Management of Peripheral T-cell Lymphomas and the Role of Transplant.

PURPOSE OF REVIEW: Here, we review the management of peripheral T-cell lymphoma, particularly focusing on the role of autologous and allogeneic stem cell transplant. RECENT FINDINGS: Peripheral T-cell lymphomas are a rare subset of non-Hodgkin's lymphomas that are treated with curative intent. While therapy has been based on other aggressive lymphoid malignancies, outcomes are generally poorer than B-cell lymphomas with 5-year overall and progression-free survival of 30-40% and 20-30%, respectively. In effort to improve outcomes, transplant has been used in both the frontline and salvage settings. Although not studied in randomized studies, consolidation with autologous stem cell transplant in first remission has been associated with an approximate 5-year overall survival of 50-60% and 5-year progression-free survival of 40-45%. Unfortunately, most patients relapse, and, in this setting, allogeneic transplant remains the only curative option for those who are transplant-eligible. Multiple series have now shown that 3-year overall survival with allogeneic transplant is approximately 60%. However, outcomes with transplant are associated with disease control at the time of transplant. In contrast to B-cell malignancies, treatment decisions for peripheral T-cell lymphomas are supported mostly by phase II studies, retrospective series, and expert opinion. For patients with peripheral T-cell lymphoma able to achieve sufficient disease control, autologous stem cell transplantation in first remission and allogeneic stem cell transplantation in relapsed disease offer modest benefit over chemotherapy alone.

SOHO State-of-the-Art Updates and Next Questions: Treatment for Newly Diagnosed Peripheral T-Cell Lymphomas.

Although a rare subset of non-Hodgkin lymphomas, peripheral T-cell lymphomas (PTCL) account for a disproportionate proportion of patient mortality. Conventional therapies are derived from experience treating aggressive B-cell lymphomas and center around CHOP-based chemotherapy. However, due to the unique biology and diverse subtypes of PTCL, most patients fail to durably respond to this approach and 5-year survival is only 20% to 30%. There have been multiple attempts to improve outcomes for patients with PTCL. Among the more successful strategies are the use of consolidative autologous stem cell transplant, the augmentation of CHOP with etoposide (CHOEP), and the use of brentuximab vedotin in CD30-positive PTCL. Advances in the understanding of histology-specific biology has cultivated enthusiasm to evaluate hypomethylating agents, histone deacetylate inhibitors, and phosphoinositol-3-kinase inhibitors in the frontline setting. Improvements in monitoring disease response and prognostication including the use of cell-free DNA, mutational profiling, and interim PET/CT imaging are also on the horizon. For patients with acute T-cell leukemia/lymphoma, the use of mogamulizumab-based therapy in the frontline setting may lead to advances in care. The true impact of these new-era therapies will only be elucidated as clinical practices incorporate the rapidly changing evidence.

Blinatumomab consolidation post-autologous stem cell transplantation in patients with diffuse large B-cell lymphoma.

ABSTRACT: Outcomes in patients with relapsed diffuse large B-cell lymphoma (DLBCL) who undergo autologous stem cell transplant (auto-SCT) are poor. Blinatumomab is a CD3/CD19 bispecific T-cell engager that directs cytotoxic T cells to CD19+ cells. Here, we performed a pilot study of blinatumomab consolidation after auto-SCT for 14 patients with DLBCL or transformed follicular lymphoma. All patients underwent standard-of-care auto-SCT with carmustine, etoposide, cytarabine, and melphalan (BEAM) conditioning followed by 1 cycle (4 weeks continuous infusion) of blinatumomab consolidation starting at day 42 after auto-SCT. All 14 patients treated on study completed BEAM auto-SCT and 1 cycle of posttransplant blinatumomab. Five patients developed grade 1 cytokine release syndrome (CRS), with no grade 2 or higher CRS. Immune effector cell-associated neurotoxicity syndrome was not observed. Patients were followed up for 3 years after auto-SCT, with median follow-up of 37 (range, 12-65) months. One-hundred days after auto-SCT (1 month after blinatumomab consolidation), 12 patients (86%) had achieved complete remission. At 1 year after auto-SCT, 7 patients (50%) remained in CR, and 1 patient had died of progressive disease. Patients who relapsed had a lower CD8:CD4 T-cell ratio before starting blinatumomab than patients who remained in remission. This pilot study demonstrates blinatumomab consolidation after auto-SCT is safe and well tolerated. Strategies to increase the CD8:CD4 ratio and use additional cycles of consolidation in a larger randomized trial are needed to confirm the efficacy of consolidation with blinatumomab after auto-SCT. This trial was registered at www.clinicaltrials.gov as #NCT03072771.

The characteristics, treatment patterns, and outcomes of older adults aged 80 and over with multiple myeloma.

OBJECTIVES: Tremendous progress has been made in the treatment of multiple myeloma; however, the majority of this success has been demonstrated in younger patients. With 36% of patients >80 years-old at diagnosis, it is important to understand if older patients are receiving similar benefits. MATERIALS AND METHODS: We identified 2155 patients diagnosed with myeloma at age 80 or older in the Surveillance, Epidemiology, and End Results Program (SEER)-Medicare database from 2007 to 2013. A cohort of 2933 similar patients diagnosed with myeloma at age 70-79 was used for comparison using a difference-in-differences design. RESULTS: Only 51% of patients >80 years-old at diagnosis received systemic anti-myeloma treatment. Treatment was associated with a 26% decrease in hazard for death, independent of age, race, gender, poverty, comorbidities, and proxy measures of performance status. In the 70-79 cohort, treatment was associated with a 22% decrease in hazard for death. Based on the difference-in-differences design, there is no statistically significant difference in treatment benefit based on age cohort (p = .610). CONCLUSIONS: Anti-myeloma treatment produces a similar survival benefit among the oldest patients. The population over 80, when myeloma incidence peaks, is projected to triple over the next few decades. It is imperative that we continue to advance our understanding of the needs of this vulnerable subgroup of patients with myeloma.