Salvage chemotherapy after failure of PD-1 inhibitor therapy is effective in improving outcomes in patients with R/R cHL

Classic Hodgkin lymphoma (cHL) is one of the most common malignancies in adolescents and young adults, and most patients can be cured with standard chemoradiation

Investigators have recently reported significant efficacy of conventional chemotherapy in a small subset of patients with solid tumors that progressed after PD-1 inhibitor therapy, in two small cohorts in France and Italy and in a large multicenter analysis, which were found in relapses.

We retrospectively analyzed the results of a multicenter cohort of chemotherapy-refractory patients who did not respond to PD-1 inhibitors, followed by salvage chemotherapy, and underwent allogeneic hematopoietic stem cell transplantation (allo-SCT).

Inclusion criteria were (1) patients diagnosed with cHL; (2) age ≥18 years; (3) PET-CT confirmed disease progression after treatment with PD-1 inhibitors; (4) Eastern Cooperative Oncology Group performance status score of 0 -1 point

1 Patient characteristics

From March 2017 to November 2020, 28 patients with cHL who were refractory to PD-1 inhibitors (n=10, 36%) or had disease progression after initial response (n=18, 64) were enrolled in the study %), the median age at diagnosis was 29 years (range: 19-71), and the baseline characteristics are detailed in Table 1

Table 1 Patient characteristics

2 Patient response to salvage chemotherapy

Disease progression after PD-1 inhibitor therapy was assessed using PET-CT (all patients) and histological assessments were repeated (n=9)

Table 2 Remission before and after CPI treatment

3 Prognosis of allo-SCT in patients

If eligible (n=25), all patients with objective responses received allo-SCT, and only 1 patient received consolidation therapy with autologous hematopoietic stem cell transplantation
.

After starting chemotherapy after CPI failure, after a median follow-up of 21 months, the 2-year OS rate was 80.
0% (95% CI 71.
9-88.
1) and the 2-year PFS rate was 70.
7% (95% CI 61.
0-80.
4) (Figure 1).
)
.

figure 1

Chemotherapy for R/R cHL patients who have failed CPI therapy is an effective and feasible option and offers a potential bridge to allogeneic transplantation
.

The interaction and potential synergistic effects between immunotherapy and chemotherapy have been well documented, and chemotherapy induces cell death, thereby enhancing the exposure of tumor antigens to the immune system
.

The BeGEV regimen is a second-line salvage treatment for cHL, and all patients achieved CR
.

In addition, 2 patients who were resistant to BeGEV prior to CPI therapy overcame chemoresistance
.

Although this finding is limited by the small sample size, the data suggest that this regimen may be considered the first-choice regimen for patients who do not respond to PD-1 inhibitors
.

references:

Calabretta E, Guidetti A, Ricci F, et al.
Chemotherapy after PD-1 inhibitors in relapsed/refractory Hodgkin lymphoma: Outcomes and clonal evolution dynamics.
Br J Haematol.
2022 Jul;198(1):82-92.
doi: 10.
1111 /bjh.
18183.
Epub 2022 Apr 25.

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