the most recent summary from ECOG-ACRIN. APRIL 11-14, 2018 SWOG LYMPHOMA 33 EAY131