A test for lactate dehydrogenase A activity distinguished sensitive from resistant cells and tumors.

  • Major Finding: In a phase II trial, 30 patients with classic Hodgkin lymphoma had a complete metabolic response.

  • Concept: After a 22.5-month median follow-up period, all patients remained alive with no disease progression.

  • Impact: This study provides support for larger, longer, controlled trials of the combination treatment.

Up to 30% of patients with classic Hodgkin lymphoma (cHL) are not cured by standard-of-care chemotherapy regimens including a combination of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), and bleomycin carries substantial lung toxicity affecting 10% of patients. Based on early clinical trials supporting the use of the PD-1 antibody pembrolizumab as a potential first-line treatment for cHL, Allen and colleagues conducted a multicenter, single-arm, phase II clinical trial of pembrolizumab followed by bleomycin-free (AVD) chemotherapy. The trial enrolled 30 newly diagnosed adult patients with cHL, 12 of whom had early-stage but unfavorable disease and 18 of whom had advanced disease. Thirty-seven percent of patients experienced a complete metabolic response (CMR) after pembrolizumab monotherapy, and all other patients except one had disease reduction. Following completion of pembrolizumab treatment and two cycles of AVD chemotherapy, 100% of patients experienced a CMR. These responses were durable, with no patients requiring subsequent treatment or experiencing disease progression or death after a median follow-up period of 22.5 months (range 14.2–30.6 months); therefore, over the study period, this treatment regimen produced progression-free and overall survival values of 100%. The most common immune-related or adverse events that may have been linked to pembrolizumab treatment included grade 1 rash and grade 1 or 2 infusion-related reaction, and reversible grade 4 Bell's palsy, which may have been immune-mediated, occurred in one patient. Other frequent (occurring in 20% or more of patients) adverse events that may have been attributable to pembrolizumab treatment, all of which were grade 1–2, included anemia, leukopenia, hypertension, and increases in liver enzymes. Limitations of this work include the small sample size, lack of a control arm, and limited follow-up period. In summary, the high rate and long duration of response along with the low frequency of serious adverse events seen in this study indicate that continued investigation of sequential therapy with pembrolizumab and AVD chemotherapy is warranted.

Allen PB, Savas H, Evens AM, Advani R, Palmer B, Pro B, et al. Pembrolizumab followed by AVD in untreated early unfavorable and advanced stage classical Hodgkin lymphoma. Blood 2020 Sep 29 [Epub ahead of print].

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