Decitabine + Carrelizumab is safe and effective in the treatment of R/R cHL: the latest research results of Professor Han Weidong’s team

Programmed death receptor 1 (PD-1) inhibitor monotherapy is effective for relapsed/refractory classic Hodgkin’s lymphoma (R/R cHL), but some patients are resistant to PD-1 inhibitors, only A few patients achieved lasting remission.

Therefore, there is an urgent need for an effective treatment plan for patients with relapsed/progressive cHL after PD-1 inhibitor monotherapy.

The team of Professor Han Weidong from the Chinese People’s Liberation Army General Hospital recruited 25 patients with R/R cHL who had previously received PD-1 inhibitor treatment into the test cohort, and received decitabine and the PD-1 inhibitor carrelizumab ( camrelizumab), 52% of patients showed objective remission.

Subsequently, the study recruited 26 patients who had previously received PD-1 inhibitor monotherapy into the expansion cohort.

Recently, the results of the follow-up of the extended cohort and the test cohort were published on Clinical Cancer Research.
Yimaitong organizes its main contents as follows for the reference of readers.

Research methods Patients ≥12 years old, with a physical performance score (ECOG PS) of 0 or 1 in the Eastern Cancer Cooperation Group, and with good blood, liver, kidney, lung, and heart functions meet the inclusion criteria.

Patients who have received or have not received PD-1 inhibitor treatment are eligible for inclusion in this study.
This analysis only reports data on patients who have received PD-1 inhibitor monotherapy, including the test cohort (n=25) and Expansion queue (n=26).

Patients receive decitabine (10mg/day, day 1-5 of each cycle) + carrelizumab (200mg/day, day 8 of each cycle) every 3 weeks until the disease progresses or There is intolerable toxicity or the patient decides to withdraw from the group.

Patients with continuous complete remission (CR) ≥ 1 year were discontinued decitabine + carrelizumab treatment and not undergoing transplantation.

Patients with uncertain remission can continue to receive decitabine + carrelizumab treatment for four cycles.
If the imaging evaluation proves that the disease is progressing, the treatment is stopped.

Efficacy evaluation in the intention-to-treat population (ITT).

The primary endpoints of the study include CR rate and safety.

Secondary endpoints include progression-free survival (PFS), duration of remission (DOR), time to remission, and objective response rate (ORR).

Study results From January 1, 2017 to August 31, 2019, 51 patients with R/R cHL who had previously received PD-1 inhibitor monotherapy were enrolled, including 25 patients in the test cohort and 26 patients in the expansion cohort .

The baseline characteristics are shown in Table 1.

Table 1 As of the analysis deadline (September 18, 2020), the median follow-up time for the test cohort was 38.
5 months (range: 26.
9-45.
2 months), and the median follow-up time for the extended cohort was 19.
4 months (range: 3.
2-27.
0 months).

In the test cohort: 17 patients (68%) discontinued treatment (15 cases of disease progression, 1 case of adverse events, 1 case of withdrawal); 4 patients (16%) discontinued decitabine after one year of continuous CR + Carrelizumab treatment and no other treatment before disease progression; 4 patients (16%) are still receiving treatment.

In the extended cohort: 15 patients (58%) stopped treatment (11 cases of disease progression, 1 case of adverse events, 3 cases of withdrawal); 1 patient completed the treatment of decitabine + carrelizumab; 10 Three patients (38%) are still receiving treatment.

All patients underwent safety analysis, and 50 patients completed the efficacy evaluation.

01 Efficacy In the test cohort and the extended cohort, the ORR was 52% (95% CI: 31-72%) and 68% (95% CI: 47-85%).

Nine patients (36%) in the testing cohort and 6 patients (24%) in the expansion cohort achieved CR (Table 2).

Among patients with single-drug resistance to PD-1 inhibitors, the ORRs of the test cohort and the extended cohort were 62% and 80% (CR rates: 46% and 27%), which were higher than those of the primary PD-1 inhibitor Resistant patients (ORR of the test cohort and the extended cohort were 42% and 50%, respectively [CR rate: 25% and 10%]).

Table 2 After ≥1 year of treatment, 4 patients in the test cohort and 2 patients in the extended cohort changed from PR to CR.

At the time of the statistical data cutoff, 7 patients in the test cohort and 10 patients in the expansion cohort were still in remission even if other treatments had not been started (Figure 1A).

For patients with objective remission, the median DOR of the test cohort and the extended cohort were not reached (Figure 1B).

All patients who acquired CR PD-1 inhibitor resistance had a response duration of 93% and 78% at 12 and 24 months, respectively (Figure 1C).

Figure 1 In the test cohort, the median PFS was 20.
0 months (95% CI: 3.
4-36.
6 months), and in the extended cohort it was 21.
6 months (95% CI: 11.
4-31.
8 months) (Figure 2A).

After the two groups of patients were treated with decitabine + carrelizumab, the median PFS of patients who received ASCT was 25.
6 months (95% CI: 11.
2-40.
1 months); the median PFS of patients who did not receive ASCT It was 16.
1 months (95% CI: 2.
7-29.
4 months) (Figure 2B).

About 63% (32/51) of the enrolled patients had longer PFS after decitabine + carrelizumab treatment than the PFS of previous PD-1 inhibitor monotherapy (Figure 2C).

In the test cohort, all 20 patients with CR, PR or SD who were treated with decitabine + carrelizumab had longer PFS than previous PD-1 inhibitor monotherapy (Figure 2C).

The median PFS of patients with primary resistance to PD-1 inhibitor monotherapy treated with decitabine + carrelizumab was 14.
6 months, which was significantly longer than the previous PFS of PD-1 inhibitor monotherapy ( At 4.
7 months, the hazard ratio was 0.
33; 95% CI: 0.
17-0.
66; P<0.
001; Figure 2D). For patients who have achieved CR or PR in previous PD-1 inhibitor therapy, the median PFS obtained by decitabine + carrelizumab is also significantly longer than the median PFS obtained by previous PD-1 inhibitor monotherapy (21.
6 Month vs.
10 months, hazard ratio: 0.
38; 95% CI: 0.
21-0.
70; P = 0.
001; Figure 2E).

Figure 202 Safety Among all 51 patients in the test cohort and the extended cohort, 48 patients (94%) had any grade of treatment-related adverse events (AE; Table 3).

Reactive capillary endothelial cell proliferation is a specific AE of karelizumab, and it is most common in patients who are resistant to PD-1 inhibitors (76%).

Another common treatment-related AE is leukopenia (59%).
After decitabine + carrelizumab treatment, 17 patients (33%) developed grade 3-4 leukopenia.

Table 317 patients (33%) had immune-related AEs.
The most common immune-related AEs were hypothyroidism (8%), myalgia (8%), skin rash (6%) and pneumonia (6%).

Two patients discontinued treatment due to pneumonia (n=1) and hypersensitivity (n=1).

One patient voluntarily withdrew from the trial and subsequently died due to disease progression, and three patients delayed treatment due to grade 3-4 leukopenia.

Research conclusions For R/R cHL patients who have failed single-agent therapy with PD-1 inhibitors, the combination of decitabine and carrelizumab is an effective treatment option with controllable toxicity and high ORR and PFS.

Since sustained remission is only observed in a small number of patients, a phase II study is underway to evaluate PD-1 inhibitors and other epigenetic modification drugs in combination with PD-1 inhibitor-resistant R/R cHL The patient's efficacy.

Reference source: Chunmeng Wang, Yang Liu, Liang Dong, et al.
Efficacy of decitabine plus anti-PD-1 camrelizumab in patients with Hodgkin lymphoma who progressed or relapsed after PD-1 blockade monotherapy.
Clin Cancer Res March 5 2021.
DOI: 10.
1158/1078-0432.
CCR-21-0133.
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