DLBCL Management With Combination Therapy in the Relapsed/Refractory Setting
Ian W. Flinn, MD, PhD, discusses what factors go into his decision to use polatuzumab plus bendamustine and rituximab in certain patients with relapsed/refractory diffuse large B-cell lymphoma.
Ian W. Flinn, MD, PhD, director of lymphoma research at the Sarah Cannon Research Institute, discusses how he decides when to use the combination of the antibody-drug conjugate polatuzumab vedotin-piiq (Polivy) plus bendamustine and rituximab (Rituxan; pola-BR) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL).
The basis of his decision comes from the results of a phase 2 trial (NCT02257567) that looked at 80 patients, randomized 1:1, receiving either 1.8 mg/kg of polatuzumab every 3 weeks plus BR for 6 cycles, or only BR. The primary end point of complete remission (CR) was met with a CR rate of 40% in the pola-BR arm compared with 17.5% in the BR-alone arm.
Moreover, at a median follow-up of 22.3 months, patients on the combination therapy had a median progression-free survival of 9.5 months vs 3.7 months in the B-alone arm (HR, 0.36; 95% CI, 0.21-0.63; P < .001). Survival benefit for patients with pola-BR continued to be demonstrated with a median overall survival of 12.4 months with polatuzumab compared with 4.7 months in the patients just on BR (HR, 0.42; 95% CI, 0.24-0.75; P = .002).
In a previous interview with Targeted OncolgoyTM, Flinn previously discussed these impressive results for patients with a median of 2 prior lines of therapy but does caution that factoring in the patient’s willingness to handle adverse events should be considered. Moreover, he highlights which patients he typically recommends pola-BR for and when to consider other therapies, such as tafasitamab (Monjuvi) in combination with lenalidomide (Revlimid), or loncastuximab (Zynlonta), in this patient population.
0:07 | I use [pola-BR] in patients who have more aggressive disease, so those patients who need a quicker response, who have bulky disease, as they are the patients that are most likely to use this regimen. [Now,] there are other options. For instance, you can think about [using] other approved agents such as loncastuximab, [which is] a reasonable option. Another reasonable option is lenalidomide and tafasitamab. They are largely immunological based therapies, [and] I tend to use those regimens in patients that perhaps are primary refractory or don't have as aggressive disease. For those patients that you need a quick response in, then I tend to use the antibody-drug conjugate with [BR].
1:02 | One other thing to think about is, you want to be careful about using an anti-CD19 therapy in patients [for whom] ultimately the goal is to take them to CAR-T cells, because you might downregulate CD19 and make a CAR T-cell ineffective. On the other hand, you want to avoid bendamustine in patients who prior to harvesting of T cells, as bendamustine is a very lympholytic agent and significantly decreases the number of T cells, [because it] might make it difficult for a patient to go on to receive CAR T cells.