My Thoughts on 2 Notable PTCL Studies From ASCO 2019

Steven M. Horwitz, MD

Associate Attending Physician
Lymphoma Service
Department of Medicine
Memorial Sloan Kettering Cancer Center
Associate Professor of Medicine
Weill-Cornell Medical Center
New York, New York

Steven M. Horwitz, MD, has disclosed that he has received funds for research support from ADC Therapeutics, Aileron, Celgene, Forty Seven, Infinity/Verastem, Kyowa-Hakko-Kirin, Millennium/Takeda, Seattle Genetics, and Trillium and consulting fees from ADC Therapeutics, Affimed, Aileron, Angimmune, BeiGene, Corvus, Forty Seven, Infinity/Verastem, Innate Pharma, Kura, Kyowa-Hakko-Kirin, Merck, Millennium/Takeda, miRagen, Mundipharma, Portola, Seattle Genetics, and Syros.

View ClinicalThoughts from this Author

Released: July 22, 2019

The results of 2 interesting clinical trials in peripheral T-cell lymphoma (PTCL) were presented in June at the 2019 ASCO annual meeting. In this commentary, I highlight learnings from both studies—one on a transplant comparison and the other on a PD-1–targeted immunotherapy.

Transplant in Newly Diagnosed PTCL: Autologous vs Allogeneic
Schmitz and colleagues presented final results from the Lymphoma Study Association’s Autologous or Allogeneic Transplantation in T-Cell Lymphoma (AATT) randomized clinical trial. This study enrolled 103 eligible patients younger than 60 years of age with newly diagnosed PTCL, including PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, and anaplastic large-cell lymphoma (ALK negative), among other subtypes. The patients were treated with 4 courses of CHOEP-14, and then those with a response or without progression were treated with DHAP and randomized to either allogeneic stem cell transplant (if donor available; preceded by fludarabine, busulfan, and cyclophosphamide) or autologous transplant (preceded by BEAM).

The results suggest that 3-year event-free survival (EFS) was similar in the intention-to-treat population at approximately 40% in each arm (P = .58). In patients who received transplants, the 3-year EFS rate was higher (~ 63%) but again failed to reach statistical significance between arms (P = .430). The OS rate at 3 years for patients who received transplants was 70% with autologous transplant vs 57% with allogeneic transplant (P = .408). A total of 46 patients (45%) achieved a CR or unconfirmed CR and an additional 17 patients had lesser responses or stable disease. Eight subjects in the allogeneic transplant arm died of transplant-related mortality whereas 7 patients in the autologous arm died of lymphoma. Ultimately, these results do not broadly support allogeneic transplant in PTCL in first remission.

The study was hoped to show a significant EFS improvement at 3 years in patients who received allogeneic stem cell transplant (primary endpoint), but ultimately, it was halted due to futility, as 28% of subjects had disease progression prior to transplant, 37% stopped participation before transplant, and 14% of patients in the allogeneic arm (7/49) were without a suitable donor and received autologous transplant instead.

Allogeneic stem cell transplant has never been widely endorsed or practiced as a strategy for PTCL in first remission. The benefits of dose intensity with autologous transplant in first remission are supported to date by phase II studies only; no randomized studies have been performed and the likelihood of benefit in retrospective analyses has been mixed. Allogeneic transplant, due to the significant risk of transplant-related mortality, is generally relegated to the relapsed setting or used only in those histologies where chemotherapy alone or autologous transplant appear unlikely to provide durable benefit, such as adult T-cell leukemia/lymphoma, hepatosplenic T-cell lymphoma, or other aggressive gamma/delta lymphomas. What this study does highlight is the pressing problem in T-cell lymphoma of optimizing frontline therapy to improve remissions.

PD-1 Inhibition in PTCL: Sintilimab
Natural killer (NK)/T-cell lymphoma cells can have high expression of PD-L1 due to upregulation from Epstein-Barr virus infection. Patients with relapsed extranodal NK/T-cell lymphoma have a poor prognosis with a median OS of only approximately 6 months. Results from an earlier study of the immune checkpoint inhibitor pembrolizumab in 7 patients with NK/T-cell lymphoma who had failed multiple regimens showed 5 of 7 patients achieved durable CRs with PD-1 inhibition.

At ASCO 2019, Tao and colleagues presented results from the ORIENT-4, a single-arm phase II study of the PD-1 inhibitor sintilimab (IBI308) in patients with relapsed/refractory extranodal NK/T-cell lymphoma (nasal). In the study, 28 heavily pretreated patients with NK/T-cell lymphoma who had failed asparaginase-based regimens (median: 3 previous lines) and had at least 1 measurable or FDG-avid lesion were treated with single-agent sintilimab 200 mg every 3 weeks. A total of 19 patients responded (68%; 2 CRs and 17 PRs), with the majority having ongoing responses at the time of the report (median follow-up: 15 months). Of note, 5 patients who initially experienced pseudoprogression subsequently went on to respond or achieved stable disease. In a subgroup analysis, Epstein-Barr virus negativity, lack of B symptoms, normal lactate dehydrogenase, and no bone marrow involvement were associated with better ORRs. Median OS was not reached, with a 1-year OS rate of 82.1%. The most common adverse events were decreased lymphocytes, fever, leukocytopenia, hypothyroidism, pseudoprogression, increased thyroid-stimulating hormone, and hyperglycemia, but these were all grade 1/2 with the exception of 2 patients with grade 3 decreased lymphocyte count.

This prospective study offers an important confirmation of the initial very small study reporting on the utility of PD-1 checkpoint inhibition in patients with NK/T-cell lymphoma. Sintilimab appears active and well tolerated in this challenging setting and invites further study regarding its potential as a treatment option for these patients.

Your Thoughts?
For a discussion of the latest data from the ECHELON-2 trial of brentuximab vedotin in frontline PTCL, click here. What are your most pressing questions about PTCL therapy today? Join the conversation by leaving a question or comment below.

Provided by Clinical Care Options, LLC

Clinical Care Options, LLC
12001 Sunrise Valley Drive
Suite 300
Reston, VA

Sophia Kelley

Supported by an educational grant from
Seattle Genetics

Leaving the CCO site

You are now leaving the CCO site. The new destination site may have different terms of use and privacy policy.


Welcome to the CCO site.

You are accessing CCO's educational content today as a Guest user.

If you would like to continue with free, full access to the CCO Web sites, including free CME/CE credits, please click the button below.


More info

CCO’s educational programs are available completely free of charge on the,, and Web sites. Certain features and functions are restricted for Guest users. By consenting to become a full member, you are eligible to receive CME/CE credit or participation certificates from certified activities, to register for CCO’s free live meetings and webinars, and to receive CCO’s email newsletters alerting you to new content. You can unsubscribe from our emails at any time. CCO strictly protects the privacy of our members, according to our privacy policy.

A confirmation email will be sent to . Not You?