Sequential Brentuxiamb Vedotin For Hodgkin Lymphoma in the Elderly

Outcomes of patients with advanced Hodgkin lymphoma over the age of 60 tend to be inferior compared to younger patients.  One major challenge in treating this patient population is their generally poor health and inability to tolerate toxic chemotherapy regimens. Single-agent therapy with antibody-drug conjugate brentuximab vedotin (BV) has been shown to be an effective first-line treatment for elderly patients who are ineligible for standard treatment regimens, though relapse rates are high and better treatment regimens for this population are needed.

A multicenter phase II trial evaluated the tolerability and efficacy of a modified first-line treatment regimen of BV given sequentially before and after chemotherapy with doxorubicin, vinblastine, and dacarbazine (AVD) in 48 untreated patients aged 60 to 88 years with Hodgkin lymphoma. Patients received two lead-in doses of BV 1.8 mg/kg, followed by six cycles of AVD chemotherapy. Responding patients received an additional four doses of BV consolidation.

A total of 52% of patients were able to complete the entire treatment regimen (induction, chemotherapy, and consolidation), with 73% completing chemotherapy and receiving at least one dose of BV consolidation. Among the first 22 evaluable patients receiving the initial BV lead-in doses, the overall response rate (ORR) was 82%, with 36% of patients achieving complete response (CR). In the 42 patients who completed BV lead in and 6 cycles of AVD, these numbers increased to 95% (ORR) and 90% (CR). In the intention-to-treat population, the 2-year rates of PFS were 84%, and 2-year OS was 93%. Among patients with a Cumulative Illness Rating Scale-Geriatric comorbidity score (CIRS-G) of ≤10, 2-year PFS was 45%, compared to 100% in patients with a score of >10 (P<.001). Baseline loss on instrumental activities of daily living (IADL) was associated with decreased PFS, compared to patients who did not have baseline loss (25% vs 94%; P<.001).

Grade 3/4 adverse events (AEs) occurred in 42% of patients, with neutropenia (44%), febrile neutropenia (8%), pneumonia (8%), and diarrhea (6%) as the most common grade 3/4 AEs. Forty-percent of patients received G-CSF prophylaxis during treatment (mainly during AVD), 15% as primary prophylaxis, and 25% as secondary prophylaxis. Grade 2 peripheral neuropathy, a known complication of BV, occurred in 27% of patients, the majority of which were reversible to grade 1 or lower following treatment completion. Of note, the frequency of grade 3 neuropathy was minimal (4%), which is favorable compared to other studies with BV in the elderly, where grade 3 neuropathy occurs in up to 30% of patients. There was one treatment-related death due to pancreatitis, occurring during BV induction.

The investigators concluded that the sequential BV-AVD regimen was well tolerated and yielded the best reported outcomes to date for untreated elderly patients with Hodgkin lymphoma. Furthermore, this study provides important information regarding prognosis based on geriatric assessment. They highlighted that future investigations should be focused on maintaining these outcomes with less treatment (in particular chemotherapy) and with integration of novel agents such as immune checkpoint inhibitors.

J Clin Oncol. 2018 Sept 4 [Epub ahead of print].

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