Progress in lymphoma immunotherapy

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In recent years, the effect of immune checkpoint inhibitors on the treatment of Hodgkin’s lymphoma (HL) is impressive, but the disease still needs to be overcome more thoroughly. Mayo Clinic ’s Lymphoma Group Chairman Ansell said that we are learning from the biology of Hodgkin ’s lymphoma and providing more opportunities for the treatment of lymphoma in the future.

We talk about the effectiveness of PD-L1 blockade in HL, looking for deeper solutions, alternative drug combinations that are making progress, and potential pathways for future discovery.

Ansell cited a case of a patient with HL. He called him one night and announced that he was using nivolumab (Opdivo) treatment is effective. In addition to other symptoms, the patient also had enlarged lymph nodes and no more itchy armpits. Sure enough, it turned out that his HL was relieving, but after 2 years of treatment, it did not completely disappear.

As an immunologist, Ansell said he was very disappointed. Obviously, although the treatment was effective, the immune cells did not show enough immune memory. Ansell found another disturbing thing is that it seems that patients must be treated this way throughout their lives.

To review the evidence for nivolumab as a checkpoint treatment, the single-arm phase II CheckMate 205 relapsed / refractory classic Hodgkin lymphoma (cHL) trial, which confirmed the overall response rate (ORR) after a median follow-up of 18 months ) Was 69%, the median duration of response was 16.6 months, and the median progression-free survival was 14.7 months.

The KEYNOTE-087 single-arm phase II study of pembrolizumab (Keytruda) for this disease, in which the ORR of the drug was 69.0%, and the complete remission rate (CR) was 22.4%, 31 patients responded ≥ 6 months.

The Phase I JAVELIN study tested avelumab (Bavencio) as a selective binder for PD-L1 in r / r HL. Ansell pointed out that the ORR of all 31 patients was 41.9% and the partial response was 25.8%. The median reaction time is 1.5 months

This method has been tried by combining immune checkpoint inhibitors nivolumab and ipilimumab (Yervoy). Nivolumab acts as a PD-L1 blocker, ipilimumab targets the immune system to down-regulate the role of CTLA-4. In CheckMate 039, this resulted in an ORR of 74% (n = 23) and a CR rate of 19% (n = 6). At present, immune checkpoint inhibitors have achieved good results in the treatment of cHL, but there is still a long way to go, and we cannot be blindly optimistic.

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