In a recent publication in Lancet Hematology, researchers sought to ascertain if the use of the novel combination of polatuzumab vedotin in conjunction with rituximab and lenalidomide (Pola+R+Len) would deliver a tolerable therapeutic option with enhanced antitumor response in patients diagnosed with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

The authors wrote, “Diffuse large B-cell lymphoma comprises nearly 30% of non-Hodgkin lymphoma cases and patients with relapsed or refractory DLBCL who are ineligible for stem-cell transplantation, have few treatment options and poor prognoses.”

This study was a phase Ib/II, open-label, multicenter, single-arm study conducted at 19 clinical sites in the United States, Spain, and the United Kingdom.

The researchers indicated that the study’s primary objective was to assess the safety and efficacy of the combination of Pola+R+Len in patients with relapsed or refractory DLBCL.

Eligible patients were those ≥18 years old with histologically documented CD20-positive relapsed or refractory DLBCL and Eastern Cooperative Oncology Group performance status of 2 or lower. Other criteria for inclusion included receiving at least one previous line of chemoimmunotherapy, including an anti-CD20 agent, and being ineligible for stem-cell transplantation.

The dose-escalation phase (Ib) utilized escalating doses of lenalidomide to obtain the recommended phase II dose. Patients also received six 28-day cycles of induction treatment with IV rituximab 375 mg/m2 and IV polatuzumab vedotin 1.8 mg/kg (all cohorts) plus oral lenalidomide at the following doses: 10 mg (cohort A), 15 mg (cohort B), and 20 mg (cohort C).

On Day 1, rituximab and polatuzumab vedotin were administered. On Days 1-21 of each 28-day cycle, patients received lenalidomide. During the dose-expansion phase (II), patients received six 28-day cycles of Pola+R+Len at the recommended phase II dose established during dose escalation.

In both phases, patients with a complete response or partial response at the end of induction were eligible for postinduction therapy with rituximab 375 mg/m2 on Day 1, and on Days 1-21 of each 28-day cycle, patients received lenalidomide 10 mg/day for a maximum of six cycles.

The researchers indicated that the primary safety objective of the dose-escalation phase was the detection of the maximum tolerated dose through the incidence of dose-limiting toxic effects, and the primary efficacy outcome of the dose-expansion phase was the Independent Review Committee-evaluated complete response rate at the end of induction, based on PET-CT.

The authors wrote, “Analyses were conducted in the safety population, which included all patients who received at least one dose of any study drug, and the efficacy population, which included all patients who received at least one dose of any study drug at the recommended phase 2 dose.”

Between July 11, 2017, and February 3, 2020, 57 patients were enrolled (average age 71 years [interquartile range (IQR) 60-75]) and comprised of 38 males (67% of the study population) and 19 females (33% of the study population). Moreover, 47 participants (82%) were not Hispanic or Latino, and the median previous lines of therapy was 2 (IQR 1-3). Eighteen participants and 39 patients were included in phase Ib and phase II, respectively.

Data from phase Ib confirmed a 20-mg recommended phase II dose for lenalidomide, and after an average follow-up of 11.8 months (IQR 4.7-25.8), the complete response rate, as evaluated by the Independent Review Committee, was 31% (90% CI, 20-43).

The results also indicated that the most common grade III–IV adverse events were 35 cases (61%) of neutropenia and eight cases (14%) of thrombocytopenia. Additionally, 23 cases (40%) of the 57 patients experienced serious adverse events, and one mortality was reported due to a treatment-related adverse event documented as neutropenic sepsis.

Based on their findings, the authors noted that while the Pola+R+Len combination did not meet the prespecified activity threshold, data revealed that there were some clinical benefits observed in some patients, and this novel regimen was correlated with a tolerable safety profile in patients with relapsed or refractory DLBCL.

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