A 73-Year-Old Woman with Relapsed DLBCL - Episode 4
Expert insight on the GO29365 trial, which informs selection of polatuzumab + bendamustine and rituximab in patients with relapsed/refractory DLBCL.
Daniel O. Persky, MD:The seminal study that led to the approval of this regimen by the FDA was a study called GO29365. It was published by [Laurie] Sehn, [MD, MPH,] and colleagues in [the] Journal of Clinical Oncology, in 2020. It was a randomized, phase 2 study, where 40 patients were randomized to BR [bendamustine and rituximab] and 40 were randomized to BR plus polatuzumab. This was 6 cycles with a primary end point being a complete response [CR] rate as assessed by an independent review committee. Secondary efficacy end points included of course such things as duration of response [DoR], progression-free survival [PFS], and overall survival [OS]. The results showed significant advantage of the addition of polatuzumab to BR.
Not only was CR improved from 18% to about 40%, but there were significant and clinically meaningful improvements in DoR, PFS, and OS. The toxicities, generally speaking, were again hematologic. The febrile neutropenia rate and the rates of infection weren’t significantly different. Polatuzumab, of course, did cause a greater degree of neuropathy. However, little if any of it were actually grades 3 and 4, and it was managed by dose reductions and discontinuations if necessary. The implication for practice of this trial is significant because this was a very effective regimen that was useful for our patients.
I have used the regimen of polatuzumab with bendamustine and rituximab in my practice several times, and I believe I was one of the first, if not the first, person in the United States to use it commercially. My experience has been generally favorable. It’s been a very effective regimen for my patients. I haven’t seen much neuropathy in my patients. I have noted that in older patients with relapsed/refractory DLBCL [diffuse large B-cell lymphoma], giving bendamustine becomes a little bit harder with the fifth and sixth cycles, and often it requires either a dose hold or a dose reduction in bendamustine. I would say that it’s important to know that in this study, 85% of the patients were actually refractory to their prior line of therapy. This is a regimen that is effective for patients who have refractory disease. This characteristic could be used to distinguish the regimen from some of the other regimens that are approved, where a proportion of patients with refractory disease, which is a single unfavorable factor prognostically, [saw lower efficacy].
This transcript has been edited for clarity.