Bello, Celeste

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Hodgkin lymphoma provide expert, multidisciplinary recommendations for the diagnosis and treatment of Hodgkin lymphoma. The panel convenes annually to update recommendations based on a review of recently published clinical trials. This selection from the NCCN Guidelines for Hodgkin Lymphoma focuses on the management of newly diagnosed and relapsed/refractory classic Hodgkin lymphoma in adults aged 18 to 60 years.

Abstract There are limited data assessing the risk scores for primary treatment failure (PTF) in patients with classical Hodgkin lymphoma (cHL; PTF-cHL) undergoing autologous hematopoietic cell transplantation (auto-HCT). ECLIPSE (Evaluation of Classical Hodgkin Lymphoma patients wIth Primary treatment failure and analySis of outcomEs) is a multicenter retrospective cohort of patients with PTF-cHL (aged ≥15 years) diagnosed on or after 1 January 2005, at 15 US medical centers. PTF was defined as 1 of the following patterns of failure: (1) progressive disease by imaging during or within 6 weeks of completion of frontline chemotherapy (primary progression [PP]); (2) partial response (PR) or stable disease (SD) by imaging after completion of frontline treatment (PR/SD); (3) progression of disease by imaging (and confirmed by biopsy) within 12 months of frontline therapy completion after prior documentation of complete response (CR; early relapse [ER]). A total of 478 patients were included in the analysis. Among these, 217 (45%) were PP, 86 (18%) were PR/SD, and 175 (37%) were ER. The 6-month and 1-year cumulative incidence of nonrelapse mortality after auto-HCT were 0.9% and 1.1%, respectively. The median progression-free survival (PFS) and overall survival (OS) after auto-HCT were 4.33 and 10.09 years, respectively. Although those not in CR at the time of auto-HCT were associated with inferior PFS and OS, advanced age and diagnosis before 2011 were associated with inferior OS. This study showcases the safety and long-term efficacy of auto-HCT, even in patients with high-risk disease who are traditionally considered chemotherapy refractory, and will serve as a benchmark for the ongoing transplant vs no transplant trials.

Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. Classical HL (cHL) and nodular lymphocyte–predominant HL are the 2 main types of HL. The cure rates for HL have increased so markedly with the advent of modern treatment options that overriding treatment considerations often relate to long-term toxicity. These NCCN Guidelines Insights discuss the recent updates to the NCCN Guidelines for HL focusing on (1) radiation therapy dose constraints in the management of patients with HL, and (2) the management of advanced-stage and relapsed or refractory cHL.

The NCCN Clinical Practice Guidelines in Oncology for Hodgkin Lymphoma (HL) provide recommendations for the management of adult patients with HL. The NCCN panel meets at least annually to review comments from reviewers within their institutions, examine relevant data, and reevaluate and update their recommendations. Current management of classic HL involves initial treatment with chemotherapy alone or combined modality therapy followed by restaging with PET/CT to assess treatment response. Overall, the introduction of less toxic and more effective regimens has significantly advanced HL cure rates. This portion of the NCCN Guidelines focuses on the management of classic HL.

Abstract Background: New targeted therapies continue to show improved efficacy in various stages of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), sparing patients from chemoimmunotherapy. However, cure remains elusive. Here, we present a front-line alternative based on a combination of high-dose methylprednisolone (HDMP) and ofatumumab, followed by consolidative therapy with lenalidomide plus ofatumumab. Methods: This is a phase II, single-center study in patients with treatment-naive (TN) CLL/SLL. During the first treatment phase (cycles 1-3) patients received HDMP 1000 mg/m2 IV and ofatumumab 2000 mg (300 mg given week 1 then 2000 mg for a total of 12 doses) IV infusions weekly x 4 doses in cycle 1 of a 28 day cycle, then every 2 weeks for cycles 2 and 3. During the second treatment phase (cycles 4-12), patients received renally adjusted lenalidomide 5-10 mg daily and ofatumumab 2000mg IV once every 8 weeks. Growth factor support was permitted at the discretion of treating physician. Prophylactic medications included allopurinol for tumor lysis syndrome (TLS) 3 days before C1D1 through C1; and trimethoprim/sulfamethoxazole and fluconazole through cycle 4, and acyclovir through C12. Patients received aspirin 81 mg/day as thrombosis prophylaxis while on lenalidomide. Patients were assessed for response by iwCLL 2008 criteria (including imaging assessment) after completion of cycles 3 and 12. The study allowed continuation of lenalidomide if patients achieved complete (CR), partial (PR) response or stable disease (SD). Primary endpoints were efficacy, adverse events (AEs) profile, and time-to-treatment failure (TTF). Results: Between January 2012 and September 2015, the study enrolled a total of 45 patients. Median follow-up was 50.4 (5.6-72.8) months. The median age was 62.6 (48.2-86.1) years. Chromosomal analysis by FISH demonstrated Del17p in 8 (17.8%), Del11q (+/- others, except Del17p) in 10 (22.2%), Trisomy 12 (+/- others, except Del17p and Del11q) in 8 (17.8%), Del13q in 10 (22.2%), no mutations in 9 (20%) patients. The IGHV status was unmutated in 34 (75.6%) cases. Indications to start treatment were: symptomatic lymphadenopathy, symptomatic splenomegaly, anemia, and thrombocytopenia in 5 (11.1%), 10 (22.2%), 12 (26.7%), and 18 (40%), respectively. The median duration of treatment was 35.6 (2.7-66.9) months. Reasons for treatment discontinuation were: progressive disease (PD) in 9 (20%), AEs in 15 (33.3%), transplantation in 3 (6.7%), consent withdrawal in 1 (2.2%), and secondary malignancies in 2 (4.4%) cases. The overall response rates (PR+CR) at 3, 12, 24, 36, and 48 months were 75.6%, 77.8%, 66.7%, 44.4%, and 37.8%, respectively. The CR rates at 3, 12, 24, 36, and 48 months were 2.2%, 11.1%, 20%, 17.8%, and 13.3% respectively. Fifteen patients remain in PR/CR and on treatment at the time of this analysis. The intention-to-treat median TTF was 45.2 (2.9-69.7) months, and was not different among high risk groups such as Del17p, Del11q and/or unmutated IgHV. In patients who discontinued for reasons other than PD the median duration of response without treatment was 30.7 (9.8-69.7) months. Three (6.7%) patients underwent allogeneic hematopoietic cell transplantation after a median of 3 (3 - 4) treatment cycles. Treatment was well tolerated with grade 3/4 infusion reaction in 1 (2.2%) patient. Grade 3/4 treatment-related hematological AEs were neutropenia, thrombocytopenia, and anemia in 33 (73.3%), 5 (11.1%), and 1 (2.2%), respectively. Grade 3/4 infections occurred in 6 (13.3%) patients. No grade 3/4 tumor flares were observed, and there were no cases of TLS or thrombosis. Conclusion: The combination of ofatumumab, HDMP and lenalidomide is effective and well tolerated in treatment-naive CLL/SLL, even when poor prognostic features are present. Disclosures Komrokji: Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau. Locke:Novartis Pharmaceuticals: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy; Kite Pharma: Other: Scientific Advisor. Kharfan-Dabaja:Seattle Genetics: Speakers Bureau; Incyte Corp: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau. Sokol:Spectrum Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Mallinckrodt Pharmaceuticals: Consultancy.