Sequence of treatment matters in second-line and third-line therapy for a certain type of blood cancer

Illlustration of DNA courtesy Peripheral T-cell lymphomas Consortium (PETAL)

CANCER DIGEST – May 11, 2025 – A new analysis of treatment regimens following the failure of standard therapy for an aggressive and difficult-to-treat form of lymphoma shows that the sequence of subsequent therapies can have a significant impact on outcomes. The results of the analysis were published in the May 1, 2025 British Journal of Hematology.

The researchers led by senior author Salvia Jain, MD of the Massachusetts General Hospital looked at followup treatments for 830 patients with a form of lymphoma called peripheral T cell lymphoma (PTCL), so called because the cancer arises in immune system blood cells, called T cells, which normally fight cancer. In this case, however, the T cells themselves have mutated to grow abnormally in peripheral tissues, such as lymph nodes, spleen, GI tract or skin.

When patients with PTCL fail standard chemotherapy, there is no standardized follow-on treatment regimens. Some physicians try a different chemotherapy, or they add different treatments that aim to interfere with the cell processes the cancer needs to grow. The processes are categorized as epigenetic modifiers or small molecule inhibitors.

In this analysis of different approaches to second or third treatment regimens, the researchers compared 12 possible sequences of treatment used in second or third line therapies. There were 540 patients treated in second- line regimens and 290 in third-line therapies.

Graphic courtesy of British Journal of Haematology (click to enlarge)

In a complex diagram tracking treatment sequences and outcomes, the study analysis showed that using small molecule inhibitors such as Gleevec® or Tarceva® as second-line therapies followed by epigenetic modifiers such as Zolinza® or Vidaza® significantly improved survival compare to other sequences of treatment.

“These results support the earlier use of these novel therapies, prioritize further research of these drug classes, and provide a framework for examining survival effects with sequential treatments in other cancers,” said Sorial in a press release. “They also highlight that targeted signaling inhibitors like duvelisib warrant ongoing clinical investigation in this patient population with limited treatment options.”

Sources: Massachusetts General Hospital press release and British Journal of Hematology