The Management of older patients with Hodgkin lymphoma: implications of S1826.

Classical Hodgkin lymphoma (cHL) is diagnosed in patients ages 60 and older in approximately 20%-25% of cases in Western populations. Outcomes in this subset of patients have historically been poor, with 5-year progression free survival (PFS) and overall survival rates significantly lower than those seen in younger patients. Challenges to overcome include age-related co-morbidities, and prominent and potentially lethal treatment-related toxicity. There have been increased efforts to study the older cHL patient population, including analysis of geriatric assessments and the integration of newer targeted therapies such as brentuximab vedotin (BV) and nivolumab (N) into treatment paradigms. A recent phase 3 clinical trial (S1826, NCT03907488) led by the North American oncology cooperative groups compared brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine (BV-AVD) with nivolumab, doxorubicin, vinblastine, and dacarbazine (N-AVD). At a median follow-up of 1-year, N-AVD improved PFS vs BV-AVD in patients and few immune adverse events were observed. Moreover, in a pre-planned subset analyses of cHL patients ages ≥60 years, the 1-year PFS for N-AVD was 93% (95% CI, 79%-98%) versus 64% (95% CI, 45%-77%) for BV-AVD. In addition, N-AVD was largely better tolerated particularly in older patients, which included markedly less neuropathy, lower treatment discontinuation, and less nonrelapse mortality. As a result, N-AVD is poised to become a standard of care for older, advanced-stage cHL patients who are fit for full-dose anthracycline-based combination therapy. More studies are needed to continue to improve outcomes for older cHL patients, especially unfit and frail populations.

Phase II study of the novel antifolate agent pralatrexate in combination with the histone deacetylase inhibitor romidepsin for the treatment of patients with mature T-cell lymphoma.

Previously, we conducted a Phase I study of the combination of pralatrexate and romidepsin in patients with relapsed/refractory (R/R) lymphomas and subsequently conducted a multicenter Phase II study in patients with untreated or R/R mature T cell lymphomas (MTCL). Patients received pralatrexate 25 mg/m2 and romidepsin 12 mg/m2 every 2 weeks. Fourteen patients were evaluable for efficacy. Overall response rate was 35.7% with CR in 14.3% and disease control in 50%. The mDOR was 8.2 months, mPFS was 3.6 months, and mOS was 20.2 months. Gastrointestinal side effects were most common in up to 33%; there was only one hematologic toxicity of grade 3 anemia. Combining results of MTCL patients from the Phase I and II studies (N = 28), the ORR was 53.5% with CR in 21.4%, disease control in67.8%, and DOR of 7.2 months. The combination was safe however does not out-perform other combination strategies.Trial Registration: www.clinicaltrials.gov (NCT01947140).

Hodgkin lymphoma treatment for older persons in the modern era.

There has been a renewed effort globally in the study of older Hodgkin lymphoma (HL) patients, generating a multitude of new data. For prognostication, advancing age, comorbidities, altered functional status, Hispanic ethnicity, and lack of dose intensity (especially without anthracycline) portend inferior survival. Geriatric assessments (GA), including activities of daily living (ADL) and comorbidities, should be objectively measured in all patients. In addition, proactive multidisciplinary medical management is recommended (eg, geriatrics, cardiology, primary care), and pre-phase therapy should be considered for most patients. Treatment for fit older HL patients should be given with curative intent, including anthracyclines, and bleomycin should be minimized (or avoided). Brentuximab vedotin given sequentially before and after doxorubicin, vinblastine, dacarbazine (AVD) chemotherapy for untreated patients is tolerable and effective, and frontline checkpoint inhibitor/AVD platforms are rapidly emerging. Therapy for patients who are unfit or frail, whether due to comorbidities and/or ADL loss, is less clear and should be individualized with consideration of attenuated anthracycline-based therapy versus lower-intensity regimens with inclusion of brentuximab vedotin +/- checkpoint inhibitors. For all patients, there should be clinical vigilance with close monitoring for treatment-related toxicities, including neurotoxicity, cardiopulmonary, and infectious complications. Finally, active surveillance for "postacute" complications 1 to 10 years post therapy, especially cardiac disease, is needed for cured patients. Altogether, therapy for older HL patients should include anthracycline-based therapy in most cases, and novel targeted agents should continue to be integrated into treatment paradigms, with more research needed on how best to utilize GAs for treatment decisions.