Research in Context

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Pilot study explores radiotherapy plus anti-PD1 in relapsed/refractory multiple myeloma

In this small, exploratory study of heavily pre-treated patients, investigators reported safety and response findings, but say further trials are needed before this approach could inform clinical practice.

  • Mohammad K Khan, MD; Tahseen H Nasti, PhD; Joshua Y Qian, BSc; Troy J Kleber, MD; Jeffrey M Switchenko, PhD; Jonathan L Kaufman, MD; et al.

  • May 23, 2024

  • The Lancet Haematology
  • The Lancet Haematology, Volume 11, Issue 7, Pages e510–e520
  • 10.1016/S2352-3026(24)00105-4

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Evidence before this study

The use of anti-programmed death-1 (anti-PD1) to treat people with relapsed or refractory multiple myeloma has, at times, been hindered due to lack of efficacy and increased toxicity. We did not conduct a formal literature search as, to our knowledge, use of anti-PD1 and radiotherapy has not been studied for people with relapsed or refractory multiple myeloma. However, as a monotherapy in the KEYNOTE-013 trial, anti-PD1 was ineffective for patients with relapsed or refractory multiple myeloma. As a combination therapy with chemotherapy in the KEYNOTE-183 and KEYNOTE 185 trials, anti-PD1 was shown to be extremely toxic for adult patients with multiple myeloma. One prospective study in 2016 used monotherapy nivolumab for people with relapsed or refractory multiple myeloma and showed only one complete response of the 27 patients; this single complete response occurred after salvage radiotherapy was done to a rib plasmacytoma. More than four different solid-tumour mouse models have shown that radiotherapy in combination with anti-PD1 or anti-PD-L1 can improve anti-tumour immunity. The effect of combining radiotherapy with anti-PD1 is unknown for people with multiple myeloma.

Added value of this study

Currently, the use of radiotherapy alone for people with multiple myeloma is limited to palliation of pain, pending fracture, and control of spinal-cord compression. For the combination of radiotherapy with anti-PD1 for people with relapsed or refractory multiple myeloma, clinical and immunological data are needed. Our pilot study responds to this clinically unmet need and advances scientific understanding of the interaction between radiotherapy and anti-PD1 by assessing the safety profile and treatment responses of people with relapsed or refractory multiple myeloma to this combination therapy. The combination was safe and improved objective responses, abscopal responses, and immunological profiles in patients with relapsed or refractory multiple myeloma who had been heavily pre-treated. We also evaluated immunological data and data from after treatment with CAR T cells to help guide future trial designs.

Implications of all the available evidence

Future trials could investigate the use of combining immune-checkpoint inhibitors with radiotherapy as a treatment option for people with relapsed or refractory multiple myeloma or other haematological malignancies. These trials should also include activated CD8+ and CD4+ T cells as potential biomarkers of treatment response. Use of radiotherapy, in combination with immunotherapy, might overcome resistance seen in previous lines of therapy. Government agencies should support clinical trials that include radiotherapy in combination with immunotherapy.

Source: The Lancet Haematology

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