The standard treatment for relapsed/refractory (R/R) classic Hodgkin lymphoma (cHL) is salvage combination chemotherapy, followed by autologous hematopoietic cell transplantation (ASCT) in chemotherapy-sensitive patients. In studies of sequential treatment of , monotherapy with the anti-CD30 antibody-drug conjugate (ADC) ibtuximab (BV) as an initial salvage measure improved the survival rate before ASCT in 27%-43% of patients. Achieve complete response (CR) without chemotherapy. Nivolumab (Nivo) is an anti-PD-1 antibody that restores a potent anti-tumor immune response and is tolerable and effective in patients with R/R cHL. As a salvage treatment for R/R cHL, can Nivo bring more benefits to patients? This was studied in a multi-centre Phase 2 trial and the results were published in the journal Blood. This article compiles and organizes the research for the benefit of readers.
Study Methods
The purpose of this study was to evaluate PET adapted sequential Nivo, or Nivo in combination with ifosfamide , carboplatin and etoposide (NICE) as first salvage therapy for R/R cHL Effect.
The main inclusion criteria are
age ≥18 years old, weight more than 40kg, histology confirmed CD30+cHL and refractory to initial treatment or relapse after initial treatment. Patients with recent myocardial infarction, congestive heart failure, uncontrolled angina pectoris or uncontrolled acute arrhythmia were excluded.
Treatment Methods
Patients received 240mg Nivo intravenously for 3 cycles (14 days/cycle). After completion, PET-CT was performed to evaluate the disease response, and the results determined subsequent treatment (Figure 1). Patients with CR or partial response (PR) received another 3 cycles (total 6 cycles) of Nivo before undergoing PET-CT evaluation, and those evaluated as CR continued with ASCT. Patients who develop progressive disease (PD) after 3 or 6 cycles of Nivo continue to receive 2 cycles (21 days/cycle) of NICE: Nivo 240mg (Day 1), etoposide 100mg/ m2 intravenously (days 1-3), carboplatin AUC 5 (max 750 mg) intravenously (day 2), ifosfamide 5000 mg/m2 intravenously (day 2). Patients with stable disease (SD) after 3 cycles of Nivo treatment can continue to take another 3 cycles of Nivo, or continue to take NICE at the discretion of the treating investigator. Patients who develop SD or PR after 6 cycles of Nivo treatment receive NICE treatment. After NICE treatment, patients with PR or CR can continue to undergo ASCT, while patients with SD or PD will withdraw from the study.
Figure 1 Treatment plan and patient response data
Study endpoints
The primary endpoint is CR status and toxicity at the end of treatment.
Study results
3 patients were enrolled and received study treatment (Table 1), 26 patients were male (60%), and the median age was 35 years (18-70 years). All 43 patients were evaluable for safety, 42 patients were evaluable for response and efficacy, and a total of 38 (88%) patients completed all expected regimen treatments. Table 1 Patient baseline characteristics
Safety
Nivo monotherapy (43 patients) The most common adverse events (AE) were as follows: fatigue (33%), macular rash (19%), arthralgia (16%), pyrexia ( 16%), nausea (16%), leukopenia (16%) (Table 2).
Table 2 The most common adverse events related to Nivo monotherapy
Among the 9 patients treated with NICE, no unacceptable toxicity was found. The most common related adverse events were nausea (78%) and anemia (67%). , ALT elevation (56%), fatigue (56%), vomiting (56%) (Table 3).
Table 3 The most common adverse events associated with NICE
Effectiveness
Among 42 evaluable patients, the objective response rate (ORR) and CR rate after 3 cycles of Nivo were 88% (37/42) and 62%, respectively. (26/42). 37 patients continued to receive 3 additional cycles of Nivo, and the ORR and CR rates after completing 6 cycles were 89% (33/37) and 78% (29/37), respectively. Four patients developed PD after completing 6 Nivo cycles. The endpoint ORR and CR rates of Nivo among 42 evaluable patients were 81% (34/42) and 71% (30/42), respectively. Of the nine patients treated with NICE, all responded, with eight (89%) achieving CR.At the end of all regimens, the ORR and CR rates of evaluable patients were 93% (39/42) and 91% (38/42), respectively. The ORR and CR rates for all treated patients were 91% and 88%, respectively (Table 4).
Table 4 Treatment effect
Survival results
The median follow-up time was 30.7 months. The 2-year progression-free survival (PFS) and overall survival (OS) rates for all treated patients (n=43) were 72% (95% CI: 56-83) and 95% (95% CI: 82-82), respectively. 99) (Figure 2). The 2-year PFS rate for primary refractory patients (n=19) was 79% (95% CI: 53-92), while the 2-year PFS rate for relapsed patients (n=24) was 67% (95% CI :44-82).
Figure 2 Survival results
Transplantation results
Among the 33 patients who underwent ASCT directly after protocol treatment (Nivo/NICE), all patients were in CR status at the time of ASCT, and the PFS and OS rates 2 years after receiving ASCT were respectively 94% (95%CI: 77-98) and 97% (95%CI: 80-99.6). For patients with primary refractory disease (n = 16) and patients who relapsed after first-line therapy (n = 16), the 2-year PFS rate after ASCT was 94% (95% CI: 63-99). The 2-year PFS rates were 96% (95%CI: 76-99) and 86% (95%CI: 33-98) for patients taking Nivo alone before ASCT (n=25) and NICE (n=7), respectively. . The 2-year PFS rate of patients who received consolidation therapy was 91% (95% CI: 69-98); the 2-year PFS rate of patients who did not receive consolidation therapy was 100%.
Non-transplantation results
Four patients declined ASCT after achieving CR, with a median time to final progression of 7.5 months.
Study Conclusions
PET-conformed sequential salvage therapy with Nivo/NICE was well tolerated and effective, with a high rate of CR and enabled transition to ASCT without chemotherapy in most patients.
References
Matthew G. Mei, Hun Ju Lee, Joycelynne M. Palmer, et al. Response-adapted anti-PD-1–based salvage therapy for Hodgkin lymphoma with nivolumab alone or in combination with ICE. Blood. 2022; 139 ( 25): 3605–3616.
Editor: XYkwong
Reviewer: Quinta
Typesetting: Quinta
Execution: Wenting
