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Purpose: Patients with bulky stage I/II classic Hodgkin lymphoma (cHL) are typically treated with chemotherapy followed by radiation. Late effects associated with radiotherapy include increased risk of second cancer and cardiovascular disease. We tested a positron emission tomography (PET)-adapted approach in patients with bulky, early-stage cHL, omitting radiotherapy in patients with interim PET-negative (PET-) disease and intensifying treatment in patients with PET-positive (PET+) disease., Methods: Eligible patients with bulky disease (mass > 10 cm or 1/3 the maximum intrathoracic diameter on chest x-ray) received two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by interim fluorodeoxyglucose PET (PET2). Patients with PET2-, defined as 1-3 on the 5-point scale, received four additional cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine. Patients with PET2+ received four cycles of escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone followed by 30.6 Gy involved-field radiation., Results: Of 94 evaluable patients, 53% were female with median age 30 years (range, 18-58 years). Eight-five (90%) had stage II disease, including 48 (51%) with stage IIB/IIBE. Seventy-eight (78%) were PET2- and 21 (22%) were PET2+. The predominant toxicity was neutropenia, with 9% of patients developing febrile neutropenia and one developing sepsis. The primary end point of 3-year progression-free survival (PFS) was 93.1% in PET2- and 89.7% in PET2+ patients. Three-year overall survival was 98.6% and 94.4%, respectively. The estimated hazard ratio comparing PFS of patients with PET2+ and patients with PET2- was 1.03 (85% upper bound 2.38) and was significantly less than the null hypothesis of 4.1 (one-sided P = .04)., Conclusion: Our study of PET-adapted therapy in bulky stage I/II cHL met its primary goal and was associated with an excellent 3-year PFS rate of 92.3% in all patients, with the majority being spared radiotherapy and exposure to intensified chemotherapy.

Purpose: Lenalidomide combined with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) (R2CHOP) in untreated diffuse large B-cell lymphoma (DLBCL) has shown promising activity, particularly in the activated B-cell-like (ABC) subtype. Eastern Cooperative Oncology Group (ECOG)-ACRIN trial E1412 was a randomized phase II study comparing R2CHOP versus R-CHOP in untreated DLBCL., Patients and Methods: Patients with newly diagnosed DLBCL, stage II bulky-IV disease, International Prognostic Index (IPI) ≥ 2, and ECOG performance status ≤ 2 were eligible and randomly assigned 1:1 to R2CHOP versus R-CHOP for six cycles. Tumors were analyzed using the NanoString Lymph2Cx for cell of origin. The primary end point was progression-free survival (PFS) in all patients with the co-primary end point of PFS in ABC-DLBCL. Secondary end points included overall response rate (ORR), complete response (CR) rate, and overall survival (OS)., Results: Three hundred forty-nine patients were enrolled; 280 patients (145 R2CHOP and 135 R-CHOP) were evaluable: 94 were ABC-DLBCL, 122 germinal center B-cell-like-DLBCL, 18 unclassifiable, and 46 unknowns. Baseline characteristics were well-balanced between arms, and the median age was 66 (range, 24-92); 70% of patients had stage IV disease; 34%, 43%, and 24% had IPI 2, 3, and 4 or 5, respectively. Myelosuppression was more common in the R2CHOP arm. The ORR and CR rate were 92% and 68% in R-CHOP and 97% ( P = .06) and 73% ( P = .43) in the R2CHOP arm, respectively. The median follow-up was 3.0 years; R2CHOP was associated with a 34% reduction in risk of progression or death versus R-CHOP (hazard ratio [HR], 0.66 95% CI, 0.43 to 1.01) and 3-year PFS of 73% versus 61%, one-sided P = .03, and an improvement in OS (83% and 75% at 3 years; HR, 0.67; one-sided P = .05). The PFS HR for R2CHOP was 0.67 for ABC-DLBCL, one-sided P = .1., Conclusion: In this signal-seeking study, the addition of lenalidomide to R-CHOP (R2CHOP) improved outcomes in newly diagnosed DLBCL including patients with ABC-DLBCL., Competing Interests: Grzegorz S. NowakowskiConsulting or Advisory Role: Celgene/BMS, MorphoSys, Genentech, Roche Selvita, Debiopharm Group, Kite/Gilead, Karyopharm TherapeuticsResearch Funding: Celgene/BMS, NanoString Technologies, MorphoSys Roche, Seattle Genetics Fangxin HongConsulting or Advisory Role: Merck Sharp & Dohme David W. ScottConsulting or Advisory Role: Celgene/BMS, Janssen, AbbVie, AstraZenecaResearch Funding: Janssen, Roche/Genentech, NanoString TechnologiesPatents, Royalties, Other Intellectual Property: Named inventor on a pending patent describing gene expression profiling in prognostication in classical Hodgkin lymphoma, As a member of the LLMPP I am potentially a named inventor on a pending patent on the use of gene expression profiling to assign cell-of-origin in diffuse large B-cell lymphoma, I am a named inventor on a pending patent on the use of gene expression profiling to determine the proliferation signature in mantle cell lymphoma, Named inventor on a pending patent describing using gene expression profiling to identify molecular subtypes of GCB-DLBCL Rebecca L. KingResearch Funding: Celgene/BMS Thomas M. HabermannConsulting or Advisory Role: Celgene/BMS, Kite/Gilead Nina Wagner-JohnstonConsulting or Advisory Role: ADC Therapeutics, Bayer, Regeneron, Calibr, Verastem, Gilead SciencesResearch Funding: Merck, Novartis/Pfizer, Genentech, Astex Pharmaceuticals, Juno Therapeutics, Regeneron, Acerta Pharma, ADC Therapeutics Carla CasuloHonoraria: Gilead SciencesResearch Funding: Celgene/BMS, Verastem, Gilead SciencesTravel, Accommodations, Expenses: Gilead Sciences, Roche James L. WadeEmployment: Johnson & JohnsonStock and Other Ownership Interests: Celgene/BMS, Abbott, GlaxoSmithKline, Johnson & Johnson, NovartisConsulting or Advisory Role: New Century Health Jonathon B. CohenConsulting or Advisory Role: Celgene/BMS, Seattle Genetics, Abbvie, Janssen, Loxo, Kite/Gilead, AstraZeneca, Cellectar, Aptitude MedicalResearch Funding: Bristol-Myers Squibb, Janssen, Novartis, Takeda, AI Therapeutics, Genentech, ASH, Lymphoma Research Foundation, Loxo, Bioinvent, AstraZeneca Nadia KhanHonoraria: JanssenConsulting or Advisory Role: IncyteResearch Funding: Bristol-Myers Squibb Jennifer E. AmengualHonoraria: Janssen, Daiichi Sankyo, Karyopharm TherapeuticsResearch Funding: Appia PharmaceuticalsTravel, Accommodations, Expenses: Epizyme John P. LeonardConsulting or Advisory Role: Celgene/BMS, Bristol-Myers Squibb, Gilead Sciences, Epizyme, Bayer, Genentech/Roche, ADC Therapeutics, MEI Pharma, AstraZeneca, Merck, Morphosys, Nordic Nanovector, Karyopharm Therapeutics, Sutter Medical Group, Miltenyi Biotec, Regeneron, Bayer, Akcea Therapeutics, Sandoz, Nordic Nanovector, Genmab, Abbvie, IncyteResearch Funding: Research Funding: Celgene/BMS, Alliance for Clinical Trials in Oncology, Takeda, Pfizer, National Cancer Institute, Janssen Oncology, EpizymeTravel, Accommodations, Expenses: BeiGene Jonathan W. FriedbergConsulting or Advisory Role: Astellas Pharma, NovartisResearch Funding: Seattle GeneticsPatents, Royalties, Other Intellectual Property: Patient on bone marrow microenvironment signals Lale KostakogluConsulting or Advisory Role: Roche/Genentech Brad S. KahlConsulting or Advisory Role: Celgene/BMS, Juno Therapeutics, Abbvie, Pharmacyclics, Acerta Pharma, ADC Therapeutics, Pharmacyclics, Genentech, Roche, AstraZeneca, BeiGene, Bayer, MEI Pharma, TG Therapeutics, Kite/Gilead, MorphoSys, JanssenResearch Funding: Genentech, Acerta Pharma, ADC Therapeutics, Celgene/BMSTravel, Accommodations, Expenses: Celgene/BMS, Juno Therapeutics, Genentech/Roche, Abbvie, Millennium, Seattle Genetics Thomas E. WitzigConsulting or Advisory Role: Karyopharm Therapeutics, Abbvie/Genentech, Seattle Genetics, Celgene/BMS, Incyte, Epizyme, Cellectar, Tessa Therapeutics, Portola Pharmaceuticals, MorphoSys, ADC TherapeuticsResearch Funding: Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm TherapeuticsPatents, Royalties, Other Intellectual Property: T.E.W. is co-inventor on a patent application filed by Mayo Clinic and pending on the combination of CRM1 inhibitors with salicylates.No other potential conflicts of interest were reported.

Purpose: Diagnosis of AIDS lymphoma in low-resource settings, like South Africa, is often delayed, leaving patients with limited treatment options. In tuberculosis (TB) endemic regions, overlapping signs and symptoms often lead to diagnostic delays. Assessment of plasma cell-free DNA (cfDNA) by next-generation sequencing (NGS) may expedite the diagnosis of lymphoma but requires high-quality cfDNA., Methods: People living with HIV with newly diagnosed aggressive B-cell lymphoma and those with newly diagnosed TB seeking care at Chris Hani Baragwanath Academic Hospital and its surrounding clinics, in Soweto, South Africa, were enrolled in this study. Each participant provided a whole blood specimen collected in cell-stabilizing tubes. Quantity and quality of plasma cfDNA were assessed. NGS of the immunoglobulin heavy chain was performed., Results: Nine HIV+ patients with untreated lymphoma and eight HIV+ patients with TB, but without lymphoma, were enrolled. All cfDNA quantity and quality metrics were similar between the two groups, except that cfDNA accounted for a larger fraction of recovered plasma DNA in patients with lymphoma. The concentration of cfDNA in plasma also trended higher in patients with lymphoma. NGS of immunoglobulin heavy chain showed robust amplification of DNA, with large amplicons (> 250 bp) being more readily detected in patients with lymphoma. Clonal sequences were detected in five of nine patients with lymphoma, and none of the patients with TB., Conclusion: This proof-of-principle study demonstrates that whole blood collected for cfDNA in a low-resource setting is suitable for sophisticated sequencing analyses, including clonal immunoglobulin NGS. The detection of clonal sequences in more than half of patients with lymphoma shows promise as a diagnostic marker that may be explored in future studies., Competing Interests: Moosa PatelHonoraria: Roche/Genentech, Novartis, Janssen, Novartis South Africa, Amgen, RocheConsulting or Advisory Role: Janssen Research & Development, Pfizer, Janssen, NovartisResearch Funding: RocheTravel, Accommodations, Expenses: Janssen, Roche, Novartis Vinitha PhilipTravel, Accommodations, Expenses: Roche Philippa AshmoreConsulting or Advisory Role: Novartis, Janssen, TakedaTravel, Accommodations, Expenses: Takeda, Key Oncologics, Cipla, Sanofi Wendy StevensResearch Funding: Roche, Abbott Laboratories, Cepheid Nina Wagner-JohnstonConsulting or Advisory Role: ADC Therapeutics, Bayer, Regeneron, Calibr, Verastem, Gilead SciencesResearch Funding: Merck, Novartis/Pfizer, Genentech, Astex Pharmaceuticals, Juno Therapeutics, Regeneron, Acerta Pharma, ADC Therapeutics Christopher D. GockeLeadership: OncoMEDx IncStock and Other Ownership Interests: OncoMEDx IncPatents, Royalties, Other Intellectual Property: Intellectual property licensed from Penn State to my company, OncoMEDx, Inc Neil A. MartinsonResearch Funding: Pfizer Rena R. XianHonoraria: InvivoscribeTravel, Accommodations, Expenses: InvivoscribeNo other potential conflicts of interest were reported.

Purpose: To update the ASCO guideline on the recommended prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathy (CIPN) in adult cancer survivors., Methods: An Expert Panel conducted targeted systematic literature reviews to identify new studies., Results: The search strategy identified 257 new references, which led to a full-text review of 87 manuscripts. A total of 3 systematic reviews, 2 with meta-analyses, and 28 primary trials for prevention of CIPN in addition to 14 primary trials related to treatment of established CIPN, are included in this update., Recommendations: The identified data reconfirmed that no agents are recommended for the prevention of CIPN. The use of acetyl-l-carnitine for the prevention of CIPN in patients with cancer should be discouraged. Furthermore, clinicians should assess the appropriateness of dose delaying, dose reduction, substitutions, or stopping chemotherapy in patients who develop intolerable neuropathy and/or functional impairment. Duloxetine is the only agent that has appropriate evidence to support its use for patients with established painful CIPN. Nonetheless, the amount of benefit from duloxetine is limited.Additional information is available at www.asco.org/survivorship-guidelines.

Purpose: Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by cyclin D1 expression. Autologous hematopoietic cell transplantation (AHCT) consolidation after induction chemotherapy is often used for eligible patients; however, the benefit remains uncertain in the rituximab era. Herein we retrospectively assessed the impact of AHCT consolidation on survival in a large cohort of transplantation-eligible patients age 65 years or younger., Patients and Methods: We retrospectively studied transplantation-eligible adults age 65 years or younger with newly diagnosed MCL treated between 2000 and 2015. The primary objective was to assess for improved progression-free survival (PFS) with AHCT consolidation and secondarily to assess for improved overall survival (OS). Cox multivariable regression analysis and propensity score-weighted (PSW) analysis were performed., Results: Data were collected from 25 medical centers for 1,254 patients; 1,029 met inclusion criteria. Median follow-up for the cohort was 76 months. Median PFS and OS were 62 and 139 months, respectively. On unadjusted analysis, AHCT was associated with improved PFS (75 v 44 months with v without AHCT, respectively; P < .01) and OS (147 v 115 months with v without AHCT, respectively; P < .05). On multivariable regression analysis, AHCT was associated with improved PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66; P < .01) and a trend toward improved OS (HR, 0.77; 95% CI, 0.59 to 1.01; P = .06). After PSW analysis, AHCT remained associated with improved PFS (HR, 0.70; 95% CI, 0.59 to 0.84; P < .05) but not improved OS (HR, 0.87; 95% CI, 0.69 to 1.1; P = .2)., Conclusion: In this large cohort of younger, transplantation-eligible patients with MCL, AHCT consolidation after induction was associated with significantly improved PFS but not OS after PSW analysis. Within the limitations of a retrospective analysis, our findings suggest that in younger, fit patients, AHCT consolidation may improve PFS.

Purpose: To provide evidence-based guidance on the optimum prevention and treatment approaches in the management of chemotherapy-induced peripheral neuropathies (CIPN) in adult cancer survivors., Methods: A systematic literature search identified relevant, randomized controlled trials (RCTs) for the treatment of CIPN. Primary outcomes included incidence and severity of neuropathy as measured by neurophysiologic changes, patient-reported outcomes, and quality of life., Results: A total of 48 RCTs met eligibility criteria and comprise the evidentiary basis for the recommendations. Trials tended to be small and heterogeneous, many with insufficient sample sizes to detect clinically important differences in outcomes. Primary outcomes varied across the trials, and in most cases, studies were not directly comparable because of different outcomes, measurements, and instruments used at different time points. The strength of the recommendations is based on the quality, amount, and consistency of the evidence and the balance between benefits and harms., Recommendations: On the basis of the paucity of high-quality, consistent evidence, there are no agents recommended for the prevention of CIPN. With regard to the treatment of existing CIPN, the best available data support a moderate recommendation for treatment with duloxetine. Although the CIPN trials are inconclusive regarding tricyclic antidepressants (such as nortriptyline), gabapentin, and a compounded topical gel containing baclofen, amitriptyline HCL, and ketamine, these agents may be offered on the basis of data supporting their utility in other neuropathic pain conditions given the limited other CIPN treatment options. Further research on these agents is warranted., (© 2014 by American Society of Clinical Oncology.)