Commentary

Article

City of Hope’s Dr Tycel Phillips Discusses Promise of Glofitamab in Heavily Pretreated MCL

Glofitamab is currently being investigated in a phase 1/2, multicenter, open-label, dose-escalation study as monotherapy and in combination with obinutuzumab, following 1-time fixed-dose pretreatment with obinutuzumab for B-cell non-Hodgkin lymphoma, of which mantle cell lymphoma (MCL) is a rare type.

Glofitamab, a bispecific T-cell engager, is currently being investigated in a phase 1/2, multicenter, open-label, dose-escalation study (NCT03075696) as monotherapy and in combination with obinutuzumab, a humanized anti-CD20 antibody, following 1-time fixed-dose pretreatment with obinutuzumab.1

An interim analysis of this trial was presented today at the 2024 annual meeting of the American Society of Clinical Oncology, by Tycel Phillips, MD, associate professor, Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, in the oral abstract session, “Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia.”

Data in his abstract, “Glofitamab monotherapy in patients with heavily pretreated relapsed/refractory (R/R) mantle cell lymphoma (MCL): updated analysis from a phase I/II study,” show that most patients with heavily pretreated relapsed/refractory MCL, a rare type of B-cell non-Hodgkin lymphoma, with a complete response at the end of therapy were alive and progression free at 15 months after therapy ended.2

Transcript

Can you discuss the importance of these findings for patients with MCL previously refractory to a Bruton tyrosine kinase (BTK) inhibitor?

I think, in the short term, the thing that’s beneficial for patients is that in this post-BTK space, we have very limited options for durability. For the most part, we are shifting from treatment to treatment in a majority of these patients outside of the chimeric antigen receptor therapy [CAR T], brexucabtagene autoleucel. Because glofitamab can be given in a clinical setting—it doesn’t necessarily have to be given in a CAR T or transplant center—it does, in this situation, give some hope that we can have some durability of response, that we’ll have a little bit more greater access to patients and not require them to necessarily uplift or greatly alter their lifestyle, or life, to get a treatment to get some durability of response.

So again, encouraging early findings. We do need more long-term maturation of the clinical data in order to get a true sense of how doable these responses are. But from this, this most recent update is still very encouraging for this patient population, where again, like I said, there are very little treatments available for patients.

What are some advantages of giving patients this fixed-duration treatment?

By having a fixed duration, A, it does allow for some immune recovery; it allows patients the ability to sort of reconstitute the immune system and reduces some of the risk of long-term infections. Also, you would presume that this would reduce the amount of cost to the medical system because, again, the patient isn't coming in for an indefinite period of time with blood draws, vitals, etc, and then not to mention the cost of the medication. So, again, going back to your first question, if these responses remain durable, with the treatment duration only being around 8.3 months, it does allow these patients to get an effective therapy, an efficient therapy, and then again have some time where they're not necessarily being bogged down in a medical system and enjoy some quality of life.

As earlier use of BTK inhibitors becomes more common, is it possible glofitamab outcomes among those refractory to BTK inhibitors will improve?

It's a bit speculative. In theory, we always assume the less pretreated the patients are, the more likely they are to respond to certain therapies. I don't necessarily know if we'll see a major shift in the efficacy based on whether they get more or less lines of therapy. But historically, that has been the case. If you look at the BTK inhibitors as an example, when they first came out, they were using the third-line setting. And then we saw that patients who got those drugs in a second-line setting had a much higher chance of getting a complete response and a durable response. So if that mechanism continues to follow suit with these biopecifics, you will presume that you would get a little bit higher response rate and a little bit more duration of response if it's given earlier. But again, I think we would need to see a little bit of a bigger trial just to get that sort of true sense of how the lines of therapy are impacting efficacy of glofitamab.

References

1. A dose escalation study of glofitamab (RO7082859) as a single agent and in combination with obinutuzumab, administered after a fixed, single pre-treatment dose of obinutuzumab in participants with relapsed/refractory B-cell non-Hodgkin's lymphoma. ClinicalTrials.gov. Updated May 14, 2024. Accessed June 1, 2024. https://clinicaltrials.gov/study/NCT03075696

2. Phillips TJ, Carlo-Stella C, Morschhauser Fanck, et al. Glofitamab monotherapy in patients with heavily pretreated relapsed/refractory (R/R) mantle cell lymphoma (MCL): Updated analysis from a phase I/II study. Presented at: ASCO 2024; May 31-June 4, 2024; Chicago, IL. Abstract 7008. https://meetings.asco.org/2024-asco-annual-meeting/15770

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