Initial phase 1 trials including CheckMate-039 and KEYNOTE-013 showed promising results: in one study, nivolumab showed an investigator-assessed overall response rate (ORR) of 87% and a complete response (CR) rate of 17% in 23 patients with relapsed/refractory cHL.2-4 For KEYNOTE-087, researchers evaluated pembrolizumab in 210 patients with relapsed/refractory cHL and found an ORR of 69% and a CR rate of 22.4%. Higher PD-L1 levels were associated with higher response rates with both drugs.


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Merryman et al noted that the most common adverse events reported in checkpoint blockade studies are diarrhea, fever, fatigue, infusion reactions, nausea, pruritus, rash, and hypothyroidism, with somewhere between 4% and 6% of patients discontinuing use because of toxicity.

In NHLs, a common genetic abnormality has not yet been found that could be used to determine sensitivity to checkpoint blockade. Primary mediastinal B-cell lymphoma, however, has several overlaps with cHL in its histologic and genetic features, including frequent genetic abnormalities at 9p24.1.

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Dr Kahl added that primary central nervous system lymphoma and primary testicular lymphoma are 2 types where there “might be more activity that results in increased PD-1 ligand expression,” which gives a better rationale to use checkpoint blockades in those entities.

He added that several ongoing studies are evaluating the efficacy and safety of conventional therapies combined with checkpoint inhibitors as compared with traditional therapies alone to determine whether outcomes can be improved.6-10

Yet at this point, “there is really no role for checkpoint inhibitors as a front-line management in NHL,” Dr Kahl said. “There are studies, but they are in their infancy and not ready for prime time yet.”

References

  1. Merryman RW, Armand P, Wright KT, Rodig SJ. Checkpoint blockade in Hodgkin and non-Hodgkin lymphoma. Blood Adv. 2017;1(26):2643-54. doi: 10.1182/bloodadvances.2017012534
  2. Asnell S, Gutierrez ME, Shipp MA, et al. A phase 1 study of nivolumab in combination with ipilimumab for relapsed or refractory hematologic malignancies (CheckMate 039). Blood. 2016;128(22):183.
  3. Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372(4):311-9.
  4. Zinzani PL, Ribrag V, Moskowitz CH, et al. Phase 1b study of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma: results from the ongoing Keynote-013 trial. Blood. 2016:128;22:619.
  5. Chen R, Zinzani PL, Fanale MA, et al. Phase II study of the efficacy and safety of pembrolizumab for relapsed/refractory classic Hodgkin lymphoma. J Clin Oncol. 2017;35(19):2125-32. doi: 10.1200/JCO.2016.72.1316
  6. ClinicalTrials.gov. Pembrolizumab after ASCT for Hodgkin lymphoma, DLBCL and T-NHL. NCT02362997. https://clinicaltrials.gov/ct2/show/NCT02362997. Accessed February 2018.
  7. ClinicalTrials.gov. Nivolumab, ifosfamide, carboplatin, and etoposide as second-line therapy in treating patients with refractory or relapsed Hodgkin lymphoma. NCT03016871. https://clinicaltrials.gov/ct2/show/NCT03016871. Accessed February 2018.
  8. ClinicalTrials.gov. Nivolumab and lenalidomide in treating patients with relapsed or refractory non-Hodgkin or Hodgkin lymphoma. NCT03015896. https://clinicaltrials.gov/ct2/show/NCT03015896. Accessed February 2018.
  9. ClinicalTrials.gov. Study of pembrolizumab (MK-3475) vs brentuximab vedotin in participants with relapsed or refractory classic Hodgkin lymphoma (MK-3475-204/KEYNOTE-204). NCT02684292. https://clinicaltrials.gov/ct2/show/NCT02684292. Accessed February 2018.
  10. ClinicalTrials.gov. Pembrolizumab and ibrutinib in treating patients with relapsed or refractory non-Hodgkin lymphoma. NCT02950220. https://clinicaltrials.gov/ct2/show/NCT02950220. Accessed February 2018.