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Anti–PD-1/PD-L1 Rechallenge After Immune-Related Adverse Events


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In a study reported in JAMA Oncology, Olivier Lambotte, MD, PhD, found that rechallenge with an immune checkpoint inhibitor after occurrence of immune-related adverse events was associated with occurrence of an immune-related adverse event in approximately half of patients, with no increase in severity.

Olivier Lambotte, MD, PhD

Olivier Lambotte, MD, PhD

Study Details

The study involved 93 consecutive patients referred to the ImmunoTOX assessment board at Gustave Roussy between August 2015 and December 2017. Patients had experienced grade ≥ 2 immune-related adverse events while receiving monotherapy with a programmed cell death protein 1 (PD-1) or programmed cell death ligand 1 (PD-L1) inhibitor. The main outcome measure was the incidence of another immune-related adverse event in patients readministered the same immune checkpoint inhibitor.

Among the 93 patients, median age was 62.5 years and 52% were female. Cancer types included melanoma (33%), lung (16%), colorectal (9%), and lymphoma (9%). The initial immune-related adverse events consisted of 43 grade 2 events (46%), 36 grade 3 events (39%), and 14 grade 4 events (15%); these were primarily hepatitis (18%), skin toxicity (15%), pneumonitis (14%), colitis (12%), and arthralgia (7.5%).

Immune-Related Adverse Events After Rechallenge

Forty patients (43%) were rechallenged with the same PD-1 or PD-L1 inhibitor. The rechallenged and nonrechallenged groups did not differ in terms of median age, time to initial immune-related adverse event, immune-related adverse event severity, or steroid use (42.5% vs 60%, P = .09).

With median follow-up of 14 months, the same or a different immune-related adverse event occurred in 22 (55%) of 40 rechallenged patients, with 17 (42.5%) experiencing a recurrence of the same type of immune-related adverse event and 5 (12.5%) experiencing a different type (4 experienced both a recurrence and a different type of immune-related adverse event). Recurrences affected the same organs involved in the initial immune-related adverse event; frequency of recurrence differed, with recurrence of arthralgia in five of six patients, grade 4 neutropenia in two of three, colitis in three of five, skin toxicity in three of seven, hepatitis in three of five, pneumonitis in one of five, and lipase elevation in zero of three. Second immune-related adverse events were not more severe than initial immune-related adverse events, with 38% being grade 2, 48% grade 3, and 14% grade 4. Median time to the initial immune-related adverse event was shorter among patients who experienced a second immune-related adverse event vs those who did not (9 vs 15 weeks, P = .04).

The investigators concluded, “The risk-reward ratio for an anti–PD-1 or anti–PD-L1 rechallenge appears to be acceptable, although these patients require close monitoring; further investigation into rechallenge conditions through a prospective clinical trial is needed.” ■

Simonaggio A, et al: JAMA Oncol. June 6, 2019 (early release online).


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