Immuno-oncology agents are effective in treating classic Hodgkin’s lymphoma

Checkpoint inhibitors are effective and well tolerated in patients with refractory or relapsing (r/r) Hodgkin’s lymphoma. Several clinical trials also showed encouraging outcomes in patients with previously untreated, unfavourable Hodgkin’s lymphoma.

Several immuno-oncology agents are being developed for the treatment of classic Hodgkin’s lymphoma (cHL). Dr Marc André (Centre Hospitalier Universitaire UCL Namur, Belgium) discussed their use in r/r disease post-brentuximab vedotin/autologous haematopoietic stem cell transplantation (ASCT) and pre-ASCT, as well as in first-line treatment of advanced and localised cHL [1].

Immuno-oncology agents as first-line treatment

The single-arm, phase 2 CheckMate 205 study (NCT02181738) included a cohort of adults with newly diagnosed, untreated, advanced-stage cHL (n=51) receiving nivolumab as monotherapy (4 doses) followed by a combination therapy with doxorubicin, vinblastine, and dacarbazine (AVD; 12 doses in 6 cycles) [2]. ORR was 69% at the end of monotherapy, 90% after 2 cycles of combination therapy (nivolumab + AVD), and 84% at the end of therapy, with CR reporting at 18%, 51%, and 67%, respectively. Safety results were acceptable, with higher incidences of grade 3 or 4 AEs compared with nivolumab monotherapy, as expected with a combined treatment.

In the same patient population, a single-arm, phase 2 study (NCT03226249) was conducted to evaluate the safety and efficacy of sequential pembrolizumab (3 cycles) and AVD (2–6 cycles; n=30) [3]. This treatment regimen was effective with a 100% estimate of PFS after a median follow-up of 22.5 months. The treatment was well tolerated.

The randomised, open-label, phase 2 NIVAHL study (NCT03004833) was designed to evaluate concomitant treatment with nivolumab + AVD (4 cycles) versus sequential therapy of nivolumab monotherapy (4 cycles), combination therapy (nivolumab + AVD; 2 cycles), and radiotherapy in adults with newly diagnosed, untreated, early-stage, unfavourable cHL (n=109; median age 27 years) [4]. The primary endpoint was CMR after the end of study treatment, which was 90% of patients receiving concomitant treatment and 94% of patients receiving the sequential treatment. One-year PFS was 100% and 98%, respectively. The treatment was well tolerated.

Immuno-oncology agents in r/r disease

Dr André also presented the use of these agents in the treatment of r/r disease [1]. The CheckMate 205 study also assessed nivolumab in brentuximab vedotin-naïve patients (n=63), in patients treated with brentuximab vedotin after ASCT (n=80), and in patients treated with brentuximab vedotin before and/or after ASCT (n=100) [5]. Nivolumab (3 mg/kg) was administered intravenously (i.v.) biweekly until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR), which was 69% (95% CI 63–75), with 16% complete response (CR) and 53% partial response (PR). Safety outcomes were favourable, with grade 3 or 4 neutropenia in 49%, other haematological adverse events (AEs) in 2-10%, and other AEs in 2% of patients.

The single-arm, phase 2 KEYNOTE-087 study (NCT02453594) assessed pembrolizumab (200 mg i.v. every 3 weeks) in patients with r/r cHL [6]. This trial also had 3 cohorts: cohort 1 included patients whose disease progressed after ASCT and brentuximab vedotin treatment (n=69); cohort 2 included patients in whom chemotherapy and brentuximab vedotin had failed (n=81); and cohort 3 included brentuximab vedotin-naïve, post-ASCT patients (n=60). Between 16% and 27.5% of patients completed the 2-year treatment period; discontinuations were due to disease progression, AEs, or CR, which was achieved in 11.6%, 11.1%, and 18.3%, respectively. The primary endpoint was ORR, which was 71.0% (95% CI 64.3–77.0). Of the 58 patients with CR, 38 had no further consolidation therapy, 14 had consolidation therapy without ASCT, and 6 had ASCT. The median duration of response was 16.6 months, progression-free survival (PFS) was 13.6 months. OS was 91.1% after 24 months and 86.4% after 36 months. Safety outcomes were acceptable, and no grade 5 treatment-emerging AEs occurred.

The safety and efficacy of pembrolizumab versus brentuximab vedotin is being evaluated in the randomised, open-label, phase 3 study KEYNOTE-204 (NCT02684292) in patients (n=304) with r/r cHL ineligible for ASCT or relapsing after ASCT [7]. Median PFS was 13.3 months for pembrolizumab and 8.3 months for brentuximab vedotin (HR 0.65; 95% CI 0.48–0.88; P=0.0027).

The use of checkpoint inhibitors before ASCT was tested in a phase 1/2 trial (NCT02572167) using 4 cycles of brentuximab vedotin + nivolumab in patients with r/r cHL who received ASCT per investigator discretion [8]. Results were encouraging: PFS was 77% after 36 months in all patients (n=91) and 91% in the subset that received ASCT after brentuximab vedotin + nivolumab (n=67). OS at 36 months was 93%. Side effects were mild, and only 2 patients discontinued due to AEs.

In conclusion, anti-PD-1 antibodies have become the standard of care in r/r cHL and are safe and effective compounds in first-line treatment. Combination therapies seem to further improve response rates.

1. 
   
   1. André M. Immuno-oncology agents in the treatment landscape of cHL. 3SS16-SL5, EHA 2021 Virtual Congress, 9–17 June.
   2. Ramchandren R, et al. J Clin Oncol. 2019;37(23):1997–2007.
   3. Allen PB, et al. Blood. 2021;137(10):1318–26.
   4. Bröckelmann PJ, et al. JAMA Oncol. 2020;6(6):872–80.
   5. Armand P, et al. J Clin Oncol. 2018;36(14):1428–39.
   6. Chen R, et al. Blood. 2019;134(14):1144-53.
   7. Kuruvilla J, et al. Lancet Oncol. 2021;22(4):512–24.
   8. Advani R, et al. Blood. 2021 DOI: 10.1182/blood.2020009178.

 

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Posted on 5 August 202115 February 2024