Diffuse large B-cell lymphoma (DLBCL) has been known to lack new treatment options besides rituximab (MabThera) for over 20 years.

Approximately one-third of DLBCL patients who undergo existing treatments (primarily R-CHOP) experience relapse or become non-responsive, and the second-line treatment has been limited to intensive chemotherapy and autologous stem cell transplant.

However, the treatment paradigm is changing as innovative treatments, including antibody-drug conjugate (ADC), bi-specific antibodies, and CAR-T cell therapies, have emerged recently.

During the meeting with DailyPharm, Professor Gareth Gregory of Monash University in Australia emphasized the role of treatments with new mechanisms, such as Polivy and Columvi, for older adults or patients who failed previous therapies.

DLBCL still lacks treatments for older adults or transplant-ineligible patients…second-line treatment alternatives are needed

According to Professor Gregory, the highest unmet needs for DLBCL are the second-line treatment.

Exiting treatment data show that approximately one-third of all patients with DLBCL experience disease progression despite undergoing first-line treatments. To date, treatment options have been limited to intensive chemotherapy and autologous stem cell transplant.

Professor Gregory said, "A significant proportion of DLBCL patients globally are elderly, aged 68 or older, and often have comorbidities, thus most of them are ineligible for autologous stem cell transplant," and added, "Given the high relapse rate characteristic of lymphoma, the response rate for patients receiving CAR-T or autologous stem cell transplant treatment in the second line is only about 21%, highlighting a significant need for more effective and safer therapeutic options."

For this reason, interest has grown in treatments with new mechanisms, like bispecific antibodies. The need for monotherapy or combination therapy options, particularly for elderly patients or those who have failed previous treatments, is persistently being raised.

Among the therapies currently driving a paradigm shift in DLBCL treatment are Polivy (polatuzumab vedotin) and the combination therapy of the bispecific antibody Columvi (glofitamab) with Gemcitabine and Oxaliplatin (GemOx).

Particularly in the first-line setting, Polivy in combination with R-CHP is emerging as the new standard of care, replacing the traditional R-CHOP. For relapsed/refractory patients, the combination of the bispecific antibody Columvi and GemOx is gaining attention as a powerful alternative that shows long-term efficacy.

Regarding this, Professor Gregory emphasized that the core of DLBCL treatment is not the 'effectiveness of a single agent,' but the 'design of the entire treatment journey.'

For example, this involves a strategy in which Polivy reduces the risk of relapse in the first line, and Columvi increases the complete response rate in the second-line treatment setting, thereby extending treatment continuity.

Professor Gregory said, "Polivy reduces the risk of relapse and death in first-line treatment, and Columvi offers the potential for long-term survival for relapsed patients," and added, "Both treatments are evolving to improve the patient's entire treatment journey."

Polivy drives changes to the first-line setting...increased expectation of expanded reimbursement

Polivy is evaluated as a key therapy for reducing the risk of recurrence associated with the conventional R-CHOPregimen and for improving long-term patient survival. Fortunately, it recently passed the Cancer Disease Review Committee (CDRC) in Korea, raising expectations for expanded reimbursement for first-line treatment.

The 5-year follow-up data from the POLARIX study showed that the Polivy + R-CHP combination therapy improved both progression-free survival (PFS) and overall survival (OS) compared with conventional R-CHOP, and the rate of transition to subsequent treatments was significantly lower.

Professor Gregory said, "Polivy combination therapy has been included in the first-line recommendations in guidelines in multiple countries, including Australia," and added, "Tolerability was similar to or better than R-CHOP, and we confirmed a long-term trend of reduced risk of relapse and death."

Furthermore, Professor Gregory also pointed out that, given the characteristic of DLBCL, where the risk of relapse increases sharply if complete response is not achieved in the first line, the Polivy combination therapy is significant for its role in reducing treatment burden and medical resource consumption.

He said, "Polivy combination therapy is significant not only for its treatment results but also for the efficiency of medical resources," and added, "Reducing relapse shortens the complex treatment process that leads to high-intensity therapies, and can also reduce patient hospitalization time, medical costs, and the loss of social productivity."

Columvi offers long-term survival potential for relapsed patients...reimbursement remains a hurdle

Meanwhile, in the second-line setting, Columvi is showing new possibilities. Columvi, a bispecific antibody, targets T cells and B cells simultaneously, achieving a high response rate even in relapsed/refractory patients with reduced chemotherapy response.

In the 2-year follow-up analysis of the STARGLO Phase 3 trial, the Columvi + GemOx combination group had a 4-fold increase in PFS (13.8 months vs. 3.6 months) and a more than 2-fold improvement in complete response rate (58%) compared with the rituximab + GemOx group.

Notably, 82% of patients who achieved remission maintained their response for at least 1 year, demonstrating the potential for long-term survival despite the fixed duration of therapy.

Columvi's step-up dosing strategy is highlighted as a clinical feature that secures safety by minimizing immune-related side effects.

Professor Gregory said, "Bispecific antibodies carry the risk of Cytokine Release Syndrome (CRS) due to immune system activation, but Columvi can be managed safely through step-up dosing and pre-treatment," and emphasized, "Columvi has the biggest advantage in that it is an 'off-the-shelf' therapy, meaning it can be administered immediately after diagnosis."

He assessed, "Some patients in the STARGLO trial have maintained a long-term response for over four years, and for patients ineligible for CAR-T or transplant, the Columvi combination therapy offers a possibility of cure."

Despite these therapeutic effects, the issue of utilization in Korea remains a reimbursement barrier.

Polivy was stuck in a non-reimbursed state for five years after its 2020 approval, and Columvi also failed to pass the CDRC in December last year.

Although Polivy initiated its first step toward reimbursement this year with discussions for first-line coverage, Columvi is still waiting for reimbursement listing for its second-line indication.

Professor Gregory mentioned, "Effective treatment is meaningless if it is not delivered to the patient," and added, "Drugs with better accessibility and tolerability should realistically be reimbursed, especially compared to high-cost therapies like CAR-T, which are restricted to limited facilities."

According to Professor Gregory, Australia has already approved reimbursement for the combination therapy of Columvi + GemOx for autologous stem cell transplant-ineligible patients, using the same criteria as those used in the clinical trial patient population.

Finally, he said, "The ultimate goal of lymphoma treatment is to create patient-centered outcomes. If a treatment has sufficient accumulated clinical data, it should be applied to the field quickly," and added, "Institutional support is needed so that patients can receive the best care more safely and rapidly."