Bispecific antibody opens new era of DLBCL treatment

Broadening treatment strategy for relapsed or refractory DLBCL

Expanded indication for 'Columvi'…reduced the risk of death by 41%

The treatment landscape for diffuse large B-cell lymphoma (DLBCL) is changing quickly

The treatment landscape for diffuse large B-cell lymphoma (DLBCL) is changing quickly.

 

Roche's bispecific antibody, which was previously a third-line option, received an expanded indication for second-line treatment, broadening the therapeutic strategy for DLBCL.

 

Given the aggressive nature of DLBCL, where prognosis rapidly worsens after first-line failure, there is significant attention on whether a more potent combination treatment and a new mechanism of action can increase patients' chances of survival.

 

On November 25, Roche Korea held an event at its headquarters in Gangnam-gu, Seoul, to discuss the unmet needs in the DLBCL treatment landscape and the clinical value of its new drug.

 

Roche has already launched products in this field, including Polivy (polatuzumab vedotin) and the bispecific antibody 'Columvi (glofitamab)'.

 

Currently, Polivy can be used as a first-line treatment in combination with cyclophosphamide, doxorubicin, and prednisone (R-CHOP), and Columvi can be used for subsequent lines of treatment.

 

In July, Columvi received an expanded indication from third-line to second-line treatment.

 

The specific indication is for adult patients with relapsed or refractory DLBCL not otherwise specified (DLBCBL NOS) who are ineligible for autologous stem cell transplantation (ASCT), in combination with gemcitabine and oxaliplatin.

 

Professor Seok Jin Kim of the Department of Hematology-Oncology at Samsung Medical Center

Columvi has a 2:1 structure, in which two binding domains target the CD20 surface antigen expressed on malignant B cells, and one domain targets the CD3 antigen expressed on immune T cells.

 

This structure allows for a more robust and stable binding.

 

The efficacy of Columvi was confirmed through the Phase 3 STARGLO study.

 

The trial included patients with relapsed or refractory DLBCL who were ineligible for ASCT after one or more prior systemic therapies, or who had a history of two or more prior systemic therapies.

 

The two-year follow-up results demonstrated that the Columvi + gemcitabine + oxaliplatin combination therapy reduced the risk of death by 41% compared with rituximab + gemcitabine + oxaliplatin combination therapy.

 

The Columvi combination group's Progression-Free Survival (PFS) was 13.8 months, approximately a four-fold increase from 3.6 months in the rituximab combination group.

 

The rate of patients achieving Complete Response (CR) was higher in the Columvi combination group (58.5%) than the control group (25.3%).

 

Professor Seok Jin Kim (President of the Korean Society of Hematology) of the Department of Hematology-Oncology at Samsung Medical Center commented, "While remission can be reached, maintaining it is not easy.

 

Patients in the Columvi combination group survived without disease progression for even one year after the end of treatment.

 

This is a significant finding." Still high unmet needs in DLBCL…"more treatment options must be secured" DLBCL is a disease in which B cells, which protect the body, grow or multiply uncontrollably.

 

It is the most common subtype, accounting for about 40% of Non-Hodgkin Lymphomas.

 

The disease is characterized by its aggressive nature, with rapid progression through stages.

 

The number of DLBCL patients in South Korea was 14,183 as of last year, a 36% increase from 10,428 in 2018.

 

Up to 15% of DLBCL patients fail to respond to the first-line standard treatment, and among those who achieve CR, 25% experience relapse within 18 months.

 

Patients with relapsed/refractory DLBCL face a rapidly deteriorating prognosis as the line of treatment increases.

 

Seunghun Lee, Medical Lead at Roche

Polivy combination therapy is known to be effective in about two-thirds of patients when used as first-line treatment.

 

However, this means that approximately one-third of patients do not benefit from first-line treatment.

 

Chimeric Antigen Receptor T-cell (CAR-T) therapies and bispecific antibodies are now available for subsequent treatment lines.

 

Currently, second-line treatment options include Gilead's CAR-T drug 'Yescarta (axicabtagene ciloleucel)' and the antibody drug Columvi.

 

For the third line, Novartis's ''Kymriah (tisagenlecleucel)' and AbbVie's 'Epkinly (epcoritamab)' are utilized.

 

However, all options except Kymriah are currently non-reimbursed options.

 

Professor Kim stressed, "CAR-T and bispecific antibodies are not to be compared directly.

 

Patients who can tolerate the side effects choose CAR-T, and those who cannot choose the bispecific antibody.

 

If all new drugs were reimbursed, prescribing would align with global guidelines.

 

It is not appropriate to evaluate which drug is superior," pointing out, "The problem is that even when effective treatment options exist, patients are forced to repeat the same treatment due to regulatory approval and reimbursement hurdles." Seunghun Lee, Medical Lead at Roche, said, "The reason the U.S.

 

FDA rejected Columvi for second-line approval was that it did not meet the criteria for the number of enrolled patients, but since it has been approved in major countries in Europe and Asia, we believe the racial differences are not significant," and emphasized, "Roche is currently strengthening its leadership by launching a variety of treatments for hematologic malignancies.

 

We will continue to expand the range of choices in the DLBCL area to enable personalized treatment strategies for different patient groups."