When the Treatment That Was Working Stops Working
Hodgkin lymphoma responds well to treatment in most cases. Modern immunotherapy drugs — particularly PD-1 inhibitors — have dramatically improved outcomes, especially for patients who relapse after initial chemotherapy.
But some patients stop responding to PD-1 therapy. And when that happens, the options have been limited.
This is the story of what happens next.
The Immune System's Hidden Escape Route
PD-1 inhibitors work by removing a molecular "off switch" that cancer cells use to hide from immune cells. Removing that switch tells the immune system to attack.
But cancer is adaptable. When the PD-1 switch is blocked, some tumors flip on another one — a protein called TIM-3. It acts like a second lock on the same door. Even when PD-1 is blocked, TIM-3 can still suppress the immune response and allow the tumor to keep growing.
Think of it this way: a thief installs a backup lock after you change your front door deadbolt.
A New Drug That Targets the Backup Lock
TQB2618 is a new antibody designed specifically to block TIM-3. The hypothesis behind the GOING-style combination used in this trial was direct: pair TQB2618 with penpulimab (a PD-1 inhibitor) to block both immune checkpoints at the same time.
By targeting both the primary and the backup lock simultaneously, the hope was that the immune system could finally break through.
Who Was in the Trial
The multicenter Phase Ib trial enrolled 28 patients with relapsed or refractory classical Hodgkin lymphoma at 12 sites in China between 2022 and 2024. All patients in the main expansion phase had previously been treated with PD-1 or PD-L1 inhibitors. Median age was 32 — a reminder that Hodgkin lymphoma disproportionately affects younger adults.
The objective response rate — the proportion of patients whose tumors shrank meaningfully — was 52% among the 21 evaluable Hodgkin lymphoma patients. That included one complete response and ten partial responses.
Treatment-related side effects occurred in 86% of patients, though most were manageable. Grade 3 or higher (serious) side effects affected 24% of patients, with low platelet counts and anemia being the most common.
As of the data cutoff in December 2024, median follow-up was just over 14 months, and median duration of response and overall survival had not yet been reached — meaning responses were ongoing in many patients.
That's Not the Full Story
But here's the catch.
A 52% response rate is meaningful, but this is an early-phase, single-arm trial with no comparison group. We don't know yet how durable the responses will be, or how the combination compares to existing options for the same patient population. The trial was also conducted exclusively in China, and outcomes may vary in other settings.
What the Field Is Watching
Hodgkin lymphoma specialists have been waiting for an approach that meaningfully works after PD-1 failure. The TIM-3 pathway has been a target of interest for several years, but clinical evidence in Hodgkin specifically has been limited. This trial is one of the first to show real-world efficacy in this setting.
The fact that responses were ongoing in many patients at 14 months — without yet reaching a median — suggests durability may be one of this combination's strengths.
If you or someone you know has Hodgkin lymphoma that has relapsed after PD-1 immunotherapy, this research is early but encouraging. The combination is not yet approved or standard, but it may be available through clinical trials. Asking your oncologist about TIM-3 targeting approaches and whether any trials are recruiting in your area is a reasonable next step.
This is a Phase Ib trial result — it establishes safety and early efficacy, but Phase II and III trials are needed before this becomes a standard treatment option.
Limitations to Keep in Mind
The sample size was small (21 evaluable Hodgkin patients in the expansion phase). This was an open-label, single-arm study without randomization or a control group. Follow-up was relatively short, and the study was conducted in China, where patient populations and healthcare settings may differ from other regions.
A Phase II trial evaluating TQB2618 plus penpulimab in a larger, more diverse Hodgkin lymphoma population is the logical and necessary next step. Researchers are also studying whether biomarkers — such as TIM-3 expression levels on tumor cells — can predict which patients are most likely to respond, moving toward a more personalized approach.