CD19-Directed Antibody-Drug Conjugates for DLBCL

Part 3: Polatuzumab Vedotin Plus Bendamustine and Rituximab Shows Promise in Patients With DLBCL

The efficacy and data for the combination of polatuzumab vedotin plus bendamustine and rituximab for patients with diffuse large B-cell lymphoma show effective outcomes for patients that clinicians can use when discussing treatment options.

During a live virtual event with other physicians, Bijal Shah, MD, MS, reviewed the efficacy and data for the combination of polatuzumab vedotin (Polivy) plus bendamustine (Treanda) and rituximab (Rituxan; pola-BR) for patients with diffuse large B-cell lymphoma (DLBCL). Shah discussed what made this combination effective, but also which adverse events to look out for.

Which data show the most promising efficacy results for pola-BR?

Recently, data have come from a phase 2 trial that evaluated pola-BR [for treatment of R/R DLBCL and R/R follicular lymphoma]. The trial enrolled patients with 1 or more prior lines of therapy, which reflects how R/R is defined in the National Comprehensive Cancer Network guidelines.1 Patients were required to have an ECOG score of 0 to 2 and no significant peripheral neuropathy, [which can be exacerbated by] polatuzumab. Patients also had to be transplant ineligible.2,3

Transplant ineligibility is a common requirement for patients in R/R DLBCL trials, but in practice I often find this difficult to define. Patients with a prior allogeneic transplant, a recent autologous transplant, or a history of transformation from indolent disease [also were excluded from] this study. Patients were randomly allocated to receive pola-BR or BR only; randomization was conducted within strata of R/R DLBCL and R/R follicular lymphoma.

The distribution of patients by disease type was good [n = 40 in each disease group]. Some patients had up to 7 prior lines [of therapy], but approximately half of patients had 2 [or fewer] prior lines. About 25% of patients had a prior transplant, and 37.5% of patients had GCB disease.

What was the response to pola-BR in this setting?

Response rates to pola-BR were like what we saw with lenalidomide/tafasitamab: the ORR in the pola-BR arm was 45%, with the majority being CRs [40%].3 Among patients who received BR alone, the ORR was 20%, including a CR rate of 17.5%.

PFS, based on the [analysis done by the] independent review committee, was 9.5 months in the pola-BR arm [compared with 3.7 months in the] BR-only arm. OS was 12.4 months in the pola-BR group compared with 4.7 months in the BR group. What [was not evaluated in this trial] is the effect of polatuzumab plus rituximab.

If we know that bendamustine is not adding much—at least BR did not show much [of an effect in this trial]—then it is unclear whether we need to include bendamustine as a component of this regimen. We often ask ourselves this question for our patients at Moffitt [Cancer Center].

What adverse events (AEs) were associated with pola-BR?

Adverse events [AEs] associated with pola-BR included, not surprisingly, cytopenias. [Grade 3 or 4] thrombocytopenia occurred in 41% of patients, and neutropenia in approximately 46% of patients. What may [be surprising] is that in the BR-only arm, 33% of patients developed grade 3 or 4 neutropenia and [23% of patients developed grade 3 or 4] thrombocytopenia.

Polatuzumab is certainly driving some of the thrombocytopenia. Lymphopenia [did not occur in the] BR arm, and the absence of lymphopenia is something I see in almost all the patients I’ve treated with BR, [including those with] mantle cell lymphoma and DLBCL.

Febrile neutropenia was not very common in either arm of the cohort. High-grade nausea, strangely, was not seen in the pola-BR or the BR arms, which contrasts with what was seen in the BRIGHT study [NCT00877006].4 In the pola-BR study, fatigue, decreased appetite, and peripheral neuropathy were common, [occurring in 35.9%, 25.6%, and 43.6% of patients, respectively]. Interestingly, high-grade neuropathy was not seen.3

REFRENCES

1. NCCN. Clinical Practice Guidelines in Oncology. B-cell lymphomas, version 4.2021. Accessed June 6, 2021. https://bit.ly/3geoS5N

2. Sehn LH, Kamdar M, Herrera AF. Randomized phase 2 trial of polatuzumab vedotin (pola) with bendamustine and rituximab (BR) in relapsed/refractory (r/r) FL and DLBCL. J Clin Oncol. 2018;36(suppl 15):7507. doi:10.1200/JCO.2018.36.15_suppl.7507

3. Sehn LH, Herrera AF, Flowers CR, et al. Polatuzumab vedotin in relapsed or refractory diffuse large b-cell lymphoma. J Clin Oncol. 2020;38(2):155-165. doi:10.1200/JCO.19.00172

4. Flinn IW, van der Jagt R, Kahl BS, et al. Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 2014;123(19):2944-2952. doi:10.1182/blood-2013-11-531327