A Retrospective Look at Drug Sensitivity Before and After Checkpoint Blockade in R/R NHL

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Checkpoint-based therapies may sensitize patients to subsequent therapies.
Checkpoint-based therapies may sensitize patients to subsequent therapies.
The following article features coverage from the American Society of Hematology (ASH) 2018 meeting. Click here to read more of Cancer Therapy Advisor's conference coverage.

SAN DIEGO — In patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL) who had already received multiple prior lines of therapy, response rates to subsequent therapeutic interventions in the salvage setting — administered sequentially after treatment with checkpoint blockade therapies (CBTs) — were determined not to influence survival outcomes. And, noted the investigators of the study during a presentation at the 2018 American Society of Hematology (ASH) Annual Meeting, in San Diego, California, “there is no significant evidence that post-CBT treatment response and post-CBT regimens are associated.”1

Despite reaching this conclusion, the investigators still revealed that in many patients the post-CBT treatment response with or without stem cell therapy (SCT) were of a significantly greater duration than their pre-CBT duration of response (DOR; 1 month vs 4.6 months).

The researchers, who collaborated across 17 centers across the United States and Canada, were curious to see if checkpoint inhibition in this population would prime patients to be more sensitive to subsequent medications, helping improve outcomes in a synergistic manner. Because checkpoint therapies have little single-agent activity in R/R NHL, the investigators sought to retrospectively identify which drugs, if any, appeared to work particularly well post-CBT treatment in patients who later discontinued CBT due to progression of disease (PD) or toxicity.

Patients were included if they had had prior frontline chemotherapy, treatment with checkpoint inhibitors between 2012 and 2018, and had received therapy subsequent to checkpoint inhibition.

The R/R NHL patient population that was analyzed was strikingly heterogeneous. Survival data were stratified by post-CBT treatment regimen categories and histologic subgroups, and encompassed 59 evaluable patients representing 11 histologic subtypes. Notably, said presenter Nicole Carreau, MD, New York University Langone Health, New York, New York, at least 1 patient within every single subtype had a response to additional therapies after receiving checkpoint inhibitors.

Prior to being treated with checkpoint inhibitors, the median number of prior treatments among patients was 3 (range 1-9), and the median duration of response to the treatment given immediately prior to CBT was 35 days.

Responses to subsequent treatment after treatment with checkpoint inhibition across the patient population yielded 19 partial responses (PRs, 32%), 10 patients who had stable disease (SD, 17%), and 19 who experienced disease progression (32%). A variety of post-CBT treatment regimens were tried: standard chemotherapy (49%), targeted therapy (32%), and the use of clinical trial drugs (17%). The overall response rate (ORR) to post-CBT treatment was 51%, with 11 (19%) participants demonstrating a complete response and 19 (32%) with partial responses.

Four out of 5 patients who had a complete or partial response to treatment before checkpoint blockade had a complete or partial response to treatment after checkpoint inhibition, and 26 out of 54 patients who experienced stable disease or progression after being treated with checkpoint inhibitors had a partial or complete response to other therapies after that.

Median overall survival was 2.1 years; median progression-free survival was 6.3 months. Dr Carreau said her team concluded that overall survival with post-checkpoint therapy “was independent of the treatment regimen, but many of these treatments bridged patients to SCT.”

The researchers concluded that even if patients do not respond to treatment with checkpoint inhibitors, or their disease progresses, the checkpoint-based therapies they received may sensitize them to subsequent therapies.

Despite the fact that no revelations came from the study on the specific drug order or drug treatment type that would be optimal following checkpoint inhibition in R/R NHL, the scientists still concluded that treatment with checkpoint blockade medications followed by SCT could be a novel treatment approach for patients who are ineligible for SCT or chimeric antigen T-cell receptor (CAR-T) cell therapy.

“This may inform the optimal sequencing of second-line therapies and beyond, because if [these] data do pan out, we may want to try moving immunotherapy earlier to the frontline,” she added.

When asked by an audience member about what mechanisms were at play that likely dictated response to checkpoint inhibitors, Dr Carreau said: “We know that immunotherapy does stay in your body for quite a long time, even after you stop receiving the therapy,” and treatments like chemotherapy may induce more mutations and increase tumor mutational burden (TMB); increased TMB does influence response to checkpoint inhibitors. She warned that this was just a hypothesis, however.

Disclosure: The presenters have disclosed financial ties to various pharmaceutical companies. For a full list of disclosures, please see the original abstract.

Read more of Cancer Therapy Advisor's coverage of the ASH 2018 meeting by visiting the conference page.

Reference

1. Carreau NA, Pail O, Armand P, et al. Checkpoint blockade therapy may sensitize aggressive and indolent non-Hodgkin lymphoma to subsequent therapy. Oral presentation at: American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA. Abstract 93.

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