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Letters to the Editor
Efficacy of anti-PD1 re-treatment in patients with Hodgkin lymphoma who relapsed after anti-PD1 discontinuation
Patients with relapsed/refractory Hodgkin lymphoma (R/R HL) experience high response rates upon anti-PD1 therapy. In these patients, there is limited data about the optimal duration of treatment and the risk of relapse after anti-PD1 discontinuation. We have previously reported the outcome of 11 patients with R/R HL who discontinued anti-PD1 therapy after achieving a com- plete response (CR) upon nivolumab.1 These patients experienced a favorable outcome as only two of them had relapsed after a median follow-up of 21.2 months from discontinuation. Despite the low relapse rate observed in that study, physicians may be worried about the possibility to further rescue these heavily pre- treated patients in case of relapse after anti-PD1 discon- tinuation. Notably, it is still unknown whether these patients will remain sensitive to a second course of anti- PD1.
Here, we investigated the efficacy of anti-PD1 re- treatment in patients that were initially sensitive to anti-PD1 therapy but who relapsed after anti-PD1 dis- continuation.
We retrospectively analyzed patients with R/R HL who experienced a partial (PR) or CR upon anti-PD1 monotherapy and discontinued the treatment either because of unacceptable toxicity or due to prolonged remission, based on the physician’s decision. Patients who discontinued anti-PD1 therapy because of relapse/progression or underwent consolidation with allogenic stem cell transplantation (alloSCT) were not included. Patients meeting the eligibility criteria were identified through the French lymphoma network (LYSA).
We identified seven patients who met the inclusion criteria. Their characteristics are summarized in Table 1. At anti-PD1 initiation, most patients presented with advanced disease (five of them had Ann Arbor stage III/IV) and had been heavily pre-treated (median num- ber of prior systemic lines =6, seven had received prior brentuximab vedotin, five prior autologous stem cell transplantation (SCT) and two prior allogenic SCT). Overall, anti-PD1 was discontinued after a median duration of 11.4 months (range: 0–26.7) and a median of 23 infusions (range: 1–51). Anti-PD1 was discontinued because of prolonged remission (n=5) or toxicity (n=2, patient 5 had experienced grade 4 acute liver graft-ver- sus-host-disease [aGvHD] and patient 7 grade 3 laryn- geal tightness). The disease status at anti-PD1 discontin- uation was CR for six patients and PR for one patient. The median time to relapse after anti-PD1 discontinua- tion was 12.1 months (range: 5.3–26.7). All patients were re-treated with the same anti-PD1 antibody as ini- tially administered (six with nivolumab and one with pembrolizumab).
All patients responded to anti-PD1 re-treatment (Figure 1). The best response was CR for four patients and PR for three patients. At the time of analysis (medi- an follow-up of 19.2 months from anti-PD1 re-treat- ment), 4 of 7 patients have ongoing responses to anti- PD1 monotherapy, three of them beyond 12 months. Interestingly, three patients discontinued anti-PD1 treatment after achieving a second objective response upon anti-PD1 re-treatment (patients 3, 5 and 7). Patient 3 discontinued anti-PD1 treatment a second time due to hyper-eosinophilia and then relapsed 2
Table 1. Patients’ characteristics at anti-PD1 initiation. Patients’ characteristics
Age, median, years (range)
Sex, male, number (%) cHL subtype, number (%)
Nodular sclerosis HL
Unclassifiable
Performance status (ECOG), No (%)
I/II
III/IV
Prior lines of systemic therapy, median (range)
Prior radiation therapy, number (%)
Prior treatment with Brentuximab Vedotin, number (%) 7 (100)
N=7
47 (34-71)
2 (28.6)
6 (85.7) 1 (14.3)
5(71.4)
2 (28.6)
5 (71.4) 2 (28.6)
6 (85.7)
1 (14.3)
23 (1-51)
0–1
≥2
Stage disease, number (%)
2 (28.6) 5 (71.4) 6 (4-11) 4 (57.1)
Prior autologous HSCT, number (%) Prior allogenic HSCT, number (%) Anti-PD1, number (%)
Nivolumab
Pembrolizumab
Number of anti-PD1 infusions
during 1st course, median (range)
Duration of 1st course of anti-PD1
therapy (months), median (range)
Best Overall Response to 1st course of anti-PD1, number (%)
CR
PR
Reason for anti-PD1 discontinuation, number (%)
Prolonged response
Toxicity*
Disease status at anti-PD1 discontinuation, number (%)
CR
PR
Time between discontinuation
and relapse (months), median (range) Follow-up from anti-PD1 re-treatment (months), median (range)
Best response to 2nd course of anti-PD1
CR
PR
6 (85.7)
1 (14.3)
5 (71.4) 2 (28.6)
6 (85.7)
1 (14.3) 12.1 (5.3-26.7)
19.2 (4.8-39.9)
4 (57.1)
3 (42.9)
11.4 (0-26.7)
*One grade 4 acute liver graft-versus-host-disease, and one grade 3 laryngeal tight- ness. HL: Hodgkin lymphoma; cHL: chronic Hodgkin lymphoma; CR: complete response; PR: partial response.
months later. Patient 7 tolerated the second course of nivolumab well (notably, there was no recurrence of laryngeal tightness), achieved a PR and discontinued the treatment after 12 months. Unfortunately, he relapsed 5 months later. The patient then received a third course of nivolumab and achieved another PR which is still ongo- ing at 18 months.
Patient 5 had undergone alloSCT prior to anti-PD1 therapy. He discontinued nivolumab after a single infu- sion due to grade 4 liver GvHD. Nevertheless, he achieved a CR which lasted 9 months. At relapse, he
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haematologica | 2020; 105(11)