Latest Advances in Glofitamab for LBCL

Glofitamab (Columvi) is a new bispecific antibody that can be used in both monotherapy and combination regimens. It is particularly effective for relapsed and refractory large B-cell lymphoma and as of December 2024 it was accepted for evaluation by the FDA based on the phase III STARGLO study results that we will cover in this article. 

Glofitamab as Monotherapy

Having a single medication is convenient for many reasons, it can increase quality of life and reduce the risk of having severe side effects. It can be easily monitored and it requires fewer visits to the clinic.  

At the ASH conference, we had the opportunity to interview Dr. Joshua Brody, who shared insights into his research, a 3-year follow-up of patients who took glofitamab as monotherapy. Remarkably, the patients who had undergone multiple therapies in the past could remain in remission with glofitamab only for a long time. 

The latest three-year follow-up of the pivotal Phase II study reinforces glofitamab’s role as an effective, fixed-duration treatment for patients with relapsed or refractory large B-cell lymphoma. 

A Strong Duo: Glofitamab + Polatuzumab Vedotin

This combination accomplishes durable responses in people who have received multiple therapies in the past.

The extended follow-up of the Phase Ib/II study highlights the sustained efficacy and manageable safety of glofitamab in combination with polatuzumab vedotin for patients with relapsed or refractory large B-cell lymphoma, including those with high-grade B-cell lymphoma. 

At the ASH conference, we interviewed the lead investigator and presenter, Dr.  Catherine Diefenbach who shared details of this new combination and its importance. 

With a median follow-up of nearly two years, all patients responded to this treatment and remained in response for over two and a half years. 

The safety profile remained consistent with previous findings, with cytokine release syndrome as the most common adverse event, though primarily low-grade and manageable. These results underscore glofitamab plus polatuzumab vedotin as a promising treatment option for heavily pretreated patients, particularly those with aggressive disease who need effective alternatives.

STARGLO Trial: Glofitamab + GemOx 

The STARGLO trial is relevant because it was conducted at 62 centers in 13 countries in Asia, Australia, Europe, and North America. It involved a total of 274 patients, with 58% male and 42% female.

In this trial, patients received one of these two therapies: 

• 183 patients received glofitamab step-up dosing to 30 mg + Intravenous gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2; for a total of eight cycles, plus four additional cycles of glofitamab monotherapy
• 91 patients received rituximab + intravenous gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 plus rituximab 375 mg/m2; for a total of eight cycles

After a median follow-up of 1 year, the overall survival significantly improved with Glofit-GemOx. However, all patients experienced side effects; for instance, 44% of them had low-grade cytokine release syndrome. 

The FDA has accepted Genentech’s supplemental Biologics License Application (sBLA) for glofitamab-gxbm (Columvi®) in combination with gemcitabine and oxaliplatin (GemOx) for patients with relapsed or refractory diffuse large B-cell lymphoma who cannot undergo autologous stem cell transplantation.

Based on results from the ongoing Phase III STARGLO trial, this combination demonstrated a clinically meaningful improvement in overall survival compared to rituximab ( Rituxan®) plus GemOx, making glofitamab the first CD20xCD3 bispecific antibody to show a survival benefit in a Phase III trial for DLBCL. 

This off-the-shelf, fixed-duration regimen could provide an important treatment alternative for patients at high risk of disease progression, particularly those ineligible for standard high-dose chemotherapy and stem cell transplant. 

The FDA is expected to make a decision on approval by July 20, 2025. Stay tuned toat the HealthTree News Site to see our coverage on this topic. 

Stay Tuned

Bridging Therapy: Glofitamab + RICE 

The Phase Ib trial for transplant- and CAR-T-eligible patients with relapsed or refractory DLBCL used glofitamab in combination with R-ICE (Rituximab+ Ifosfamide, Carboplatin, and Etoposide).

The results showed an estimated overall response rate of 78.1% with manageable side effects, highlighting glofitamab’s potential. This therapy addresses the unmet need for pre-transplant and CAR-T bridging treatments in aggressive DLBCL. Given that standard therapy is not effective in approximately half of DLBCL patients, incorporating glofitamab earlier in the treatment sequence may improve access to curative therapies such as autologous stem cell transplant and CAR-T. 

Bridging Therapy: Glofitamab + RICE 

The Phase Ib trial for transplant- and CAR-T-eligible patients with relapsed or refractory DLBCL used glofitamab in combination with R-ICE (Rituximab+ Ifosfamide, Carboplatin, and Etoposide).

The results showed an estimated overall response rate of 78.1% with manageable side effects, highlighting glofitamab’s potential. This therapy addresses the unmet need for pre-transplant and CAR-T bridging treatments in aggressive DLBCL. Given that standard therapy is not effective in approximately half of DLBCL patients, incorporating glofitamab earlier in the treatment sequence may improve access to curative therapies such as autologous stem cell transplant and CAR-T. 

These findings suggest that glofitamab could reshape treatment strategies for high-risk patients, offering a novel approach to achieving disease control before definitive therapy.

Final Thoughts 

Beyond individual study results, glofitamab's impact lies in its potential to redefine treatment strategies for high-risk and heavily pretreated DLBCL patients. Its fixed-duration regimen and off-the-shelf availability mark an important shift towards more accessible, effective therapies.

As research continues, patient participation in clinical trials remains crucial. Every new study brings us closer to expanding treatment options and improving outcomes for those facing DLBCL. If you or a loved one are considering participating in a clinical trial, we encourage you to explore ongoing research opportunities and stay informed about the latest advancements.

Educated patients have better outcomes, so with HealthTree, you can keep learning more with our free educational webinars, during which lymphoma specialists answer all your questions! 

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Sources: 

• FDA Accepts Genentech’s Columvi Combination for People With Relapsed or Refractory DLBCL 
• Glofitamab plus GemOx versus rituximab-GemOx for relapsed or refractory DLBCL (STARGLO) 
• Fixed-Duration Glofitamab Monotherapy 
• Glofitamab in Combination with Polatuzumab Vedotin 
• Glofitamab in Combination with Rituximab Plus Ifosfamide, Carboplatin, and Etoposide in Relapsed or Refractory DLBCL