5-year follow-up trial of nivolumab in R/R classical Hodgkin lymphoma: CheckMate 205

Patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL) have a poor prognosis after an initial treatment with autologous hematopoietic stem cell transplant (auto-HSCT) with an overall survival (OS) of approximately 2 years. Initial data from the CheckMate 205 (NCT02181738) trial demonstrated good efficacy and safety with nivolumab after auto-HSCT. The Lymphoma Hub has previously summarized 2-year follow-up data from the CheckMate 205 trial. Below, we present the extended 5-year follow-up data to understand long-term outcomes after nivolumab administration.

Study design

This is a phase II trial of nivolumab in patients with R/R cHL who had failed previous treatment with auto-HSCT. Full details of the study design are previously summarized on the Lymphoma Hub. Eligible patients were:

• aged ≥ 18 years;
• diagnosed with cHL and failed treatment with auto-HSCT;
• grouped according to prior treatment with brentuximab vedotin (BV): BV naïve (cohort A), received BV after auto-HSCT failure (cohort B) or received BV before/after auto-HSCT (cohort C).

The primary endpoint was the objective response rate. Secondary endpoints included duration of response, complete remission (CR), partial remission rate and duration of CR and partial remission. Exploratory endpoints included progression-free survival, best overall response  OS, and safety.

Results

Efficacy

In total, 243 patients were treated in cohort A (n = 63), cohort B (n = 80) and cohort C (n = 100). At a median follow-up of 58.5 months:

• A total of 58 patients received subsequent allogeneic HSCT, with the highest proportion of patients in cohort C (Table 1).
• Median OS was not reached in any cohort.
• The 2-year OS rate was 87.1% (95% CI, 82–90.8) and the 5-year OS rate was 71.4% (95% CI, 64.8–77.1).

Table 1. Responses between cohorts A, B and C.*

Auto-HSCT, autologous stem hematopoietic cell transplantation; BOR, best overall response; BV, brentuximab vedotin; CR, complete remission; DoR, duration of response; ORR, objective response rate; PD, progressive disease; PR, partial remission; SD, stable disease.  *Adapted from Ansell SM, et al.1
Response, % (unless otherwise stated)	Cohort A (BV-naive) (n = 63)	Cohort B (BV after auto-HSCT) (n = 80)	Cohort C (BV before and/or after auto-HSCT) (n = 100)	Overall (N=243)
ORR	65.1	71.3	71.2	71.2
BOR
CR	31.7	13.8	21	21.4
PR	33.3	57.5	54	49.8
SD	22.2	17.5	12	16.5
PD	12.7	8.8	11	10.7
Median time to response, months	2.0	2.2	2.1	2.1
Median time to CR, months	3.9	4.4	4.2	4.0
Median DoR, months	26.2	16.6	18.2	18.2
Received subsequent allogeneic HCT	22.4	24.1	51.7	23.9

Safety

• Treatment related adverse events (TRAEs) occurred in 81.5% of patients and 27.6% were classed as Grade 3–4.

• The most common TRAEs (occurring in ≥10% patients) were fatigue, diarrhea, infusion-related reaction, rash, nausea, pruritus (Figure 1).
• In total, 22 patients discontinued treatment due to TRAEs and 13 patients due to Grade 3–4 TRAEs, with pneumonitis being the most common adverse event leading to discontinuation (2.9%).
• There were no deaths reported.

TRAEs, treatment related adverse events.
*Adapted from Ansell SM, et al.¹

Conclusion

The 5-year follow-up data from CheckMate 205 trial are consistent with the previously reported 18 and 33 months results. Nivolumab showed durable outcomes in patients with cHL who were R/R after auto-HSCT, and no new safety signals were identified. This study also provides evidence that patients may discontinue treatment one year after CR and restart treatment if cHL progresses.