25/05/2026
Clinical Evidence for Epkinly in Relapsed/Reractory DLBCL
Dr Daryl Tan
Mount Elizabeth Novena Hospital, Singapore
The treatment landscape for relapsed/refractory diffuse large B-cell lymphoma (DLBCL) continues to evolve rapidly, with increasing movement away from conventional salvage chemotherapy towards earlier integration of CAR T-cell therapy and bispecific antibodies.
In a highly practical and data-rich scientific discussion, Dr Daryl Tan reviewed the persistent limitations of frontline therapy, noting that approximately one-third of patients still fail R-CHOP, with most relapses occurring within the first year. Even with pola-R-CHP, around 30% of patients with IPI ≥2 continue to relapse. POLARIX demonstrated an approximate 6–7% improvement in cure rates in high-risk patients, while Asian subgroup analyses showed clearer separation of PFS and OS curves, potentially reflecting the higher prevalence of ABC-type DLBCL in Asian populations.
The session strongly emphasised upfront identification of biologically and clinically high-risk disease, including ABC-type DLBCL, double-expressor lymphoma, double-hit lymphoma, high IPI, extranodal disease, frailty, and concurrent CNS involvement. CNS disease was repeatedly highlighted as a major adverse feature requiring urgent intervention before irreversible neurological decline.
A memorable case discussion involved a 35-year-old patient with ABC-type DLBCL, MYC rearrangement, MYC/BCL2 double-expressor biology, Ki-67 of 90%, extensive extranodal and marrow involvement, renal impairment, and leptomeningeal CNS disease. Despite frontline pola-R-CHP and intensive intrathecal therapy, the patient deteriorated rapidly with cranial nerve palsy, aspiration pneumonia, ICU admission, and acute kidney injury. Following failure of polatuzumab, rituximab, and lenalidomide, third-line epcoritamab produced rapid neurological recovery and PET-confirmed complete remission after two cycles, with sustained remission maintained one year later.
The historical prognosis of primary refractory DLBCL remains extremely poor. SCHOLAR-1 reported median overall survival of less than six months, with chemotherapy response rates below 6% and complete responses rarely achieved. In contrast, second-line CAR T-cell studies including ZUMA-7 and TRANSFORM demonstrated clear superiority over salvage chemotherapy and autologous transplant in early relapse, with long-term survival plateaus approaching 40%.
Bispecific antibodies are now emerging as a major therapeutic platform in R/R DLBCL. Single-agent glofitamab and epcoritamab achieve ORR of approximately 50–60% with CR rates around 40% in clinical trials, although real-world CR rates may be lower at approximately 20%. Importantly, the discussion repeatedly stressed that complete remission — rather than partial response — is the critical determinant of durable survival.
During the subsequent expert discussion and audience interaction, emerging combination approaches involving bispecific antibodies were also explored, including ongoing experiences and early-phase studies combining bispecifics with GemOx or lenalidomide-based platforms. These discussions reflected growing interest in moving bispecific therapies earlier into the treatment algorithm, particularly in patients unsuitable for transplant or CAR T-cell therapy, although several approaches discussed remain investigational or are not currently approved in routine practice.
A recurring biological principle throughout the session was the importance of T-cell fitness. Because bispecific antibodies rely on endogenous T-cell activity, repeated chemotherapy exposure may reduce effectiveness through T-cell exhaustion. The discussion therefore reinforced the importance of timely escalation before prolonged treatment exposure and physiological decline.
The session also addressed practical Asia-Pacific challenges including reimbursement barriers, outpatient feasibility, ICANS and CRS monitoring, bendamustine exposure prior to CAR T-cell collection, CD20 reassessment at relapse, and the continuing role of autologous stem cell transplantation in late relapse. While CAR T-cell therapy remains highly effective, rapidly progressive patients may not survive long enough for manufacturing timelines, making immediately available bispecific therapy increasingly relevant in urgent disease settings.
Overall, the session reflected a major strategic shift in DLBCL management: earlier recognition of high-risk biology, faster escalation before physiological decline, and increasing integration of bispecific antibodies alongside CAR T-cell therapy and transplantation to maximise the likelihood of complete remission and durable survival.
Disclaimer: The views and reflections above represent personal academic interpretation and discussion points arising from the session. Any mention of investigational or off-label approaches reflects scientific exchange during expert discussion and should not be interpreted as promotional recommendation or formal prescribing guidance. The event organised by AbbVie was conducted as a scientific educational discussion forum intended for healthcare professionals.
