OUTLOOK

Lymphoma: 4 big questions

Numerous treatment options have emerged for lymphomas, but there are still considerable challenges to be tackled to increase the chances of long-term survival.
Michael Eisenstein is a freelance science writer in Philadelphia, Pennsylvania.

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Credit: Ana Kova

1. Will immunotherapy rewrite the prognosis for recurrent lymphoma?

Why it matters

For many patients, first-line treatment buys little or no relief, and relapsed or refractory disease entails more-intensive treatment and a worse outlook. Therapies that reprogram immune cells to attack cancer could deliver longer-lasting recovery.

What we know

Two chimeric antigen receptor T-cell therapies (CAR-T therapies) are available for certain non-Hodgkin’s lymphomas. Last year, a trial reported that more than half of the participants achieved complete remission, with at least one still cancer-free two years on.

Next steps

Dozens of trials of CAR-T therapy for B-cell lymphomas are underway. Some are exploring alternative targeting approaches to adapt the treatment to different forms of the disease. Others aspire to mitigate toxic side effects.

2. Can real-time monitoring help oncologists stay a step ahead in lymphoma treatment?

Why it matters

Clinicians need to understand the nature and extent of a patient’s cancer to manage treatment, but existing tools have limitations. Biopsies are invasive and offer a limited view of the tumour, whereas imaging can generate false positives and requires repeated radiation exposure.

What we know

At least three studies indicate that monitoring circulating tumour DNA (ctDNA) in blood might be a powerful complement to imaging in terms of assessing treatment efficacy for diffuse large B-cell lymphoma. And ctDNA levels could give an early indication of disease recurrence.

Next steps

Researchers have obtained promising preliminary results for ctDNA-based methods in Hodgkin’s lymphoma and other diseases. But the accuracy of such assays needs to be carefully validated before they can reach the clinic.

3. How can treatment of early-stage Hodgkin’s lymphoma be tweaked to improve long-term outcomes?

Why it matters

The standard therapy, in which patients receive multiple rounds of chemo- and radiotherapy, delivers excellent cure rates for Hodgkin’s lymphoma. But survivors face a heightened risk of complications such as heart disease and further malignancies in the decades that follow.

What we know

Radiotherapy is a major source of toxicity. Some studies indicate that forgoing it might not meaningfully reduce overall survival in early-stage disease, possibly because of a reduced chance of death from treatment-related causes — but some such studies used outdated regimens.

Next steps

It might be possible to identify which patients will benefit the most from chemotherapy alone. Trials are also exploring whether some second-line treatments might make safer first-line treatments.

4. Can allogeneic stem-cell transplantation be made safer?

Why it matters

Stem-cell transplantation is a last resort for recurrent lymphoma. Patients who are ineligible for transplantation with their own stem cells must receive cells from a donor — but there is a high risk that they could develop graft-versus-host disease (GvHD).

What we know

Chronic GvHD is a major cause of mortality. But the 2017 approval of ibrutinib, which blocks production of GvHD-exacerbating B cells, has shown that it’s possible to make transplantation safer. Other therapies in development might make transplantation more attractive.

Next steps

Studies suggest that the infusion of regulatory T cells derived from umbilical cord blood can limit rejection in transplant recipients. Scientists are exploring whether such infusions can prevent GvHD.

Nature 563, S55 (2018)

doi: 10.1038/d41586-018-07367-0

This article is part of Nature Outlook: Lymphoma, an editorially independent supplement produced with the financial support of third parties. About this content.

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