Longer term data validate durable responses with tisagenlecleucel

<p class="article-intro">More than 18 months after patients with relapsed or treatment-resistant diffuse large B-cell lymphoma (DLBCL) were treated with a single dose of tisagenlecleucel, high response rates persist, further demonstrating that this therapy is beneficial for many patients who otherwise wouldn’t have a viable option for treatment.</p> <hr /> <p class="article-content"><p>DLBCL is the most common form of lymphoma, accounting for roughly one-third of all non-Hodgkin lymphoma cases. While current treatment options are successful for many people with this disease, primary therapy often fails in about one-third of people with DLBCL, and half of these patients won&rsquo;t be eligible for stem cell transplantation, which is considered the best second-line treatment approach. Such patients would be candidates for a CAR-T-cell therapy.<br /> The single-arm, open-label phase II trial JULIET is among the largest studies to examine a CAR-T-cell therapy exclusively in people with DLBCL. It was conducted at 27 treatment sites spanning 10 countries across North America, Europe, Australia, and Asia. Enrollees had to receive two or more previous treatments with documented disease progression, or failed to respond or were otherwise ineligible for autologous stem cell transplant. A total of 115 patients were successfully infused. Patients ranged in age from 22&ndash;76 years old with a median age of 56.<br /> In this latest follow-up analysis of the trial, 19-month results show the overall response rate was 54 % among 99 patients who were followed for at least three months or discontinued therapy early, with 40 % achieving a complete response and 16 % achieving a partial response. Moreover, 64 % of patients who achieved a complete response earlier in the trial are currently still in remission with no detectable evidence of cancer. Median duration of response and median overall survival in responding patients was not reached. Response rates were consistent across subgroups of patients, including the elderly and those with particularly aggressive lymphoma (double-/triple-hit) or prior stem cell transplantation.<br /> &bdquo;We&rsquo;re seeing that the responses are sustained. There are a significant number of patients who are staying free of disease, and none of the patients in remission have proceeded on to transplantation,‟ said lead study author Richard Thomas Maziarz, MD, of the Oregon Health &amp; Science Knight Cancer Institute, in Portland, Oregon.<br /> Of note, 54 % of patients who initially had a partial response ended up having a complete response, which suggests that the cell product persists viably and remains active in vivo over time, according to Dr. Maziarz.<br /> Consistent with previous reports on safety, most of the severe adverse events were seen shortly after infusion and included drop in mature blood cells (34 % of patients), CRS (23 % of patients), infection (19 % of patients), and neurological events (11 % of patients). There were no deaths that investigators attributed to the therapy.<br /> Patients in the JULIET trial who responded to therapy will continue to be followed. Dr. Maziarz said that as research evolves, the focus will need to be on approaches for optimizing the outcomes of therapy, such as combination therapy with checkpoint inhibitors or other targeted therapy to enhance, maintain, or stimulate their responses.</p> <p><br /><strong>Reference:</strong><br />Maziarz R et al.: Sustained disease control for adult patients with relapsed or refractory diffuse large B-cell lymphoma: An updated analysis of Juliet, a global pivotal phase 2 trial of tisagenlecleucel. ASH Annual Meeting 2018, abstract #1684</p></p>