A phase 1 study of vorinostat maintenance after autologous transplant in high-risk lymphoma

Abstract

Only a minority of patients with high risk lymphoma will be cured with autologous transplant, so maintenance with vorinostat, an oral agent with activity in relapsed lymphoma, was studied starting day + 60 for 21 consecutive days followed by a week off for up to 11 cycles. Twenty-three patients with lymphoma were treated. Ten patients completed the full 11-cycle treatment plan per protocol, four patients were removed due to progressive disease and seven withdrew or were removed from the study due to toxicities. Despite Prevnar vaccine administration every 2 months for three injections, the mean antibody concentration never reached protective levels (> 0.35 μg/mL). Fatigue and functional well-being measured by Brief Fatigue Inventory and Functional Assessment of Cancer Therapy-General improved significantly from cycle 1 to cycle 7, but depression scores from the Center for Epidemiologic Studies Depression scale did not change. Given the toxicities observed, this broad-spectrum deacetylase inhibitor at this schedule is not optimal for prolonged maintenance therapy.

Trial registration: ClinicalTrials.gov NCT00561418.

Keywords: Chemotherapeutic approaches; lymphoma and Hodgkin disease; vaccines.

Figures

Figure 1. The ten most frequent adverse events

The ten most frequent worst grade toxicities experienced per patient, as determined by the Common Terminology Criteria for Adverse Events v3.0 (CTCAE), with attributions of possible, probable and definite in regards to relationship to treatment. A count of each adverse event grade lies within each bar on the graph. There were two DLTs of Grade 3 anorexia, though anorexia was not among the most frequent adverse events experienced.

Figure 2. Prevnar responses

The mean concentration of antibody levels in patients treated with Vorinostat. Patients in this study showed no clinically significant responses for antigens 14 (sample size at each time point ranged from 4 – 9 for each time point measured) and 23 with the clinically relevant threshold of 35 μg/mL.

Figure 3. Overall and progression free survival curves

Progression-free survival and overall survival curves as determined by Kaplan-Meier methods. Hashed lines reflect 95% confidence bounds for the survival distributions. Vertical tick marks reflect censored observations. After a median follow-up of 23.2 months, the median overall and progression free survival have not been reached and the 95% confidence intervals are shown as the hashed lines.