Triplet Combination Safe, Effective for Relapsed/Refractory DLBCL

Patients with relapsed/refractory diffuse large B-cell lymphoma treated with a novel combination of polatuzumab vetodin, rituximab and lenalidomide contributed to an improved overall response and complete response, with 82% remaining in remission at the study’s cutoff date.

A novel triplet combination with polatuzumab vedotin (Polivy), rituximab and lenalidomide was safe and effective in patients with relapsed/refractory diffuse large B-cell lymphoma, according to data presented at the 2021 ASCO Annual Meeting.

“In this first report of a triplet combination of polatuzumab, rituximab and lenalidomide, the triplet combination showed notable efficacy in a challenging-to-treat relapsed and refractory diffuse large B-cell lymphoma population,” said Catherine S.M. Diefenbach, MD, associate professor of medicine, translational director of hematology and director of clinical lymphoma at Perlmutter Cancer Center at NYU Langone Health, during the virtual presentation.

In this phase 1b/2 trial, researchers analyzed the safety of this combination in 57 patients (median age, 71 years; 67% men) with relapsed/refractory diffuse large B-cell lymphoma, were ineligible for or failed prior autologous stem cell transplantation and were treated with at least one prior anti-CD20-containing chemo-immunotherapy regimen. Efficacy of the treatment was assessed in 49 patients (median age, 72 years; 63% men).

“The median age was 71, as is typical for this lymphoma, but the age range was from between 28 and 92 years,” Diefenbach said.

Most patients in the safety and efficacy groups (86% and 84%, respectively) had stage 3 to 4 disease, nearly a quarter had two lines of therapy (28% and 27%) and nearly a third had three or more lines of therapy (33% and 31%). In addition, some patients underwent previous CAR T-cell therapy (5% and 6%, respectively) or prior bone marrow transplant (11% and 12%).

At induction, all patients received induction during 6 28-day cycles with 1.8 mg/kg of intravenous polatuzumab vedotin, 375 mg/m2 of intravenous rituximab and either a dose escalation of oral lenalidomide (between 10 mg and 20 mg) or the recommended daily dose of the drug on days 1 through 21. Patients who responded to the treatment at the end of induction received 6 months consolidation of 10 mg of lenalidomide (days 1 through 21, monthly) and 375 mg/m2 of rituximab (day 1 every 2 months).

Primary endpoints for this trial included the safety and tolerability of this triplet combination, in addition to complete response rates at the end of induction as assessed by positron emission tomography (PET) scans. Follow-up was conducted for a median of 9.7 months in the safety population and for 9.5 months in the efficacy population.

In the safety population, 75% of patients experienced grade 3 to 4 adverse events, with the most common including neutropenia (58%), thrombocytopenia (14%) and infections (14%). Adverse events led to 26% of patients undergoing a lenalidomide dose reduction and 67% had treatment interruption. One grade 5 adverse event related to the treatment — neutropenic sepsis — was reported.

“The additional (adverse events) were not considered related to study drug,” Diefenbach said. “For example, a patient who had a fatal gastric hemorrhage who had been enrolled but not yet treated, and a patient with COVID-19 who contracted this disease 167 days after his last dose of the study therapy.”

In the efficacy population, the overall response rate was 39% with a complete response rate of 29%. Ten percent of patients had a partial response. Median progression-free survival for the entire population was 6.3 months (95% CI, 4.5-9.7) with a median duration of remission of 8.1 months (95% CI, 4.7-not evaluated) and a median overall survival of 10.9 months (95% CI, 10.9-not evaluated).

“However, for the patients who obtained a (complete response) — this is 13 patients — who were evaluable, the median progression-free survival at 9 months had not been reached, nor has the median overall survival,” Diefenbach said. “Nearly all patients remain in complete remission.”

“Additional follow-up is needed to assess the impact of consolidation therapy on the duration of long-term response,” Diefenbach said. “In summary, the triplet combination of polatuzumab, rituximab and lenalidomide represents a potential novel regimen for patients with transplant-ineligible relapsed and refractory diffuse large B-cell lymphoma and is worthy of further study.”


Magid Diefenbach CS, Abrisqueta P, Gonzalez-Barca E, et al. Polatuzumab vedotin (Pola) + rituximab (R) + lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Primary analysis of a phase 1b/2 trial. J Clin Oncol. 2021;39(suppl 15):Abstract 7512.