Blood cancers

First-line use of polatuzumab in DLBCL down to sub-group interpretation

Use of polatuzumab vedotin as a first-line treatment for diffuse large B cell lymphoma (DLBCL) may depend on which sub-groups of patients show most benefit over time, the British Society for Haematology annual conference has heard.

Several speakers noted there remains a lot to unpick from the Polarix trial of the antibody-drug conjugate targeting CD79b, which reported initial results in January showing improved progression-free survival in patients treated with the modified regimen of pola-R-CHP compared with standard R-CHOP therapy.

The international phase 3 study, which randomised 879 patients, found a 27% reduction in the relative risk of disease progression but at the two-year follow up there was no significant difference in overall survival, explained Dr Graham Collins, consultant haematologist and lymphoma lead at Oxford University Hospitals.

It may be that the difference will become apparent in time, but what has given everyone pause for thought is some “intriguing results” in the sub-group analysis, he said.

“One thing I would emphasise is that the trial was not powered to find a difference in these subgroups. We need to be very careful interpreting but there were some intriguing results.”

Patients seemed to benefit more if they were older, if they had a lack of bulk, if their disease was ABC subtype and if they were men, he said.

Another subgroup of interest was International Prognostic Index (IPI), with the higher IPI subgroup seeming to benefit more than the lower, he told the conference.

The study also showed that patients who achieved a complete response rate with pola-R-CHP were more likely to stay in the disease free group and fewer patients went on to have unplanned additional treatment with polatuzumab.

“Pola-R-CHP does significantly prolong progression-free survival at this interim analysis compared to R-CHOP in patients with intermediate and high risk previously untreated diffuse large B cell lymphoma and the safety profiles of the two regimens are comparable,” Dr Collins said.

He noted that the toxicity between the two groups was similar and it was not a complicated drug to give, but the number needed to treat was 15.

In a separate session on interpreting new trials in diffuse B cell lymphoma, Dr Laurie Sehn, clinical assistant professor in medical oncology at the University of British Columbia and one of the authors of the Polarix study, said improvements in this setting were hugely meaningful as it had been two decades since R-CHOP had become the standard of care.

But she added that there was still much to debate on how to interpret the study.

“We all have a decision to make: do we move pola-R-CHP to our new standard of care? But we have got more trials coming that will serve to add to the confusion,” she said.

“Ultimately I think we need to grapple with what to do with that sub-group analysis and how we might use the data from this trial to improve outcome in our individual cases.”

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