Latest in Leukemia and Lymphoma: Advancing Treatment in DLBCL

In patients with diffuse large B-cell lymphoma (DLBCL), diagnosis-to-treatment intervals (DTIs) and pretreatment circulating tumor DNA (ctNDA) levels correlate with tumor burden, but ctDNA more objectively measured disease burden, reported OncLive®.

The findings mean ctDNA can be to quantify and mitigate selection bias in prospective DLBCL clinical trials. The study was published in Journal of Clinical Oncology.

The authors noted that a univariate logistic regression model showed ctDNA and International Prognostic Index (IPI) individually predicted for short DTI.

“ctDNA levels predicted short DTI better than the IPI and were independently prognostic of event-free [survival] and overall survival in multivariable models also including the IPI and DTI,” the authors wrote.

Patients with more advanced-stage DLBCL had shorter DTI compared with patients with limited-stage disease, and patients with higher IPI also had shorter DTI. Meanwhile, median ctDNA levels were significantly higher in patients with advanced-stage DLBCL compared with patients with lower median levels of ctDNA.

“Collectively, our data suggest that ctDNA more objectively measures disease burden than DTI and could therefore have immediate utility to quantify potential selection biases in prospective DLBCL clinical trials,” concluded the authors.

Read more about the study on OncLive®.

A phase 2b clinical trial will examine the combination of maveropepimut-S (DPX-Survivac) and pembrolizumab (Keytruda) plus low-dose cyclophosphamide in patients with recurrent/refractory DLBCL. The trial will be a 3-arm, randomized, parallel-group, Simon 2-stage study. One arm will evaluate DPX-Survivac and pembrolizumab with cyclophosphamide, one arm will evaluate DPX-Survivac and pembrolizumab without cyclophosphamide, and the third arm will examine DPX-Survivac as a monotherapy.

Patients eligible for enrollment will have received 2 or more prior lines of systemic therapy and they have to be ineligible for, or have failed, chimeric antigen receptor (CAR) T-cell therapy or autologous stem cell transplant.

Learn more about the treatment regimen and the phase 2b trial at OncLive®.

Finally, Amitkumar Mehta, MD, assistant professor in the Division of Hematology and Oncology at the University of Alabama at Birmingham (UAB), director of the UAB Lymphoma Working Group, and codirector of the Bone Marrow Transplant-Immune Effector Cell Therapies Program at the O’Neal Comprehensive Cancer Center, discussed the safety profile of lisocabtagene maraleucel (liso-cel) and its use in relapsed/refractor large B-cell lymphoma.

Liso-cel is a CAR T-cell therapy that has been approved to treat adult patients with relapsed/refractory large B-cell lymphoma after 2 or more lines of systemic therapy, including DLBCL. Cytokine release syndrome (CRS) and immune effector cell therapy–associated neurotoxicity are specialized adverse effects of CAR T-cell therapies, but according to Mehta, the incidence of CRS is “much lower” than the other 2 CAR T-cell therapies approved in this setting: axicabtagene ciloleucel and tisagenlecleucel.

Cytopenia, neutropenia, anemia, and thrombocytopenia were commonly observed adverse effects, but overall, liso-cell was “well tolerated,” Mehta said.

Typically, these patients have inferior outcomes to subsequent lines of therapy, and the overall response rates are inferior, but CAR T-cell therapies have “moved the science forward.”

“With lisocabtagene maraleucel, the most important [observation] was that it was welltolerated and the toxicity rates were far lower [compared with other CAR T-cell products], and it had significantly higher, or at least comparable, response rates. Overall, this is a very important treatment and approval,” Mehta said.

Read the full interview at OncLive®.