Blood cancers

Checkpoint inhibitors may sensitise patients with refractory NHL to improve responses

Checkpoint inhibitors may help sensitise relapsed/refractory non-Hodgkin lymphoma (NHL) to subsequent chemotherapy, according to US researchers.

The retrospective study analysed data from 59 patients who received checkpoint blockade as a second or later line therapy between 2012 and 2017 and subsequently received systemic therapy due to disease progression.

Lymphoma subtypes were mostly DLBCL (40%), follicular lymphoma (22%) and DLBCL transformed from an indolent lymphoma (8%).

Patients had a median age of 62 years and had received a median of three previous therapies. Most (54%) had experienced some response to their last therapy and relapsed, although 44% had not had any response.

The study found patients treated with nivolumab, pembrolizumab, cemiplimab, durvalumab and ipilimumab/nivolumab in combination had an overall response rate of 8.5%.

However their response to a subsequent chemotherapy regime was a more impressive 51%.

Responses were seen irrespective of NHL subtype, chemotherapy regimen and earlier response to checkpoint blockade therapy.

The study found an additional 17% of patients were able to achieve stable disease, for a clinical benefit rate of 68%.

“Achievement of stable disease may itself be a milestone for these patients, as the median survival for patients with DLBCL who have failed ASCT is 57–126 months,” the study authors said.

Commenting on the study, Professor Judith Trotman told the limbic the study provided promising data which supported the hypothesis that checkpoint inhibition could sensitise patients with refractory NHL to subsequent chemotherapy.

“Certainly the median 310 day duration of response for patients achieving at least stable disease is very encouraging and prospective studies of careful sequential approaches are warranted,” she said.

“An Australian Phase I study (the AvR-CHOP study) has demonstrated the safe deliverability of such an approach in the first line setting for DLBCL and the feasibility of a larger randomised Phase II/III study is now being evaluated by the ALLG lymphoma lead, Associate Professor Eliza Hawkes.”

“Such prospective studies while aimed for synergistic “immunogenic” cell death would warrant close monitoring of both toxicity and futility,” she added.

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