At the 65th American Society of Hematology (ASH) Annual Meeting, Martin Hutchings, MD, PhD, Rigshospitalet, Copenhagen, Denmark, discussed updated data from a phase 1b/2 study which found that the combination of glofitamab plus polatuzumab vedotin yielded high response rates, durable responses, and manageable safety among heavily pretreated patients with diffuse large B-cell lymphoma (DLBCL), including among patients high-grade B-cell lymphoma (HGBCL), and among those with prior chimeric antigen receptor (CAR) T-cell therapy. 

Transcript:

Hello, my name is Martin Hutchings. I am a senior consultant at the Department of Hematology and the phase 1 unit at the Rigshospitalet in Copenhagen Denmark and the professor of Hematology at the University of Copenhagen.

I'm here at ASH, the annual meeting in 2023 in early December in San Diego where the weather is beautiful. I'm presenting today a poster which is an update of the results from an ongoing phase 1b/2 study of the combination of glofitamab with polatuzumab vedotin in patients with relapsed or refractory large B-cell lymphomas.

Glofitamab is a bispecific antibody targeting CD3 on the T-cells and CD20 on the malignant B-cells. It is approved as a single agent in the same indication as the patients who are treated in this study, so relapsed/refractory large B-cell lymphoma. It's given together with polatuzumab vedotin, which is also an approved agent in the same space, but not as a single agent. It's approved to be given together with chemotherapy in the first line or later lines of treatment. These 2 drugs together work well hand in hand because they have very different toxicity profiles so they can be easily combined without synergistic toxicity.

[So far,] 125 patients have been included in the study and [an] unusually large amount of these patients have been of the very difficult to treat histology high-grade B-cell lymphomas, and that's because the study only included that histology for several months in order to enrich that population. Approximately 1/3 of the patients [have] high-grade B-cell lymphomas.

Nevertheless, what we see with this combination of the 2 drugs where glofitamab is given for 12 cycles maximum and polatuzumab for the first 6 cycles maximum, [are] response rates that are way beyond what you would expect to see with single-agent glofitamab. Despite the enriched population with a lot of very difficult-to-treat patients, we have overall responses in approximately 80% of patients, including approximately 60% with complete responses. That should be compared to 52 overall response and 40% complete responses in the study of glofitamab monotherapy, so quite high response rates. Apparently, the combination deepens the already quite substantial response of glofitamab.

What about the high-grade lymphoma patients? Well, what we see is that the response rate in that population may be not quite so high. The overall response is seen in 73%, with complete responses in 57%, but it's still relatively close to the overall population. Even in that difficult setting, [there are] very deep and frequent responses.

What about the durability? Those patients who managed to get into complete response, which again is the majority of patients, generally have very durable responses. Even though the follow-up is limited, we do have enough follow-up to say that approximately 2/3 of patients have duration of complete response, which is 2 years... sorry, 18 months or more. This is aggressive lymphoma patients, so if you fail a treatment which is given for a fixed duration of time, we expect to see disease bounce back relatively quickly, so within the first 1 or 2 years. Durable responses of that length really are to some extent, suggestive of cure.

When we look at the long-term progression or survival curves, what we see in the patients with complete responses is an apparent plateauing of around 40%. It appears, at least at this point in time, that approximately 40% of the patients who managed to get to a [complete response] (CR) are eventually cured.

Source:

Hutchings M, Avigdor A, Sureda Balari AM, et al. Glofitamab Plus Polatuzumab Vedotin Continues to Demonstrate Frequent and Durable Responses and Has a Manageable Safety Profile in Patients with ≥2L Relapsed/Refractory DLBCL, Including HGBCL, and in Patients with Prior CAR T-Cell Therapy: Updated Results from a Phase Ib/II Study. Presented at the 2023 ASH Annual Meeting: December 9-12, 2023. San Diego, CA. Abstract 4460