Pembrolizumab, a humanized IgG4 monoclonal antibody targeting programmed death-1 protein, has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma (cHL). To assess the complete metabolic response (CMR) rate and safety of pembrolizumab monotherapy in newly diagnosed cHL, we conducted a multicenter, single-arm, phase II investigator-initiated trial of sequential pembrolizumab and doxorubicin, vinblastine, and dacarbazine (AVD) chemotherapy. Patients > 18 years of age with untreated early unfavorable or advanced stage disease were eligible for treatment. Thirty patients with either early unfavorable (n=12) or advanced (n=18) stage cHL were treated with 3 cycles of pembrolizumab monotherapy followed by AVD for 4-6 cycles depending on stage and bulk. Twelve had either large mediastinal masses and/or bulky disease (>10 cm). Following pembrolizumab monotherapy, 11 patients (37%) demonstrated CMR's, and an additional 7 of 28 (25%) patients with quantifiable positron emission tomography/computed tomography scanning (PET-CT) had >90% reductions in metabolic tumor volume. All patients achieved CMR following 2 cycles of AVD and maintained their responses at end of treatment. With a median follow-up of 22.5 months (range: 14.2-30.6) there have been no changes in therapy, progressions, or deaths. No patients received consolidation radiotherapy, including those with bulky disease. Therapy was well-tolerated. The most common immune-related adverse events were grade 1 rash (n=6), and grade 2 infusion reactions (n=4). One patient had a reversible grade 4 transaminitis and a second had a reversible Bell's palsy. Brief pembrolizumab monotherapy followed by AVD proved both highly effective and safe in newly diagnosed cHL patients including those with bulky disease. This trial was registered at www.clinicaltrials.gov as #NCT03226249.

Laboratory costs of thrombophilia testing exceed an estimated $650 million (in US dollars) annually. Quantifying the prevalence and financial impact of potentially inappropriate testing in the inpatient hospital setting represents an integral component of the effort to reduce healthcare expenditures. We conducted a retrospective analysis of our electronic medical record to evaluate 2 years' worth of inpatient thrombophilia testing measured against preformulated appropriateness criteria. Cost data were obtained from the Centers for Medicare and Medicaid Services 2016 Clinical Laboratory Fee Schedule. Of the 1817 orders analyzed, 777 (42.7%) were potentially inappropriate, with an associated cost of $40,422. The tests most frequently inappropriately ordered were Factor V Leiden, prothrombin gene mutation, protein C and S activity levels, antithrombin activity levels, and the lupus anticoagulant. Potentially inappropriate thrombophilia testing is common and costly. These data demonstrate a need for institution-wide changes in order to reduce unnecessary expenditures and improve patient care.

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We performed a multicenter retrospective analysis across 10 US academic medical centers (2010 - 2018) to evaluate current treatment patterns and outcomes in patients age ≥60 with classical Hodgkin lymphoma (cHL). Among 244 eligible patients, median age was 68, 63% had advanced stage (III/IV), 14% had ECOG performance status (PS) 2-4, and 12% had documented loss of ≥1 activity of daily living (ADLs). Medical comorbidities were assessed by the Cumulative Illness Rating Scale - Geriatric (CIRS-G), where n=44 (18%) had total scores ≥10. Using multivariable Cox models, only ADL loss predicted shorter progression-free (PFS; HR 2.13, p=0.007) and overall survival (OS; HR=2.52, P=0.02). Most patients (n=203, 83%) received conventional chemotherapy regimens, including ABVD (56%), AVD (14%), and AVD with brentuximab vedotin (BV; 9%). Compared to alternative therapies, conventional regimens significantly improved PFS (HR 0.46, P=0.0007) and OS (HR 0.31, p=0.0003). Survival was similar following conventional chemotherapy in those ages 60-69 vs ≥70: PFS HR 0.88, p=0.63; OS HR 0.73, p=0.55. Early treatment discontinuation due to toxicity was more common with CIRS-G ≥10 (28 vs 12%, p=0.016) or documented geriatric syndrome (28 vs 13%, p=0.02). A competing risk analysis demonstrated improved disease-related survival with conventional therapy (HR 0.29, p=0.02) and higher mortality from causes other than disease or treatment in those with high CIRS-G or geriatric syndromes. These data suggest conventional chemotherapy regimens be considered standard of care in fit older patients with cHL, and highlights the importance of geriatric assessments in defining fitness for cHL therapy going forward.