Faculty Bibliography

In a Phase Ib/II trial of patients (pts) with relapsed/refractory follicular lymphoma (R/R FL), polatuzumab vedotin (Pola) + obinutuzumab (G) showed activity and tolerability (Phillips et al. Blood 2016). A Phase II study of the doublet combination of G + lenalidomide (Len) showed activity and acceptable safety in pts with R/R FL (Morschhauser et al. Lancet 2019). Here, we present the full primary analysis of efficacy and safety of Pola-G-Len in pts with R/R FL from the Phase Ib/II study, GO29834 (NCT02600897). GO29834 is an open-label, multicentre study of pts with R/R FL (Grade <3b) who had received >=1 prior anti-CD20-containing chemo-immunotherapy regimen. The recommended Phase II dose (RP2D) for Pola+Len was defined in a 3+3 dose-escalation phase. In the Phase II expansion cohort, pts received induction treatment with six 28-day cycles of: G 1000 mg IV (Cycle [C]1: Day [D]1, D8, D15; C2-6: D1); Pola 1.4 mg/kg IV (D1), Len 20 mg PO (D1-21). Responders received maintenance treatment for 24 months: G 1000 mg (D1 every 2 months); Len 10 mg (D1-21, Months 1-12). The primary endpoint was Independent Review Committee (IRC)-assessed complete response (CR) at end of induction (EOI), based on positron emission tomography-computed tomography (PET-CT) scans (modified Lugano 2014 criteria). Progression-free survival (PFS) was assessed by the investigator. As of 12 August 2019, 56 pts were enrolled and had entered induction (Phase Ib/II cohorts); median follow-up was 16.6 and 15.1 months in safety- and efficacy-evaluable populations, respectively. Baseline characteristics were: median age, 62 years; male, 59%; Ann Arbor Stage III-IV, 88%; Follicular Lymphoma International Prognostic Index high-risk (>=3), 55%; bulky disease (>=7 cm), 16%; >=2 prior lines of therapy, 77%; refractory to last line of prior therapy/ any anti-CD20 treatment, 59%/71%, respectively. All pts had >=1 adverse event (AE), 32 (57%) had a serious AE, 47 (84%) had a Grade 3-4 AE. The most common Grade 3-4 AEs were neutropenia (n = 31, 55%), thrombocytopenia (n = 15, 27%), infections (n = 11, 20%), and anaemia (n = 8, 14%). AEs led to dose reduction or interruption of any drug in 19 (34%) and 43 (77%) of pts, respectively; the majority were modifications of Len. AEs led to the discontinuation of any study drug in 17 (30%) pts. One Grade 5 AE was reported (septic shock); this was not considered study treatmentrelated as the pt was receiving a new anti-lymphoma treatment following disease progression (PD). In the primary efficacy population (n = 46), the IRC-assessed objective response rate was 76%, the CR rate was 63% (Table). Subgroup analysis showed that 60% (15/25) of pts who were refractory to their last treatment achieved a CR. Median PFS was not reached. Our study of the novel triplet combination, Pola-G-Len demonstrates a safety profile consistent with the known profiles of the individual drugs. CR rates at EOI were high in this heavily pre-treated and refractory population, which compares favourably with currently available R/R FL therapies. These findings support further investigation of Pola-G-Len in a larger pt population. Follow-up is ongoing to determine the median PFS

PURPOSE OF REVIEW/OBJECTIVE:Antibody-drug conjugates are a new class of therapeutic agents in the treatment of B cell malignancies. In this review, we summarize the recent developments of polatuzumab vedotin in the treatment of relapsed or refractory diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL). RECENT FINDINGS/RESULTS:Polatuzumab vedotin recently received its first FDA approval in combination with bendamustine and rituximab for the treatment of patients with relapsed or refractory DLBCL. Polatuzumab vedotin has been evaluated and is being studied in combinations with chemoimmunotherapy, immunomodulating agents, bispecific antibodies, and venetoclax. These studies have shown promising results in early phase trials. While further studies in a larger patient population are needed in order to determine an optimal combination regimen for polatuzumab vedotin, the ongoing trials represent a growing list of potential therapeutic options for the patients with relapsed or refractory NHL and newly diagnosed NHL alike.

A MESSAGE FROM ASCO’S PRESIDENT/UNASSIGNED:report tells part of this story, sharing the most transformative research of the past year. The report also includes our latest thinking on the most urgent research priorities in oncology.ASCO's 2020 Advance of the Year-Refinement of Surgical Treatment of Cancer-highlights how progress drives more progress. Surgery has played a fundamental role in cancer treatment. It was the only treatment available for many cancers until the advent of radiation and chemotherapy. The explosion in systemic therapies since then has resulted in significant changes to when and how surgery is performed to treat cancer. In this report, we explore how treatment successes have led to less invasive approaches for advanced melanoma, reduced the need for surgery in renal cell carcinoma, and increased the number of patients with pancreatic cancer who can undergo surgery.Many research advances are made possible by federal funding. With the number of new US cancer cases set to rise by roughly a third over the next decade, continued investment in research at the national level is crucial to continuing critical progress in the prevention, screening, diagnosis, and treatment of cancer.While clinical research has translated to longer survival and better quality of life for many patients with cancer, we can't rest on our laurels. With ASCO's Research Priorities to Accelerate Progress Against Cancer, introduced last year and updated this year, we've identified the critical gaps in cancer prevention and care that we believe to be most pressing. These priorities are intended to guide the direction of research and speed progress.Of course, the effectiveness or number of new treatments is meaningless if patients don't have access to them. High-quality cancer care, including clinical trials, is out of reach for too many patients. Creating an infrastructure to support patients is a critical part of the equation, as is creating connections between clinical practices and research programs. We have much work to do before everyone with cancer has equal access to the best treatments and the opportunity to participate in research. I know that ASCO and the cancer community are up for this challenge.Sincerely,Howard A. "Skip" Burris III, MD, FACP, FASCOASCO President, 2019-2020.

PURPOSE OF REVIEW/OBJECTIVE:The landscape of relapsed or refractory (R/R) Hodgkin lymphoma (HL) treatment has changed significantly since the FDA approval of brentuximab vedotin in 2011. In this review, we summarize the recent advances in the therapy for R/R classical Hodgkin lymphoma (cHL). RECENT FINDINGS/RESULTS:Immunotherapies with pembrolizumab, nivolumab, and ipilimumab, and chimeric antigen receptor (CAR) T cell therapies have shown promising results in early phase trials. Other novel agents under investigation include targeted therapies with histone deacetylase inhibitors, Janus kinase 2 inhibitors, and immunomodulators. While further studies with larger populations and longer follow-up times are needed to determine the safe and effective combinations, these novel approaches represent a growing list of treatment options that are on the horizon to improve the cure rate and increase duration of remission for R/R HL patients.

BACKGROUND:Salvage immunochemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation is the standard-of-care second-line treatment for patients with relapsed/refractory diffuse large B-cell lymphoma after first-line R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Outcomes after receipt of second-line immunochemotherapy in patients with aggressive B-cell lymphomas who relapse or are refractory to intensive first-line immunochemotherapy regimens (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab [R-EPOCH], rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone alternating with methotrexate and cytarabine [R-HyperCVAD], rituximab, cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate alternating with ifosfamide, etoposide, and cytarabine [R-CODOX-M/IVAC]) remain unknown. METHODS:Outcomes of patients with non-Burkitt, aggressive B-cell lymphomas and relapsed/refractory disease after first-line treatment with intensive immunochemotherapy regimens who received platinum-based second-line immunochemotherapy were reviewed retrospectively. Analyses were performed to determine progression-free survival (PFS) and overall survival (OS) from the time of receipt of second-line immunochemotherapy. RESULTS:In total, 195 patients from 19 academic centers were included in the study. The overall response rate to second-line immunochemotherapy was 44%, with a median PFS of 3 months and a median OS of 8 months. Patients with early treatment failure (primary refractory or relapse <12 months from completion of first-line therapy) experienced inferior median PFS (2.8 vs 23 months; P < .001) and OS (6 months vs not reached; P < .001) compared with patients with late treatment failure. Although the 17% of patients with early failure who achieved a complete response to second-line immunochemotherapy experienced prolonged survival, this outcome could not be predicted by clinicopathologic features at the start of second-line immunochemotherapy. CONCLUSIONS:Patients with early treatment failure after intensive first-line immunochemotherapy experience poor outcomes after receiving standard second-line immunochemotherapy. The use of standard-of-care or experimental therapies currently available in the third-line setting and beyond should be investigated in the second-line setting for these patients.

Background: The Bruton's tyrosine kinase inhibitor ibrutinib is highly effective as a monotherapy in relapsed/refractory mantle cell lymphoma (MCL) with an overall response rate of 68% (Wang et al, NEJM 2013), but the duration of response is shorter than what is seen in chronic lymphocytic leukemia, and the survival of patients who progress after receiving ibrutinib is as short as 3 months (Martin et al, Blood, 2016). In addition, the complete response (CR) rate is only 21%. Ibrutinib-containing combinations may improve depth and duration of response in patients with relapsed/refractory MCL. While use of the proteasome inhibitor, bortezomib, can be limited due to the development of peripheral neuropathy, it has an ORR of 33% (CR rate 8%) in MCL, and preclinical models suggest a synergism between proteasome inhibitors and ibrutinib in MCL cell lines (Axelrod et al, Leukemia 2014). We developed a phase 1/2 trial of ibrutinib combined with the oral proteasome inhibitor ixazomib in patients with relapsed/refractory MCL. XXMethod(s): PrE0404 will be open at 18 sites nationwide and is registered at clinicaltrials.gov (NCT03323151). It is currently enrolling patients with relapsed/refractory MCL who have received at least 1 prior line of combination therapy. Patients receiving prior BTK or proteasome inhibitors are eligible, and patients may have received prior autologous or allogeneic transplantation as long as they do not have active graft versus host disease. Patients must have <= grade 1 peripheral neuropathy. For phase 1, patients are required to have been off of a BTK inhibitor for 3 months. Starting dose of ibrutinib for all patients is 560mg daily, and dose levels of ixazomib for the phase 1 trial range from 3mg to 4mg days 1, 8, and 15 of a 28 day cycle. Patients continued therapy until disease progression or unacceptable toxicity. For the phase 1 portion of the study, patients are monitored for a dose limiting toxicity (DLT) during cycle 1, defined as grade 3 thrombocytopenia with significant bleeding, select grade 3 non-hematologic toxicities, grade 4 thrombocytopenia, grade 4 febrile neutropenia, grade 4 non-hematologic toxicity, or any grade 5 toxicity. In addition, any toxicity-related dose delay > 7 days of ibrutinib or ixazomib or an inability to receive all 3 doses of ixazomib during cycle 1 are considered DLT's. The maximum tolerated dose/recommended phase 2 dose will be the dose at which fewer than 1/6 patients experience a DLT, with the maximum dose of ixazomib will be 4mg. The primary endpoint for the phase 2 portion of the study is CR rate, and patients will be assigned to one of two cohorts based on prior BTK-inhibitor exposure. For ibrutinib-naive patients, we will target a CR rate of 40% (based on a historical CR rate of 21% for ibrutinib), and for ibrutinib-pretreated patients, we will target a CR rate of 23% (based on a historical CR rate of 8% for bortezomib). There is 86% statistical power & a one-sided 10% alpha to test each hypothesis. We will accrue 31 patients to each cohort in order to detect this difference. Secondary and exploratory endpoints will include progression-free and overall survival, overall response, toxicity, frequency of BTK mutations, and response based on molecular risk stratification. As of July 2019 the study is open to accrual at 14 sites and is expected to move to phase 2 in fall 2019, at which time it will be expanded to 18 sites. Disclosures: Cohen: Hutchison: Research Funding; Seattle Genetics, Inc.: Consultancy, Research Funding; Bristol-Meyers Squibb Company: Research Funding; Genentech, Inc.: Consultancy, Research Funding; Janssen Pharmaceuticals: Consultancy; Astra Zeneca: Research Funding; LAM Therapeutics: Research Funding; Lymphoma Research Foundation: Research Funding; ASH: Research Funding; UNUM: Research Funding; Gilead/Kite: Consultancy; Takeda Pharmaceuticals North America, Inc.: Research Funding. Portell: Infinity: Research Funding; Roche/Genentech: Research Funding; Xencor: Research Funding; TG Therapeutics: Research Funding; Acerta/AstraZeneca: Research Funding; Kite: Consultancy, Research Funding; Bayer: Consultancy; AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Amgen: Consultancy; BeiGene: Consultancy, Research Funding. Hamadani: ADC Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; Sanofi Genzyme: Research Funding, Speakers Bureau; Otsuka: Research Funding; Celgene: Consultancy; Merck: Research Funding; Medimmune: Consultancy, Research Funding; Takeda: Research Funding; Pharmacyclics: Consultancy. Diefenbach: Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding; Genentech: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; MEI: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Millenium/Takeda: Research Funding; Trillium: Research Funding. Landsburg: Celgene: Membership on an entity's Board of Directors or advisory committees; Triphase: Research Funding; Triphase: Research Funding; Takeda: Research Funding; Takeda: Research Funding; Seattle Genetics: Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau. Kahl: Seattle Genetics: Consultancy; ADC Therapeutics: Consultancy, Research Funding; BeiGene: Consultancy; TG Therapeutics: Consultancy. OffLabel Disclosure: Ixazomib is not currently approved for mantle cell lymphoma.XXCopyright

Introduction: Historically, outcomes for BL have improved in adults using dose intensive chemotherapy regimens and early CNS prophylaxis. More recent data using a less intensive regimen, DA-EPOCH, have been reported. We analyzed detailed patient (pt) & disease characteristics and treatment patterns across 26 US CCs over a recent 9 year (yr) period and also determined survival rates & prognostication. XXMethod(s): We conducted a large multicenter retrospective study of newly diagnosed (dx) adult BL pts (6/2009 - 6/2018). Dx was established by institutional expert pathology review; all cases were verified for BL based on 2016 WHO criteria (high grade B cell lymphoma, BL like, etc were excluded). Survival rates were estimated by Kaplan-Meier with differences assessed by log rank test. Univariate (UVA) associations were derived via Cox model with variables P <=0.05 entered stepwise into a multivariate (MVA) model. Using significant factors from the MVA, a prognostic survival model was constructed. XXResult(s): Among N=557 verified BL cases, clinical features included: median age 47 yrs (17-88 yrs; 24% >=60 yrs); male 76%; HIV+ 22%; ECOG PS 0/1 76%; B symptoms 51%; elevated LDH 78% (3, 5, & 10x elevation: 44%, 29% & 15%, respectively); hemoglobin <10.5 gm/dL 32%; albumin <3.5 30%; bone marrow (BM) involved 35%; non-BM extranodal (EN) in 80%; >1 EN 43%; and 76% stage 3-4 disease (10% stage 1). Additionally, 16% and 3% of pts had baseline leptomeningeal (CSF or cranial nerve palsy) or parenchymal CNS involvement, respectively (see Zayac A et al. ASH 2019 for details). For MYC partner, 68% had t(8;14), 4% light chain, 5% negative FISH (otherwise classic BL) and 23% + break apart probe. HIV+ pts had several clinical differences: CSF+ 23% vs 12% P=0.003; CNS 19% vs 8% P<0.001; ECOG PS 2-4 32% vs 21% P=0.002; BM 64% vs 34% P=0.03; and >1 EN 60% vs 38% P<0.001. For all pts, 87% had Tx at an academic CC (13% at community CC). Tx regimens were: CODOX-M/IVAC (Magrath) 31%, HyperCVAD/MA 29%, DA-EPOCH 28%, other 10% (mostly CHOP-based & CALGB Tx) & 1% were never treated. 90% of pts received rituximab as part of Tx (69% inpatient (inpt) & 31% outpatient) & 2% had consolidative autologous SCT. Response among all pts were CR 72%, PR 6%, SD 1%, PD 14%, 7% not evaluable. The treatment related mortality (TRM) rate across all pts was 8.9% (HIV+ vs not: 13% vs 8% P=0.09); most common: sepsis 48%, GI bleed/perforation 14% & respiratory failure 12%. TRM by Tx: hyperCVAD/MA 11.5%, EPOCH 6.4%, Magrath 6.3% & other 18.9%. With 39 month median follow-up, 3 year progression-free survival (PFS) and overall survival (OS) were 65% and 72%, respectively (Fig 1A). Among all pts who experienced disease progression, 90% occurred <12 months from dx (4% after 2 yrs). There were 20 cases (4%) of 2XX cancers seen including 7 secondary MDS/AML (median 26 months) & 6 cases of Hodgkin or other NHL (median 54 months). For prognostication, outcomes were inferior for pts ages >=40 yrs & LDH >3x normal (Fig 1B/C). Notably, survival rates were not different based on HIV status (Fig 1D) or by the 3 most common Tx regimens (Fig 1E). However, there were important Tx differences based on presence of CNS involvement (see Zayac A et al. ASH 2019). Additionally, use of rituximab was associated with improved PFS & OS (Fig 1F), while outcomes were similar whether rituximab was given inpt vs outpatient (inpt PFS HR 1.25, P=0.19). Furthermore, Tx at an academic CC was associated with improved outcomes, which persisted on MVA (PFS HR 0.54, 95%CI 0.33-0.88 P=0.01; OS HR 0.50, 95%CI 0.29-0.87 P=0.01) & achievement of initial CR was strongly prognostic (Fig 1G). Baseline factors significant on UVA for PFS & OS were: age >=40 yrs; PS 2-4; LDH >3x; anemia, low albumin; BM involvement; Stage 3-4; CSF+; & >1 EN. On MVA, factors associated with inferior survival were: age >=40 yrs (PFS HR 1.57, P<0.001; OS HR 1.89, P=0.001); PS 2-4 (PFS HR 1.57, P=0.002; OS HR 2.16, PXX3x (PFS HR 2.28, P<0.0001; OS HR 1.96, P<0.0001). Collectively, these factors yielded a BL survival model (Fig 1H/I). XXConclusion(s): Outcomes for adult BL in this contemporary, large, multicenter RW analysis appear inferior to smaller published series. Interestingly, despite increased adverse prognostic factors, survival rates appeared similar in HIV+ pts. In addition, use of rituximab, achievement of initial CR, and Tx at an academic CC were associated with improved survival. Finally, a novel BL-specific survival model identified pts with markedly divergent outcomes. [Formula presented] Disclosures: Evens: Seattle Genetics: Consultancy, Honoraria, Research Funding; Epizyme: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; Tesaro: Research Funding; Verastem: Consultancy, Honoraria. Danilov: Janssen: Consultancy; Seattle Genetics: Consultancy; MEI: Research Funding; Abbvie: Consultancy; Pharmacyclics: Consultancy; Takeda Oncology: Research Funding; Janssen: Consultancy; TG Therapeutics: Consultancy; Curis: Consultancy; Pharmacyclics: Consultancy; Aptose Biosciences: Research Funding; Verastem Oncology: Consultancy, Other: Travel Reimbursement, Research Funding; AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Bayer Oncology: Consultancy, Research Funding; Celgene: Consultancy; Bristol-Meyers Squibb: Research Funding; MEI: Research Funding; Gilead Sciences: Consultancy, Research Funding; Abbvie: Consultancy; Bristol-Meyers Squibb: Research Funding. Reddy: KITE Pharma: Consultancy; BMS: Consultancy, Research Funding; Celgene: Consultancy; Genentech: Research Funding; Abbvie: Consultancy. Farooq: Celgene: Honoraria; Kite Pharma: Research Funding. Khan: Janssen: Other: Educational Content/Symposium; Abbvie: Membership on an entity's Board of Directors or advisory committees; Bristol Myers: Other: Research Funds; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Yazdy: Genentech: Research Funding; Bayer: Honoraria; Abbvie: Consultancy; Octapharma: Consultancy. Karmali: Gilead/Kite; Juno/Celgene: Consultancy, Speakers Bureau; Astrazeneca: Speakers Bureau; Takeda, BMS: Other: Research Funding to Institution. Martin: Janssen: Consultancy; Teneobio: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Sandoz: Consultancy; I-M Consultancy. Diefenbach: LAM Therapeutics: Research Funding; Incyte: Research Funding; Genentech: Consultancy, Research Funding; Trillium: Research Funding; Millenium/Takeda: Research Funding; Seattle Genetics: Consultancy, Research Funding; Merck: Consultancy, Research Funding; MEI: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Denovo: Research Funding. Epperla: Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Feldman: Eisai: Research Funding; Amgen: Research Funding; Cell Medica: Research Funding; Roche: Research Funding; Corvus: Research Funding; Kyowa Hakko Kirin: Research Funding; Pfizer: Research Funding; Trillium: Research Funding; Viracta: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Portola Pharma: Research Funding; Roche: Research Funding. Lossos: Janssen Scientific: Membership on an entity's Board of Directors or advisory committees; NIH: Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Naik: Celgene: Other: Advisory board. Kamdar: Celgene: Consultancy; AstraZeneca: Consultancy; Seattle Genetics: Speakers Bureau; University of Colorado: Employment; Pharmacyclics: Consultancy. Portell: AbbVie: Research Funding; Pharmacyclics: Consultancy; Janssen: Consultancy; Genentech: Consultancy, Research Funding; Bayer: Consultancy; BeiGene: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Acerta/AstraZeneca: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; Roche/Genentech: Research Funding; Infinity: Research Funding; Amgen: Consultancy. Olszewski: Spectrum Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Genentech: Research Funding; Adaptive Biotechnologies: Research Funding. Alderuccio: Agios: Other: Immediate family member; Puma Biotechnology: Other: Immediate family member; Foundation Medicine: Other: Immediate family member; Targeted Oncology: Honoraria; Inovio Pharmaceuticals: Other: Immediate family member; OncLive: Consultancy.XXCopyright

Introduction: Outcomes of patients with classical Hodgkin lymphoma are excellent, and the intent of frontline therapy for even advanced stage disease has been curative. This review summarizes the role of brentuximab vedotin in the upfront treatment of advanced stage classical Hodgkin lymphoma in the context of reducing therapy-related toxicity without compromising the high cure rate. Areas covered: Strategies to reduce bleomycin-induced lung toxicity include a response-adapted approach investigated in the RATHL study and a replacement of bleomycin with brentuximab vedotin in frontline chemotherapy regimens. In both studies, omission of bleomycin in the non-standard arms decreased the rate of pulmonary toxicity while maintaining high progression-free survival and overall survival rates. Expert opinion: The approval of A+AVD in North America offers a new bleomycin-free regimen for the treatment of advanced stage HL, but it must be balanced against a risk-adapted approach. Recently presented subset analyses raise a question about which patients benefit most from this therapy.

An Amendment to this paper has been published and can be accessed via a link at the top of the paper.