Everolimus Is Active in Pretreated Hodgkin Lymphoma after Failure of Brentuximab Vedotin: Single Institute Experience

Introduction: Patients with Hodgkin lymphoma (HL) relapsing after ASCT and those not eligible for myeloablative therapy can be salvaged with conventional chemotherapy or new novel agents such the immunotoxin brentuximab vedotin and the recently FDA approved anti-PD-1 inhibitor nivolumab. Other options include the mTOR inhibitor everolimus (1) for which, the data in literature is scarce. Moreover, there is no data on the efficacy of everolimus after failure of brentuximab vedotin.

Patients and methods: In this study, we retrospectively analyzed the outcome of patients with relapsed/ refractory HL treated with single agent everolimus at our center between July 2015 and July 2016. All patients were started on everolimus 10 mg daily. Response to treatment was assessed every 2 months. Primary endpoint was the response rate of everolimus as single agent in patients with relapsed/refractory HL.

Results: We identified 5 patients with heavily pretreated HL who received single agent everolimus. Mean age was 24.4 years (range, 20-30). Mean lines of previous treatment was 6.4 (range, 5-8). All patients failed brentuximab vedotin. Two patients failed previous autologous stem cell transplantation. Prior treatments included ABVD, radiation, ICE, ESHAP, miniBEAM, GVD, brentuximab vedotin, gemzar plus brentuximab vedotin, bendamustine, and ASCT.

Mean duration of everolimus treatment was 5 months (range 4-7). One patient showed complete metabolic remission after 5 months of treatment. This remarkable response was achieved after failure of 6 lines. Partial remission and stable disease each were documented in 40%. Grade 1 neutropenia was reported in 80%. Grade 2 anemia, thrombocytopenia, fatigue and stomatitis were observed in 60%, 80%, 20% and 20% respectively. Everolimus dose reduction (5 mg) was required in two cases (one patient had grade 2 thrombocytopenia and other one had grade 3 fatigue). The latter discontinued the treatment after 4 months and is still in complete remission 5 months after discontinuation. No pulmonary toxicity was observed.

Conclusion:The presented data suggest that everolimus is effective in heavily pretreated HL patients who failed conventional treatment including ASCT and new novel agents with 60% ORR. This result is the first of its kind showing efficacy of everolimus after failure of brentuximab vedotin.

Literature:

1. Johnston PB et al. A Phase II trial of the oral mTOR inhibitor everolimus in relapsed Hodgkin lymphoma. Am J Hematol. 2010 May;85(5):320-4.