ASH 2024 | Outcomes of Hodgkin lymphoma transformation in the modern era of therapy

Transformation in CLL is the development of an aggressive lymphoma, most commonly diffuse large B-cell lymphoma. This is a rare event overall. Hodgkin lymphoma transformation is an uncommon clinical and histologic form of that event. In the setting of transformation, prior CLL-directed therapy has been shown to be prognostic, associated with survival outcomes, certainly in the setting of large-cell lymphoma, but also in earlier reports in the setting of Hodgkin transformation, specifically with purine nucleoside analog therapy. So as the treatment paradigm for CLL has evolved, namely now incorporating small molecule inhibitors of BTK inhibitors, BCL2 inhibitors, the aim of this study was to look at the outcomes of patients with Hodgkin lymphoma transformation of CLL/SLL in a current therapeutic era. 

So being this is a rare event, this required a lot of collaboration and so this was a multi-center retrospective study across 12 institutions. We pulled a subgroup of patients with Hodgkin transformations with 41 patients which represented about 10 percent of this larger cohort of a little over 400 patients with transformation of CLL that Dr Kittai had presented the large cell lymphoma subgroup on last year. We subdivided that group into patients with concurrent Hodgkin transformation, meaning diagnosed within three months, a group where they had no prior CLL therapy, so diagnosed later than three months after the CLL diagnosis with Hodgkin transformation, but had received no interval therapy, and then patients with prior CLL-directed therapy, which was not chemotherapy, and that was antecedent to their Hodgkin transformation diagnosis, that was 19 patients of the subgroup, and that was predominantly BTK inhibitor therapy. And amongst those 19 patients, the majority of them were on BTK inhibitor at the time of their Hodgkin transformation event. 

What we saw in presentation across these was that it looked similar in clinical presentation, meaning largest node size and LDH and SUV max on PET-CT. So the presentation looked similar amongst these subgroups of concurrent no prior therapy and prior non-chemotherapy. And actually we did not see a significant difference in the outcome. So these patients were treated in a contemporary Hodgkin lymphoma fashion. So most patients either got ABVD or brentuximab vedotin and AVD, so contemporary treatment and Hodgkin-directed treatment, which is an important part. Of the patients who received at least one additional line of therapy, that was 11 patients. All of them received either brentuximab vedotin or an immune checkpoint inhibitor or both. So really contemporary Hodgkin-directed therapies as well. The overall response rate to first-line therapy was a little over three quarters and two-thirds being the CR rate or a little bit better. With around three years of median follow-up, the median overall survival, or the three-year OS rate, I should say, was actually still encouraging, but still worse than you would probably expect for a de novo Hodgkin with no prior CLL in a similar older patient population. 

But I think the main takeaway here is that the prior treatment therapy in this cohort with just prior small molecule inhibitor treatment did not seem to impact outcomes. And these patients do relatively well with Hodgkin-directed treatment. So in the past, there had been some debate on whether or not to treat them with CLL-directed therapies. I think this lends further support to these patients should be treated with Hodgkin-directed therapies. In 2024, now 2025, for me, that’s going to be the NIVO AVD likely based on the SWOG 1826 data which you know included that particular benefit in older patients which will be enriched for in a CLL Hodgkin transformation group.

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